HepaSphere栓塞微球临床应用及病例分享.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,HepaSphere,栓塞微球临床应用及病例分享,1990:,由日本教授,Hori,发明，名称：,SAP,*,1992:,首次应用于临床,2000:,应用于,HCC,的初步研究,2004:,获得欧盟认证，名称：,HepaSphere,2006:,获得美国认证，名称：,QuadraSphere,历史,*,SAP,：,Superabsorbent Polymer Microsphere,HepaSphere,的,材质,乙酸乙烯,和,丙烯酸甲酯,经聚合皂化反应生成的共聚物,聚丙烯酸钠乙烯醇,(poly vinylalcohol-co-acrylic acid),可压缩直径的,80%,良好的弹性，撤掉外力即可恢复原来的形状,可变形，能复原,像棉花糖一样,HepaSphere,的物理性能,TACE,精,准的靶向性（,T,argeted,）,良好,的吸收性（,A,bsorbing,）,高度,的随形性（,C,onforming,）,真正,的载药性（,E,luting,）,HepaSphere,的特性,HepaSphere,微球粒径分布均一,50-100um,粒径,HepaSphere,微球，,95%,在,40-110um,区间内,粒径均匀，更易完成指定层面栓塞,Guido Poggi et al.Transhepatic arterial chemoembolization with oxaliplatin-eluting microspheres(OEM-TACE)for unresectable hepatic tumors,Anticancer Res.2008 Nov-Dec;28(6B):3835-42,精准的靶向性（,T,argeted,）,HepaSphere,不会在血管近端或者远端发生,聚集,在,体内栓塞的血管直径与其粒径大小,一致,Khankan AA,Osuga,K,Hori S et,al.Embolic,effects of superabsorbent polymer microspheres in rabbit renal model:comparison with,tris,-acryl gelatin microspheres and polyvinyl alcohol.,Radiat,Med 22:384390,Bilbao,Jl,De Luis E,Garcia De,Jalon,JA et al.Comparative study of four different spherical embolic particles in an animal model:a morphologic and histologic evaluation.J,Vasc,Interv,Radiol,.2008 Nov;19(11):1625-38,精准的靶向性（,T,argeted,）,良好的吸收性（,A,bsorbing,）,Hepa,膨胀的大小受控于水基溶液的离子浓度,在人体组织上得到的证实：与血管内皮紧密接触并随形，从而达到完全性栓塞的效果,Klass et al 2014.ANTICANCER RESEARCH 34:3597-3606(2014),高度的随形性（,C,onforming,）,机械吸收,HepaSphere,由干燥的颗粒变成水合微球,约在,10,分钟内完成,正负电荷结合,HepaSphere,微球带负电荷的丙烯酸酯与带正电荷的盐酸多柔比星之间形成离子键,1,Kos S et al.,Elution characteristics of doxorubicin-loaded microspheres differ by drug-loading method and microsphere size,J Vasc Interv Radiol.2011 Mar;22(3):361-8,真正的载药性（,E,luting,）,HepaSphere,为整体载药,1,，,2,Sebastian Kos et al.Elution Characteristics of Doxorubicin-loaded Microspheres Differ by Drug-loading Method and Microsphere Size,J vasc Interv radiol 2011;22:361-368,David M.Liu et al.Optimization of Doxorubicin Loading for Superabsorbent Polymer Microspheres:in vitro Analysis,Cardiovasc Intervent Radiol(2012)35:391-398,真正的载药性（,E,luting,）,HepaSphere,可,加载多种,药物：,多柔比星,1,顺,铂,2,3,4,伊立替康,5,奥沙利铂,6,Kos S et al.Elution characteristics of doxorubicin-loaded microspheres differ by drug-loading method and microsphere size,J,Vasc,Interv,Radiol,.2011 Mar;22(3):361-8,Maeda N et al.,In vivo evaluation of cisplatin-loaded superabsorbent polymer microspheres for use in chemoembolization of VX2 liver tumors,J,Vasc,Interv,Radiol,.2012 Mar;23:397-404,Maeda N et al.,In vitro characterization of cisplatin-loaded superabsorbent polymer microspheres designed for