动脉栓塞微球的研究进展

经导管动脉栓塞术（TACE）已经被用于恶性肿瘤、出血、子宫肌瘤等疾病的治疗,随着影像学技术与设备、材料科学及药物释放技术的发展,越来越多的具备载药、自身可成像或者具备多种功能的微球型栓塞剂被开发出来。文章归纳了一些目前在临床上已经使用的商业化栓塞微球产品,并且总结了微球材料的特点、研究现状、方向和一些在研的有潜在应用价值的栓塞微球及其进展。虽然人们已经研发了许多栓塞微球,但是多数都处于实验室或者小规模实验阶段。目前尚未有一个标准化的方案可以把不同栓塞微球进行横向比较,需要对栓塞微球的载体材料的横向发展与纵向深入、药物的联合使用、对当前药物的改进与新药研发进行更深层次的探索。     

用微球白蛋白栓塞肾动脉的临床观察

为观察人白蛋白微球用于微小动脉栓塞的效果,给进一步的临床应用提供依据。将自行制备的粒径为80-140μm的人白蛋白微球在22只雌性杂种家犬经肾动脉插管注入,致成栓塞,观察在栓塞后不同时间段,肾动脉造影所见和病理变化。结果表明人白蛋白微球可栓塞至肾终末小动脉。在栓塞后14周仍可见微球的存在,未见明显侧枝循环形成。提示可以应用人白蛋白微球有效地进行肾微小动脉的栓塞。     

莪术油明胶微球栓塞犬肝动脉的病理改变

目的 观察莪术油明胶微球栓塞Beagle犬肝动脉后的病理改变,为临床实验提供依据。方法 Beagle犬随机分为生理盐水组(10ml/kg)、空白微球组(15mg／kg)、莪术油微球低剂量组(7．5mg／kg)和莪术油微球高剂量组(15mg／kg),每4周经肝动脉给药1次,连续给药3次,停药后观察4周。观察肝病理组织学改变。结果 明胶微球肝动脉栓塞可致肝组织不可逆性损伤,高剂量组广泛全小叶坏死,低剂量组灶性坏死,空白微球组改变类似高剂量组,生理盐水组未见肝组织损伤。结论 莪术油微球重复经Beagle犬肝动脉给药,可因肝动脉栓塞造成肝脏不可逆性缺血坏死。     

莪术油明胶微球栓塞犬肝动脉的病理改变

目的观察莪术油明胶微球栓塞Beagle犬肝动脉后的病理改变,为临床实验提供依据.方法 Beagle犬随机分为生理盐水组(10ml/kg)、空白微球组(15mg/kg)、莪术油微球低剂量组(7.5mg/kg)和莪术油微球高剂量组(15mg/kg),每4周经肝动脉给药1次,连续给药3次,停药后观察4周.观察肝病理组织学改变.结果明胶微球肝动脉栓塞可致肝组织不可逆性损伤,高剂量组广泛全小叶坏死,低剂量组灶性坏死,空白微球组改变类似高剂量组,生理盐水组未见肝组织损伤.结论莪术油微球重复经Beagle犬肝动脉给药,可因肝动脉栓塞造成肝脏不可逆性缺血坏死.     

经导管动脉栓塞术治疗肝癌：最新临床证据

对不能接受根治性治疗如肝移植、肿瘤切除术或经皮射频消融术(radiofrequency ablation, RFA)的肝细胞肝癌(hepatocellular carcinoma,HCC)患者,经导管动脉化疗栓塞术(transarterial chemoembolization,TACE)或放疗栓塞术(transarterial radioembolization,TARE)是治疗的核心手段。近期研究证据显示：对于无血管侵犯、3 cm及以下单结节型HCC患者,TACE与肿瘤切除术及RFA后的5年总生存率相似。尽管已应用数十年,碘油(超液化碘油?,Lipiodol? Ultra Fluid, Guerbet,France)作为一种亲肿瘤性且不透射线的药物运输载体在肿瘤介入治疗中的地位依然重要。药物缓释微球(drug-eluting bead,DEB)是栓塞术中一种较新型的药物输送方式,既可维持药物浓度,也可持续释放抗癌药。现有三种DEB可供临床选择使用,即Tandem?(CeloNova Biosciences Inc.),DC-Beads?(BTG,UK)和HepaSphere?(BioSphere Medical,Inc.,USA)。经动脉TARE已被证实可安全有效地运用于晚期肝癌及有肝血管侵犯的患者。两种放射性栓塞微粒可供临床选择使用,即SIR-Spheres?(Sirtex Medical Limited,Australia)和TheraSphere?(BTG,UK)。本文总结肝癌经导管动脉治疗的关键临床试验。     

