Name: percutaneous hepatic perfusion (php) with melphalan as a treatment for unresectable metastases confined to the liver
Uploaded: 2016-07-31T14:00:00.000+00:00
Duration: 9 min 2 s
Description: Watch this Scientific Journal Video about Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver at JoVE.com

The authors have no acknowledgements. 
The phase II study is financially supported by Delcath Systems.

注意:在病人符合所有纳入标准，由肿瘤内科，外科医生和麻醉师进行仔细评估，病人被列入研究。所有患者签署知情同意书。这两个临床研​​究是由荷兰莱顿大学医学中心的地方医学伦理委员会批准，并按照赫尔辛基宣言的道德标准执行。 1.预程序通过介入放射造影<ol><li>在对PHP程序编写，执行前的程序性血管造影到PHP动脉解剖映射20数天前。在此过程中执行的肠系膜动脉（SMA），腹腔干和肝动脉血管造影术。21 <ol><li>在血管造影术，用泵喷射到使用2.4F或2.7F微导管的肝动脉和肺叶动脉使用造影剂。 （ 材料列表中，7项）。 </li><li>注入在5毫升/秒的从肝总动脉的速率为血管造影的15ml未稀释的对比度（碘普罗胺300）（ 物料清单 ，第14项）和12ml在为大叶性肺炎注射3毫升/秒。21 </li><li>划定肝血管解剖和血管瘤供给通过如步骤1.1.2中描述注入对比度。21 </li><li>确定化疗剂的回流的风险hepatico肠吻合（如胃或胃右动脉）。21确定血管的变体，例如异常右侧或左侧肝动脉。21 </li><li>在回流的可能的风险的情况下，如果有合适的肝动脉远端胃十二指肠动脉（GDA）小于约1厘米，栓塞此动脉可拆卸微线圈或血管塞（ 物料清单 ，项目15和16）。还栓塞其它胃 - 和/或肠溶吻合，以防止chemothe的流raputic药物的其他结构。21 </li><li>栓塞动脉分支远端的血管供应，胃，胰腺和膈肌的肠道输注部位。21 </li></ol></li></ol> 2. PHP程序一:准备和创建灌注环路<ol><li>通过额外的肉体灌注师准备（ECP） <ol><li>收集chemosaturation tubingpack，chemofilters和离心泵。 （ 物料清单 ，物品1b和12），这些项目被包装在由制造商提供的框。 </li><li>冲洗用CO 2气体完全体外循环回路。 </li><li>素与包括过滤器的NaCl 0.9％和肝素（2000 IU / L）的电路。 <ol><li>冲洗体外循环系统用6L肝素的0.9％NaCl的，​​最初由重力作用的手段作为超准已经存在于系统中。碳过滤器完全水化后，用离心pUMP施加更大的压力上的过滤器，以除去剩余的气泡。 注:有点锤可用于通过振动和共振以除去气泡。 <ol><li>总理双球囊导管线和旁通管线。 </li><li>素左chemofilter（1升）和去泡，然后素权利chemofilter（1升）和去泡。 </li><li>系统初始启动后慢慢水合物chemofilters（每盒3升）。这可能需要每chemofilter 10-20分钟。 </li><li>贷泡沫陷阱（动脉过滤器）。 </li></ol></li></ol></li><li>检查和校准流量传感器和压力监视器，如在离心泵软件菜单编程，根据制造商的说明。 </li></ol></li><li>血管造影室由麻醉师病人准备<ol><li>成立了麻醉管理所需的监控: <ol><li>放置一个血压频带用于非侵入性的血压测量心电图对病人的心电监护胸部以及血氧饱和监护电极。 </li></ol></li><li>放置在患者的前额一个双频指数量表（BIS）的传感器来测量麻醉的病人的深度，在这种情况下，麻醉师被用来与此工作。 </li><li>根据制造商的说明，包括通过通气机和气管内导管的ET-CO 2设置通风设备。放置在其中的IR站立的患者的相反侧的通气机的指示，由制造商。 </li><li>放置在血管造影室的桌子病人，直接盖上温暖的空气毯子十个分量常温病人。 </li><li>发生在右臂静脉第四麻醉药和静脉输液给药外周静脉通路。 </li><li>诱导麻醉（与麻醉师的偏好麻醉剂），进行气管插管，并开始INTermittent正压通气（IPPV）。 </li><li>维持麻醉到BIS = 50，MAP = 65毫米汞柱，0.5毫升/ kg / hr的normuria。 </li><li>将鼻咽体温温度计。 </li><li>地方对神经肌肉阻滞监测四（TOF）电极列车在制造商的说明（在麻醉师的偏好）。 </li><li>设置并准备作为制造商的说明快速的流体管理系统/或液体加热器（ 物料清单 ，第2项）。 </li><li>打开先进的显示器屏幕（ 物料清单 ，项目4）上，并连接所有电缆。 </li><li>插入一个22克动脉线成平均动脉压（MAP）监测左桡动脉。 （ 材料清单 ，第3项）。 </li><li>放置在左内颈静脉中心静脉压测量中心静脉线。 </li><li>插入膀胱导管。 </li><li>保持常温bŸ暖空气的毯子和温暖的静脉输液。 </li><li>使用整个程序的高级监视器（ 物料清单 ，项目4）显示器CVP和动脉血压。 </li><li>通过绘制一个血液样品和将其放置在对ACT计确定基线活化凝血时间（ACT）。 </li><li>此外，在感应静脉给予头孢唑啉1克，泮托拉唑40毫克的氢化可的松300毫克。 </li></ol></li><li>药剂师准备<ol><li>重组美法仑（3.0毫克/千克体重（最大剂量220毫克）（ 物料清单 ，第9项））通过使用无菌针10毫升供给稀释剂的迅速直接注入冻干粉末的小瓶（20克或更大的针直径）和注射器。 </li><li>直到得到明确的解决方案，立即摇瓶剧烈。这提供了美法仑的5毫克/毫升的溶液。 </li><li>立即稀释剂量以在NaCl 0.9％注射，USP，在浓度不大于0.45毫克/毫升更高。 </li><li>重建的60分钟内完成管理工作。 </li></ol></li><li>准备在血管造影室由介入放射（IR） <ol><li>在一张桌子布置了必要的工具和用品（无菌）。 （ 材料清单 ，物品1A，3,5,6,7,8,11）。 </li><li>盖上无菌床单病人。 </li></ol></li><li>通过IR护套的位置<ol><li>使用超声引导为笔杆的内部颈静脉（IJV）左，右的位置。 </li><li>放置一个7.5F三腔静脉留置针，在左侧颈内静脉20厘米（ 物料清单 ，项目5）。此鞘是由麻醉师为CVP测量和拟交感神经药输注使用。 </li><li>放置在右颈内静脉一10F静脉回流导管（ 物料清单 ，项目1A）。此护套被用于过滤的血液的体外chemofiltratio后静脉回流ñ。 </li><li>放置5F鞘进入左股总动脉（CFA）（ 物料清单 ，项目6）。 注意:此鞘用于同轴放置微导管注入化疗剂。 </li><li>放置一个18F护套与8-10F和12-14F扩张器串行散瞳后右股总静脉（CFV）（ 物料清单 ，项目8）。使用扩张器来调整插入口大小合适，最终正确放置18F护套。注:此套用于引入双球囊导管（隔离抽吸导管）。 </li></ol></li><li>肝静脉的分离和主体外创建电路<ol><li>辖肝素鞘全部已放置后;在300 IU /公斤（ 物料清单 ，项目11）的初始剂量。 </li><li>保持高于50秒的活化凝血时间（ACT）用另外的肝素推注剂量在整个过程中根据需要。 </li><li>站RT去甲肾上腺素（50毫升为0.2mg / ml）的0.1-2微克/公斤/分钟和去氧肾上腺素（50毫升0.1毫克/毫升）0.1-2微克/千克/分钟，输液（500毫升晶体液），以保持密切的血流动力学参数至65毫米汞柱的平均动脉压（MAP），和0.5毫升/公斤/小时尿量。 </li><li>通过在左股总动脉的5F鞘，引入2.7F微导管（ 物料清单 ，项目7）同轴并放置在用血管造影术监测适当的肝动脉或肺叶动脉。 </li><li>通过在右股总静脉18F护套，引入16F双气囊导管（隔离抽吸导管）中，用在使用血管造影术监测右心房的尖端放置。 </li><li>导管的放置后直接，这些附加使用特殊的连接点体外循环系统;静脉回流线在IJV外皮和流出线路的隔离导管。 </li><li>开始的C如制造商所描述entrifugal泵: 注:所有线路现在是开放的，流动是运行在旁路管线。 </li><li>的0.5升的胶体溶液（ 物料清单 ，项目13）静脉输注后，膨胀用50％盐水 ​​和50％的造影剂混合物颅气球。 </li><li>与尾气球仍然瘪，慢慢缩回双气囊导管，直到颅气球是在右心房和下腔静脉（IVC）的连接点，就在肝右静脉上述（气球现在是楔形，如在图2中示出）。 </li><li>膨胀尾球囊用90％盐水和10％造影剂的混合物中，直到膨胀的气球的横向边缘开始成为由下腔静脉抹去。 注意:气球充气造影介质的不同混合物。尾气囊膨胀以阻塞肾静脉上方的下腔静脉，使肝静脉流出分离˚F<html> ROM全身静脉循环。最大的38毫升卷可能被注入到每一个气球。 </li><li>检查气球的定位和静脉造影排除泄漏<ol><li>通过注入加入20ml对比度进行静脉造影（ 即，碘普胺300）通过使用手注射双气囊静脉双气囊导管的开窗口。 </li></ol></li><li>如果对比度泄漏所看到的，重新定位气球或进一步膨胀气球和如在步骤2.6.11.1（ 见图2）中所述重复静脉造影。 </li></ol></li></ol><img alt="图2" src="/files/ftp_upload/53795/53795fig2.jpg" /> 图2.每程序血管造影。静脉双气囊导管在适当的肝动脉的下腔静脉和动脉灌注导管。逆行对比度经由静脉导管注入。从预程序血管造影和栓塞线圈到位。ww.jove.com/files/ftp_upload/53795/53795fig2large.jpg"目标="_空白"&gt;点击此处查看该图的放大版本。 <ol start="7"><li>闭合电路<ol><li>注入另一0.5L的胶体溶液中。确保这两个chemofilters是在这个时刻关闭，而旁通是开放的。 </li><li>尝试完成足够流量（Q = 400-500毫升/分钟）与安全压力近端（通常&lt;-70毫米汞柱）和远端离心泵（ 物料清单 ，项目12）（&lt;100毫米汞柱）。 </li><li>滴定去甲肾上腺素0.1-2微克/千克/分钟和苯福林0.1-2微克/千克/分钟和流体施用到保持为160毫米汞柱的收缩压和0.5毫升/公斤/小时的尿量。 </li><li>当足够的流量和压力被达到，打开一个过滤器之一。 注意:血液通道虽然过滤器将hemofiltrate血液和去除大部分的化学治疗剂。血液滤过发生在整个procedu重以及在"洗脱"期间直接以下化疗输注期间。在此洗脱期，即从肝组织返回化疗剂，从循环"洗出"。 </li><li>在140-160毫米汞柱之间的收缩压已经达到，关闭旁通管线。 注意:麻醉师应该准备遇到血压下降从预压的降低导致由于腔静脉闭塞，从血液穿过由chemofilters和chemofilters去除血管活性剂（ 例如，去甲肾上腺素和肾上腺素）的周围血管扩张可能内源NO产生的血管舒张作用。调整去甲肾上腺素和肾上腺素的输注速率相应保持65毫米汞柱的地图。 </li><li>通过执行造影（如在步骤2.6.11.1描述）检查双气囊导管的定位。 </li><li>通过注射进行反政府的血管造影T（碘普罗胺300）通过肝动脉微导管排除动脉痉挛。如果痉挛看出，辖硝化甘油100-200微克到肝动脉（如在步骤1.1和子步骤也描述）。 </li></ol> </li></ol> 3. PHP程序II:化疗间歇期的输液<ol><li>美法仑的输液 注意:输送系统电路的放置，美法仑的输注到肝动脉是通过微导管启动之后。 <ol><li>当建立一个稳定的流率，无泄漏存在，并且患者的血压是稳定的，剂量为3毫克/公斤到适当的肝动脉或依次到两个肺叶动脉注入美法仑。 <ol><li>不要开始化疗输液，直到MAP高于65毫米汞柱。 </li></ol></li><li>注入剂量的使用自动注射器将100ml药物在0.4毫升/秒的速率，约30分钟，unti微升完整剂量注射。 </li><li>输液过程中，每隔一段时间，执行动脉造影监测血管痉挛的发生和位置，并检查双气囊导管的通货膨胀对比度潮红。 （请参阅有关的造影剂信息的步骤2.6.11.1（静脉造影）和1.1和2.7.9（血管造影））。 </li><li>在血管痉挛的情况下，管理硝化甘油（100-200微克）。 </li><li>化疗药物输液30分钟后，继续血液滤过额外30分钟的清除期（见注步骤2.7.5）。 </li><li>辖术后疼痛控制10毫克静脉吗啡。 </li><li>在洗脱期后慢慢放气在腔静脉的两个气球。 </li></ol> </li><li>在输液的端部和导管的去除<ol><li>在清除期的结束时，清空体外循环回路尽可能然后停止体外灌注。 </li><li>停止centrifu加仑泵并断开管。 </li><li>取出双气囊导管和输液微，但保留访问鞘到位，直至凝固的标准化。血管闭合装置可被放置在共同的股动脉来实现止血。 </li><li>保持正确的颈内静脉回导管到位，直至凝血功能进行了标准化。 </li><li>保持7.5F在左侧颈内静脉三腔静脉留置针的地方本可以在麻醉后监护室（PACU）一起使用。 </li></ol> </li><li>麻醉和肝素化的结束 注意:在该过程的结束执行下列步骤，当自动输血结束。 <ol><li>关闭并删除旁路电路。 </li><li>停止去甲肾上腺素和肾上腺素的输液双气囊放气后立即生效。这是可能的，因为足够预紧返回到右侧心脏和chemofiltration的终止。 </l我&gt; <li>正常化与鱼精蛋白（1:1）凝固，新鲜冰冻血浆和/或冷沉淀物有或无血小板输血。检查之后ACT。 </li><li>血流动力学稳定和去甲肾上腺素和肾上腺素输注结束后，终止麻醉剂维持用药。 </li><li>病人已​​返回到自主呼吸和意识后，拔管患者的气管。 </li><li>病人转移到恢复室进行的重要功能（血压和凝血参数）监测的24小时。 </li><li>取出血管鞘，一旦血小板计数&gt; 50×10 9 / L，APTT &lt;1.5×正常，INR &lt;1.5。应用手工压迫达到止血和超过两个腹股沟施加压力绷带。 </li></ol> </li><li>术后护理<ol><li>监测患者在麻醉恢复室进行手术后的第一个24小时。 </li><li>检查导管inserti止血网站上与显示器脉搏，血压，温度，通风，体液平衡和疼痛分数以及凝结。 </li><li>病人转移到病房，术后1-2天。 </li><li>术后第2天的3放电病人，最后血液学和血液化学试验后。检查肝，创造毒性后续的基准-正常范围内的正常上限2秒内凝血酶原时间（PT），活化部分凝血活酶时间（APTT），血小板&gt; 75000 / 立方毫米无血小板输注或&gt; 100,000 /毫米3与输血，血红蛋白&gt; 10克/分升（&gt; 6.2毫摩尔/ L）和天冬氨酸转氨酶和丙氨酸氨基转移酶（AST / ALT）基准水平的10％以内返回。 </li><li>辖细胞集落刺激生长因子的支持（pegfilgastrim，0.6毫升一次性注射器），出院后或PHP处理后48小时之内。 </li></ol> </li></ol>