chemoembolization,J,Vasc,Interv,Radiol,.2010;21(6):87781,Huppert P,Transcatheter,Arterial Chemoembolization (TACE)of Colorectal Cancer Liver Metastases by,Irinotecan,-Eluting Microspheres in a Salvage Patient Population,Cardiovasc,Intervent,Radiol,.2013 May;37(1):154-164,Poggi G,Transhepatic,arterial chemoembolization with,oxaliplatin,-eluting microspheres(OEM-TACE)for,unresectable,hepatic tumors,Anticancer Res.2008 Nov-Dec;28(6B):3835-42,Poggi G,Oxaliplatin,-eluting microspheres for the treatment of intrahepatic,cholangiocarcinoma,:a case report,Anticancer Res.2008 Sep-Oct;28(5B):2987-90,真正的载药性（,E,luting,）,HepaSphere,的载药时间,Merit brochure,50-100,m HepaSphere:15,分钟加载,95%,以上,的多,柔比,星,按照麦瑞通推荐的载药方法可以,达到,这种,载,药效,果,Kos S et al.Elution characteristics of doxorubicin-loaded microspheres differ by drug-loading method and microsphere size,J Vasc Interv Radiol.2011 Mar;22(3):361-8,HepaSphere,的载药时间,术后第,1,天,术后第,3,天,术后第,7,天,术后第,14,天,将加载多柔比星的,HepaSphere,注入兔,VX2,肝肿瘤模型中，荧光成像证明术后,1,、,3,、,7,、,14,天均可探测到多柔比星渗透到周围组织中（多柔比星呈红色荧光）。,Gupta et al.“Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model.”,Cardiovasc Intervent Radiol,2011;34(5):1021-30.,HepaSphere,的,药代动力学特性,HepaSphere,能够,有效加载多柔比星,HepaSphere,做到,了持续释放，在各时间点均可提高肿瘤内多柔比星的,浓度,Lee et al.“Doxorubicin-Loaded QuadraSphere Microspheres:Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer.”,Cardiovasc Intervent Radiol,2010;33(3):57682.,HepaSphere,的,药代动力学特性,Hepa,提高了肿瘤局部的药物浓度,Grosso et al.“Transarterial Chemoembolization for Hepatocellular Carcinoma with Drug-Eluting Microspheres:Preliminary Results from an Italian Multicentre Study.”,Cardiovasc Intervent Radiol,2008;31:1141-49.,OR,在,1,个,月,和,6,个,月,时分别为,84%,和,77.4%,9,个月的生存率为,92%,HepaSphere,的肿瘤反应率,Seki et al 2011.Cardiovasc Intervent Radiol(2011)34:557565,病灶平均直径为,6.4cm,（,4-12cm,），,证实针对,大肝癌,，,HepaSphere,也是有效的,HepaSphere,的肿瘤反应率,p 0.0001,P=0.007,Malagari et al 2014.Cardiovasc Intervent Radiol(2014)37:165175,HepaSphere,显著降低,AFP,水平,Italy,Greece,Malagari et al 2014.Cardiovasc Intervent Radiol(2014)37:165175,Dekervel et al 2014.J Vasc Interv Radiol 2014 Feb;25(2):248-55,Seki et al 2011.Cardiovasc Intervent Radiol(2011)34:557565,77%,73.7%,100%,HepaSphere,能延长生存期,HepaSphere,的肿瘤反应率及生存期,Malagari K.et al.Chemoembolization of hepatocellular carcinoma with HepaSphere.Hepatic Oncology,Vol.2,No.2,Pages 147-157(2015).,CR,：,22.2-48%,，,PR,：,43.7%-51%,1,年生存率,：,73.7-100%,van Malenstein H et al.