应用三丙烯微球行子宫动脉栓塞对子宫内膜微血管密度的影响

探讨应用三丙烯微球行子宫动脉栓塞术(UAE)对子宫内膜微血管密度(MVD)的影响。方法 69只健康雌性豚鼠按随机数字法分为对照组(n=12)、UAE组(n=45)及假手术组(n=12);UAE组内再随机分为A1、A2及A3 3个亚组(每组n=15)。UAE组动物应用三丙烯微球行双侧UAE术,术后A1及A2组各死亡1只,最终各入组14只,其余动物生存状态正常。假手术组经子宫动脉注入生理盐水。对照组不做任何处理。各组动物均于排卵期获取子宫标本:A1、A2及A3组动物分别于UAE术后7～15d、16～30 d及31 ～45 d内获取子宫标本;假手术组、对照组于术后16～30 d内获取子宫标本。应用免疫组化法检测各组子宫标本内膜基底层的微血管,计算MVD并进行对比分析。结果 A1、A2组MVD均低于对照组、假手术组[(9.64±2.48)条/视野、(14.36±2.73)条/视野比(18.44±3.20)条/视野、(17.63±2.71)条/视野,均P＜0.05];A2组的MVD高于A1组,而A3组的MVD(17.15±2.87)条/视野亦高于A2组(均P＜0.05)。对照组与假手术组、A3组的MVD之间差异并无统计学意义。结论 UAE术后子宫内膜的MVD在一定时期内有所下降,这可能对内膜容受性造成一定程度的负面影响。但随着栓塞后时间延长,MVD数量有逐渐恢复的趋势。     

32磷-玻璃微球经肝动脉综合性栓塞治疗晚期肝癌的副反应及其防治

观察磷球微球治疗晚期肝癌的副反应并探讨其防治方法。方法：１９９４年３月至１９９８年２月，采用＾３２磷－玻璃微球（ｐｈｏｓｐｈｏｒｕｓ－３２ｇｌａｓｓ ｍｉｃｒｏｐｈｅｒｅｓ，＾３２Ｐ－ＧＭＳ）２．６－１７．９ｍＣｉ，术中栓塞法附加肝动脉结扎及置管化疗２３例（ＯＡＥ＋ＨＡＬ），经Ｓｅｌｄｉｎｇｅｒ导管栓塞法２１例（ＴＡＥ），以纯甘油或碘化油作媒介加化疗药制成放化疗综合性栓塞液，结果：全组ＯＡＥ＋ＨＡ     

三丙烯微球栓塞子宫动脉对子宫内膜血管的影响

背景：子宫动脉栓塞已广泛应用于临床治疗多种妇产科疾病,但对于子宫动脉栓塞后子宫内膜微血管密度的有何变化及新生血管的形成至今少有文献报道。 目的：观察子宫动脉栓塞对子宫内膜微血管密度及新生血管形成的影响。 方法：60只雌性豚鼠随机分为对照组(n=15)及子宫动脉栓塞组(n=45),子宫动脉栓塞组动物应用三丙烯微球行双侧子宫动脉栓塞。子宫动脉栓塞组再随机分为E1,E2及E3三个亚组(n=15),分别于子宫动脉栓塞后7-15 d,16-30 d及31-45 d内获取子宫标本。 结果与结论：常规病理染色显示豚鼠子宫动脉一级分支、浆膜下动脉支及子宫肌层微小动脉血管内均可见大小不等栓塞微球分布。子宫动脉栓塞豚鼠子宫内膜基底层微血管密度CD34在子宫动脉栓塞后降低,而后随时间的延长而增加(P < 0.05);而子宫动脉栓塞豚鼠子宫内膜基底层微血管密度CD105在子宫动脉栓塞后增加,而后随时间的延长而降低(P < 0.05)。提示随着栓塞后时间推延,新生微血管数量显著增加,基底层微血管密度有逐渐恢复趋势。     