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J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemosaturation+with+percutaneous+hepatic+perfusions+of+melphalan+for+hepatic+metastases:+experience+from+two+European+centers.">Chemosaturation with percutaneous hepatic perfusions of melphalan for hepatic metastases: experience from two European centers.</a> Rofo. 186 (10), 937-944 (2014).</li><li>Pingpank, J. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+phase+III+random+assignment+trial+comparing+percutaneous+hepatic+perfusion+with+melphalan+(PHP-mel)+to+standard+of+care+for+patients+with+hepatic+metastases+from+metastatic+ocular+or+cutaneous+melanoma.">A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma.</a> J Clin Oncol. 28, 18s (2010).</li><li>Rothbarth, J., Vahrmeijer, A. L., Mulder, G. 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The authors have nothing to disclose.

<html>不可切除肝转移患者可全身疗法进行治疗。然而，对于患者的转移性葡萄膜黑色素瘤，没有标准的全身性治疗是可用的和免疫或靶向治疗尚未能够显示出改进的生存。分离出的肝灌注已经被证明是一种有效的治疗患者局限于肝脏不能切除的葡萄膜黑色素瘤转移。9,28对于大肠癌转移多种治疗系统性可供选择，但一些患者这些方案下进展或不能耐受这种处理因为毒性。 2009年，范Iersel和?...