“A Randomized Phase II Study of Drug-Eluting Beads versus Transarterial Chemoembolization for Unresectable Hapetocellular Carcinoma.”,Onkologie,2011;34:368-76.,肝功能保护好，安全,可靠,Hepa,组的肝功能变化平稳，基本与术前无,变化,cTACE,组肝功能,变化很大,，术,后,一个月才,降低到术前,水平,HepaSphere,的安全性,Malagari et al 2014.Cardiovasc Intervent Radiol(2014)37:165175,HepaSphere的安全性,Van Malenstein et al.ILCA 2009,HepaSphere,的安全性,多项研究显示,Hepa,的,PES,发生率小于,20%,Malagari,et al 2014.,Cardiovasc,Intervent,Radiol,(2014)37:165175,Grosso,et al 2008.,Cardiovasc,Intervent,Radiol,.2008 Nov-Dec;31(6):1141-9,Seki,et al 2011.,Cardiovasc,Intervent,Radiol,(2011),34:557565,HepaSphere,的安全性,HepaSphere,临床应用病例,黄,xx,主诉：,上腹部闷胀,1,月,当地全腹部,CT,：,1.,考虑胰腺炎，考虑少量积液；,2.,左肾上极占位，考虑肾癌与错构瘤鉴别。,2015-09-24,我院行,PETCT,提示：,1.,左肾上极占位性病变，病灶局部糖代谢未见异常（等代谢病变），结合,CT,动态增强密度改变，考虑左肾透明细胞癌（低级别）。,2.,左肺上叶磨玻璃阴影，病灶糖代谢稍增高，考虑早期肺浸润性腺癌与炎性病变鉴别，前者可能性较大。,2015-09-24,我院,PETCT,：,左肾上极见一类圆形肿块影，大小约为,2.82.6cm,，边界清楚。,三期增强扫描示病变皮质期明显强化，强化程度接近皮质强化程度，实质期及延迟期病变强化程度减低，局部,FDG,药物摄取未见明显增高。,延迟,2,小时扫描可见,FDG,药物摄取未见增高，病灶,FDG,摄取分布与肾组织影分界不清。,2015-9-30,行经皮肾动脉栓塞术，,DSA,示：左肾上级病灶，实质期可见肿瘤染色。使用微导管进入肿瘤动脉，配置,THP,载药微球，经微导管注入载药微球共,5ml,，后造影示肿瘤供血动脉血流较前明显减慢，再经微导管注入,300-500um,栓塞微球。,术后,1,月返院复查,2015/11/06,腹部,CT,：双肾及双肾上腺,:,形态、大小未见明显异常；左肾上极见类圆形低密度灶，边界清晰，增强扫描呈明显不均匀性强化病灶向肾轮廓外突起；大小约,21mm18mm,；双侧肾盂、肾盏未见明显扩张积水。,术后,1,月返院复查,2015/11/06,腹部,CT,：,双肾及双肾上腺,:,形态、大小未见明显异常；左肾上极见类圆形低密度灶，边界清晰，增强扫描呈明显不均匀性强化；病灶向肾轮廓外突起；大小约,21mm,18mm,；双侧肾盂、肾盏未见明显扩张积水。,彭,xx,主诉：,体检发现肝内占位,1,月,当地全腹部,CT,：,马来西亚当地医院行上腹增强,MRI,提示肝恶性肿瘤（具体报告未见）,查,AFP,：,904ug/L,。,2015-08-06,于我院行全身,PET/CT,检查示：,肝,S8,、,4,可见一巨大软组织肿块影，大小为,9.9*9.5cm,，边界尚清，肝,S8,、,4,肿块及肝多发结节代谢不同程度增高，考虑肝癌并肝内多发子灶形成。,2015-08-06,于我院行全身,PET/CT,检查示：,肝,S8,、,4,可见一巨大软组织肿块影，大小为,9.9,9.5 cm,，边界尚清，平扫为低密度，密度不均匀，内见多发斑片状低密度区，增强扫描动脉期呈全瘤范围不均匀强化，高于正常肝实质密度，但低于同层主动脉密度。,门脉期及静脉期肿块强化迅速降低，明显低于正常肝实质。三期增强扫描符合,“,快进快出,”,强化模式。肿块,FDG,摄取浓聚增高。肝,S4,及,S6,可见数个类似强化结节影，较大约,2.7,2.4cm局部,FDG,摄取增高。,2015-08-06,于我院行全身,PET/CT,检查示：,肝,S8,、,4,可见一巨大软组织肿块影，大小为,9.9,9.5 cm,，边界尚清，平扫为低密度，密度不均匀，内见多发斑片状低密度区，增强扫描动脉期呈全瘤范围不均匀强化，高于正常肝实质密度，但低于同层主动脉密度。,门脉期及静脉期肿块强化迅速降低，明显低于正常肝实质。三期增强扫描符合,“,快进快出,”,强化模式。肿块,FDG,摄取浓聚增高。肝,S4,及,S6,可见数个类似强化结节影，较大约,2.7,2.4cm,，局部,FDG,摄取增高。,2015-09-01行经皮肝动脉栓塞术，用微导管超选入肝右动脉肿瘤供血动脉，将碘化油10ml+造影剂10ml+洛铂50mg配置为碘化油乳剂，经微导管注入碘化油乳剂约5ml。后于右肝肿瘤末支注入栓塞载药微球（吡柔比星50mg），至血流明显缓慢为止。术后于肝右动脉造影，血流较前明显减缓，可见碘油沉积。,2015-10-20行经皮肝动脉栓塞术。造影示：肠系膜上动脉未有分支参与肝脏供血，腹腔干发出脾动脉、胃左动脉及胃十二指肠动脉，肝右动脉略增粗迂曲，动脉期右肝肝S8、S4见类圆形大小约72mm57mm肿瘤染色影，超选入肝右动脉肿瘤供血动脉，考虑有分支动静脉瘘，注入混悬液明胶海绵。后于右肝肿瘤末支注入栓塞载药微球（THP 50mg），至血流明显缓慢为止。,2015-11-13行经皮肝动脉栓塞术。造影示：肠系膜上动脉未有分支参与肝脏供血，腹腔干发出脾动脉、胃左动脉及胃十二指肠动脉，肝右动脉略增粗迂曲，动脉期右肝肝S8、S4段见多发肿瘤染色影。后于右肝肿瘤末支注入栓塞载药微球（THP 50mg）+100-300um栓塞微球一支，至血流明显缓慢为止。,返院复查,2015,年,12,月,15,日,AFP(,发光法,)552.95ng/ml,2015/12/15,腹部,CT,：肝,S8,、,4,见类圆形大小约,97mm51mm,异常密度影，肝动脉内见结节样高密度影，病灶内见少量点片状碘油沉积区及积气，病灶边界欠清；三期增强扫描病灶周边及内部仍可见小片状异常强化影，呈“快进快出”强化特征，动脉期病灶可见明显不均匀强化，门静脉期及平衡期强化减弱；病灶周边见多发大小不等类圆形低密度影，强化方式与上述病灶相同。门静脉及分支未见异常。与,2015-11-11CT,对比，肝内碘油沉积较前大致相同，病灶范围及异常强化较前缩小，病灶内坏死增多。,2015/10/19 2015/12/15,Thank you,