免疫磁性海藻酸钠载药纳米微球的制备与评价

靶向治疗系统是目前研究的热点,用微乳化-离子交联方法制备包覆阿霉素的碳包铁/海藻酸钠复合纳米微球,以水溶性碳二亚胺为交联剂,将载药微球与单抗Hab18连接,制备出了免疫磁性药物纳米微球.对该免疫磁性微球的理化性能进行了表征,同时检测了免疫磁性微球中抗体的活性和免疫磁性微球与靶细胞的体外结合情况,结果表明,免疫磁性药物纳米微球平均粒径约为171.2nm,外观为球型,铁含量为14.6%,载药量为10.8%,且具有强磁响应性和长时间药物缓释效果.同时在体外该微球能够与靶细胞特异性结合.这种免疫磁性药物纳米微球有望成为一种优良的靶向肿瘤药物载体.     

海藻酸钠微球支气管动脉栓塞材料治疗肺结核大咯血的有效性

背景：临床对肺结核大咯血患者实施支气管动脉栓塞介入治疗过程中,可以选择不同的栓塞材料,其中海藻酸钠微球和明胶海绵是两种常用的材料,但目前关于两种材料应用效果的比较分析相关报道相对较少。目的：分析海藻酸钠微球支气管动脉栓塞治疗肺结核大咯血的临床有效性。方法：纳入157例肺结核大咯血患者,其中男98例,女59例,年龄22-75岁,均实施支气管动脉栓塞治疗,按照栓塞材料的不同分为海藻酸钠微球组(n=74)和明胶海绵组(n=83)。栓塞治疗后随访12个月,观察两组临床疗效、复发情况及并发症发生情况。结果与结论：经疗效判定,海藻酸钠微球组和明胶海绵组的治疗总有效率分别为91.2%和81.9%,组间治疗总有效率比较差异有显著性意义(P < 0.05); 海藻酸钠微球组和明胶海绵组的复发率分别为6.8%和26.5%,组间复发率比较差异有显著性意义(P < 0.05);两组并发症发生情况比较差异无显著性意义(P > 0.05)。表明海藻酸钠微球支气管动脉栓塞治疗肺结核大咯血临床有效率高、复发率低,效果更理想。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Pathological findings of uterine leiomyomas and adenomyosis following uterine artery embolization

Uterine artery embolization (UAE) is an effective and accepted treatment option for symptomatic uterine leiomyoma. Between 2000 and 2005, 91 women were treated using this method, and were prospectively followed at our institution. Twenty of them subsequently underwent surgery. One of these patients was subjected to four surgical procedures. We describe the pathological findings of 23 surgical specimens obtained from these 20 patients. The embolic material used consisted of tris-acryl gelatin microspheres (TGMS) in 15 patients (18 surgical specimens), polyvinyl alcohol particles (PVA) in three patients, and a combination of PVA and TGMS in two patients. Histologically, of the 23 specimens examined, 20 were diagnosed as leiomyomas, and three as adenomyosis. Particles used for embolization were found in all but three specimens. Necrosis was present in 15 of 20 leiomyoma specimens. Hyaline necrosis was found in 12 specimens, coagulative necrosis in one case, and a combination of hyaline and coagulative or suppurative necrosis in two cases. The foci of adenomyosis remained unaltered.     

Conservative treatment by angiographic uterine artery embolization of a 12 week cervical ectopic pregnancy

A 32 year old woman, gravid 1, nulliparous, was admitted to our department at 11 weeks and 2 days of gestation after being diagnosed with cervical pregnancy. She was unsuccessfully treated with methotrexate for 5 days. On the fifth day after admission she underwent bilateral uterine artery angiographic embolization followed by vacuum evacuation and curettage of the cervical canal. A Foley catheter was also inserted in the cervical canal and left in place for 4 days. The patient was discharged in good condition on the seventh postoperative day.     