恶性肝肿瘤切除术是治疗原发性和继发肝脏恶性肿瘤的首选。然而，患者大部分是不是因为扩展性疾病或转移灶的位置的候选人进行手术。对于患有大肠癌转移无法切除，全身治疗往往是首选的治疗方法。从葡萄膜黑色素瘤肝转移通常很小，而整个肝脏弥漫性扩散。没有标准的全身治疗可用于本组患者。局部治疗可以是全身性治疗的替代方案中，在的情况下转移局限于肝脏。 因为肝脏的特定血管解剖的，这个机构可以从体循环中分离出来。这使得高剂量化疗（IHP，隔离肝脏灌注）肝脏灌注。此外，肝脏恶性肿瘤具有从hepati主导或独占血管供应Ç动脉，所述非肿瘤性肝实质的供给而70-80％是来自门静脉的。1,2这种技术二十多年前开发的，治疗患者以从不同的主起源不可切除的转移。3， 4特别是眼色素层黑素瘤患者在肝转移可以是候选人IHP因为转移通常很小，而在整个肝传播，并且目前没有标准全身治疗是可用的。5,6 IHP的原理是从全身循环暂时隔离肝脏和用高剂量化疗灌注器官，导致高的局部药物暴露与全身性副作用的限制。7这种高化疗剂量将是有毒的和导致并发症当全身施用。大多数国际水文计划的研究，用马法兰进行，调查了治疗肝metastasi的。期从大肠癌患者，以及患者的葡萄膜黑色素瘤转移的开放性手术过程中IHP 8,9一些研究表明，这种疗法可能是有效的:用于治疗50-59％的肿瘤缓解率（部分和完全反应）肠癌和治疗转移性葡萄膜黑色素瘤68％的肿瘤反应率的报道。8,10,11,12尽管有这些治疗的结果，该过程从未被广泛接受，因为该过程的复杂性，医院的持续时间留和相关的发病率和死亡率。 经皮肝灌注（PHP）的提供内容微创替代IHP和使用阿霉素13和人体试验的第一个被Ravikumar 等人进行的在猪模型首次证明1993。在1994年14由于缺乏有效性的证据，该技术主要被摒弃了，直到2000年初，当它W¯¯在美国国家癌症研究所（NCI）在美国15 PHP期间作为重新评估，将导管经由股动脉置于经皮到适当的肝动脉注入化疗剂。第二导管经由股静脉置于下腔静脉抽吸肝chemosaturated流出（参见图1中的PHP的电路）。隔离抽吸导管放置在腔静脉是双气囊导管，禁止泄漏进入体循环。的吸气chemosaturated血液由双木炭过滤器过滤，并通过放置在颈内静脉的第三导管返回到患者。病人在逗留〜3天的长度医院收治。 PHP的过程在全身麻醉下的血管造影室通过由专用的介入放射学家，麻醉师的一个训练有素多学科小组和体外perfusio执行NIST。一个肿瘤外科和肿瘤科医生也是这个多学科小组的成员，特别是集中在告知病人，病人的选择和术后护理。 <img alt="图1" src="/files/ftp_upload/53795/53795fig1.jpg" /> 图1 PHP的电路的原理图的图像。该图显示的PHP电路的设置。它显示了超有形的旁通管路隔离的肝脏灌注电路。 <a href="https://www.jove.com/files/ftp_upload/53795/53795fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 这个最小侵入性手术用少手术并发症相关联，并且可以被重复多次（至少4倍）。此外，它只有大约需要3至4小时，病人恢复快。的PHP的优点是，转移的所有尺寸可以治疗，和微转移正在汤治疗d以及。另外，转移，贴近血管结构和胆管的位置，是不是为PHP的禁忌证。最初的研究用的第一代滤波器执行的，用77％（平均）滤波器提取效率。16最近，III期试验的结果由Hughes 等人发布。表示在葡萄膜肝无进展存活的显著改善黑色素瘤患者与PHP相比，最好的替代治疗护理肝转移。17 自2012年4月2 第二代滤镜。在临床前研究中的第二代滤波器提取美法仑的98％。一些研究和案例研究系列为PHP多种适应症已公布，但除了最近出版的三期临床试验，生存还没有广泛地进行了分析。16,18,19,20在本次调查中，我们重点介入RAdiology程序，以及麻醉管理和被在此过程中，以促进在其他医疗中心采用这种治疗方法中使用的额外的体外循环。