子宫动脉栓塞术在子宫疤痕部位妊娠的应用

目的 探讨子宫动脉栓塞术在治疗子宫疤痕部位妊娠的应用价值.方法 回顾性分析16例剖宫产术后子宫疤痕部位妊娠患者的临床资料.有7例在行双侧子宫动脉栓塞术后4～5 d再行清宫术;9例直接行清宫术或剖腹探查术.给果 7例行双侧子宫动脉栓塞术患者手术均一次成功,术中术后出血少,恢复快;9例行清宫术或剖腹探查术,术中术后出血多,恢复慢.结论 子宫疤痕部位妊娠患者经子宫动脉栓塞术预处理后,手术的出血及风险可明显减少,成功率高.     

Diagnosis analysis in breast cancer and cervical cancer screening

Assessment of the accuracy of diagnostic procedures has been made independent of the diagnostic criteria used by means of Relative Operating Characteristics (ROC) analysis. A ROC curve describes the mutual relationship between the sensitivity and specificity of a diagnostic decision on the basis of various diagnostic criteria. The construction of such ROC curves is made possible if diagnoses are graded into levels of certainty. The curve enables the choice of an operating point with predetermined sensitivity and specificity values for the diagnosis decision. The population-based breast-cancer and cervical cancer screening projects carried out in Utrecht demonstrated an excellent fit between actual data and the calculated ROC curves. Analysis of the accuracy or performance of cytological diagnosis uncovered a problem arising from the similarly graded histopathological reference criteria used to determine the 'truth' of the cytological diagnosis decisions. The proposed solution is a serial calculation of ROC curves, one for each level differentiating between the histopathological categories. The ensuing three-dimensional ROC hill may reveal a summit marking numerically advantageous diagnosis criterion levels for both the test and the disease to be detected, or a depression signalling locally below-standard detection performance.     

Raf激酶抑制蛋白在宫颈癌中的表达及其临床意义

目的 探讨Raf激酶抑制蛋白(Raf kinase inhibitor protein,RKIP)在宫颈癌中的表达及其临床意义.方法 应用免疫组织化学方法检测RKIP在正常官颈组织、官颈上皮内瘤变组织、官颈癌及其转移淋巴结组织的表达,并在体外应用RT- PCR及Western印迹方法检测RKIP mRNA及蛋白在4种不同来源的宫颈癌细胞系中的表达情况,探讨其与官颈癌临床病理学特征的关系.结果 RKIP在宫颈癌转移淋巴结中的阳性表达率低于宫颈癌组织;RKIP在宫颈癌组织的表达低于正常宫颈组织及宫颈上皮内瘤变组织,差异有统计学意义(x2 =9.211,P＜0.05);而RKIP在正常官颈组织及官颈上皮内瘤变组织的表达差异无统计学意义(x2=0.805,P＞ 0.05);RKIP在宫颈癌组织中的表达与淋巴结转移有关(x2=10.341,P＜0.05),与肿瘤的病理类型、分化程度及临床分期无关(x2分别为0.190、4.101、1.402,P＞0.05).RT- PCR及Western印迹结果显示RKIP在高侵袭性宫颈癌细胞系Caski中的表达低于其他各组(x2=4.08,P＜0.05).结论 RKIP基因在宫颈上皮内瘤变向官颈癌转变中可能起重要作用,是官颈癌发生淋巴结转移的重要标记.     

Role of cervical screening in older women

Objective

To review the literature concerning the role of cervical screening in women 60 years and older.

Methods

Literature review was conducted using PubMed and the search terms cervical neoplasm, cancer, middle aged, elderly, aged, postmenopausal, cervical cytology and screening. To be included in the review, the article must have been in the English language. The search focused on publications from 2000 forward.

Results

The case control and modeling studies that addressed the role of cervical cytology screening in women 60 and older were reviewed. The outcomes of interest included: (1) the benefits of screening in terms of decrease rate of cervical cancer incidence (6 studies) and mortality (3 studies); (2) the duration of protection of the last screening test (4 studies); and (3) the harms of screening older women including false positive test results and cost.

Conclusions

Cervical cytology screening is beneficial for women over 60 years in terms of preventing the occurrence and death from cervical cancer. A negative cytology test appears to have 5 years of protection in this age group. Age of last screen with in an organized screening program may differ compared to the goals and wishes of individual women.