<table><tbody><tr><td>Delcath 2nd Generation Hepatic CHEMOSAT Delivery System&amp;nbsp;</td><td>Delcath Systems Inc., New York, New York, USA</td><td>602001 and 602002</td><td>Item no. 1</td></tr><tr><td>Isofuse Isolation Aspiration Catheter (Double Balloon Catheter)</td><td>Delcath Systems Inc., New York, New York, USA</td><td></td><td>Item no. 1a</td></tr><tr><td>10F Venous Return Catheter</td><td>Delcath Systems Inc., New York, New York, USA</td><td></td><td></td></tr><tr><td>Hemofiltration Cartridges</td><td>Delcath Systems Inc., New York, New York, USA</td><td></td><td>Item no. 1b</td></tr><tr><td>Circuit components</td><td>Delcath Systems Inc., New York, New York, USA</td><td></td><td></td></tr><tr><td>Level-1 rapid fluid management system</td><td>Smiths Medical</td><td></td><td>Item no. 2</td></tr><tr><td>22 G arterial line&amp;nbsp;</td><td>Arrow International Inc. /&amp;nbsp; Teleflex Inc.,Dublin, Ireland</td><td></td><td>Item no. 3</td></tr><tr><td>Vigileo, Monitor</td><td>Edwards Lifesciences Corp, Irvine, California, USA</td><td></td><td>Item no. 4</td></tr><tr><td>7.5F Triple lumen intravenous catheter, 20 cm&amp;nbsp;</td><td>Vygon, Valkenswaard, Nederland</td><td></td><td>Item no. 5</td></tr><tr><td>5F sheath&amp;nbsp;</td><td></td><td></td><td>Item no. 6</td></tr><tr><td>2.7 Progreat microcatheter&amp;nbsp;</td><td>Terumo, Tokyo, Japan</td><td>MC-PP27131</td><td>Item no. 7</td></tr><tr><td>18F sheath&amp;nbsp;</td><td></td><td></td><td>Item no. 8</td></tr><tr><td>Auto-injector Medrad Mark V ProVis</td><td>Bayer, Indianola, Pennsylvania, USA</td><td>Not available anymore, replaced by&amp;nbsp;Medrad&amp;nbsp;Mark 7 Arterion&amp;nbsp;Injection System</td><td>Item no. 9</td></tr><tr><td>Melphalan</td><td>Alkeran, Aspen Pharmacare, Dublin, Ireland</td><td></td><td>Item no. 10</td></tr><tr><td>Heparin LEO, 5,000 IE/ml</td><td>LEO Pharma AB, Denmark</td><td></td><td>Item no. 11</td></tr><tr><td>Centrifugal pump</td><td>Medtronic, Minneapolis, Minnesota, VS</td><td></td><td>Item no. 12</td></tr><tr><td>Voluven colloid solution (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection)</td><td></td><td>Item no. 13</td><td></td></tr><tr><td>Iopromide 300, Ultravist</td><td>Bayer, Indianola, Pennsylvania, USA</td><td></td><td>Item no. 14</td></tr><tr><td>Detachable coil, Interlock</td><td>Boston Scientific, Marlborough, Massachusetts, USA</td><td></td><td>Item no. 15</td></tr><tr><td>Vascular plug, Amplatzer 4</td><td>St. Jude Medical, St Paul,Minnesota, USA</td><td></td><td>Item no. 16</td></tr></tbody></table>

percutaneous hepatic perfusion (php) with melphalan as a treatment for unresectable metastases confined to the liver

结直肠癌的无法切除的肝转移可全身化疗进行治疗，旨在限制疾病，延长生存期或将无法切除的转移到可切除的。然而，一些患者患下全身治疗的副作用或进展。对于患者转移葡萄膜黑色素瘤没有规范的系统治疗方案。对于患者无肝外疾病，隔离肝脏灌注（IHP）可以使全身的副作用有限的地方疾病控制。以前，这是开放式手术过程中提供满意的结果进行，但发病率和死亡率有关的开放过程中，禁止一个广泛的应用。因此，经皮肝动脉灌注（PHP）并同时chemofiltration开发。除了降低的发病率和死亡率，此过程可以重复，希望导致更高的响应速率和改进的生存期（由疾病的局部控制）。在PHP，猫heters被放置在适当的肝动脉，注入化疗剂，并在下腔静脉以吸入chemosaturated血液通过肝静脉返回。的腔静脉导管是双气囊导管禁止泄漏进入全身循环。血液从肝静脉返回通过导管穿孔吸出，然后通过一个额外的有形过滤系统灌注。过滤后，将血液中的右颈内静脉返回到患者通过第三导管。 PHP期间美法仑的高剂量输注进入肝脏，其中是有毒的，当全身给药会导致危及生命的并发症。因为从腔静脉闭塞和chemofiltration，血液动力学监测和血流动力学支持体的组合得到的显著血流动力学不稳定的这一复杂过程中是非常重要的。

知识关于PHP是基于我小的相位和II期试验和案例系列和最近的大阶段III试验;公布的结果的概述示于表1中 。一个论述了麻醉过程，血流动力学和治疗的代谢方面的问题。然而，据报道没有生存的数据。所报告的22三个更大的试验，包括从不同的原发肿瘤转移肝脏疾病，因此，结果是难以解释。16,22第一手稿出版于1994年和5-FU和阿霉素是使用。...

Watch this Scientific Journal Video about Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver at JoVE.com

Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

在这个手稿中，我们描述了同时作为chemofiltration治疗不能切除的肝转移经皮隔离肝脏灌注。这个程序是在全身麻醉下在angiosuite由经验丰富的团队进行，包括介入放射学家，临床灌注师和麻醉师的。

经皮肝脏灌注（PHP）与美法仑作为囿于肝脏不能手术切除转移的治疗

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn ...

percutaneous-hepatic-perfusion-php-with-melphalan-as-treatment-for

Research

JoVE Journal

Medicine

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

11.8K 次观看.  Leiden University Medical Centre. 在这个手稿中，我们描述了同时作为chemofiltration治疗不能切除的肝转移经皮隔离肝脏灌注。这个程序是在全身麻醉下在angiosuite由经验丰富的团队进行，包括介入放射学家，临床灌注师和麻醉师的。 

视频: Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Transradial Access Chemoembolization for Hepatocellular Carcinoma Patients

Transarterial chemoembolization (TACE) is the most common modality for treatment of hepatocellular carcinoma (HCC) at the intermediate stage. TACE is typically performed via transfemoral access (TFA). However, transradial access (TRA) is preferred in coronary artery interventions due to decreased complications and mortality. Whether the advantages of TRA can be applied to TACE required investigation.
Patients receiving TRA TACE at a single center were retrospectively enrolled for study. Procedural details, technical success, radial artery occlusion (RAO) rate, and access site-related bleeding complications were evaluated. From October 2017 to October 2018, 112 patients underwent 160 TRA TACE procedures. The overall technical success rate was 95.0% (152/160). The rate of crossover from TRA to TFA was 1.9%. No access site-related bleeding complications were found in any cases. Asymptomatic RA occlusion occurred in three patients (2.7%). Compared with TFA, TRA can increase safety and patient satisfaction while decreasing access site-related bleeding complications. Moreover, TRA interventions can benefit patients with advanced age, obesity, or a high risk of bleeding complications.

Transarterial chemoembolization (TACE) is the standard therapy for patients in the intermediate stage of hepatocellular carcinoma and is typically performed through femoral artery access. Compared with transfemoral access, transradial access (TRA) can decrease the rate of bleeding complications and improve patient tolerance. A method is presented here to perform transarterial chemoembolization via radial artery access.

肝细胞癌患者的跨径向获取化疗

Transarterial chemoembolization (TACE) is the most common modality for treatment of hepatocellular carcinoma (HCC) at the intermediate stage. TACE is ...

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科研

癌症研究

Dual-phase Cone-beam Computed Tomography to See, Reach, and Treat Hepatocellular Carcinoma during Drug-eluting Beads Transarterial Chemo-embolization

The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 dimensional&#160;(3D) diagnostic imaging in the interventional suite and can enhance minimally-invasive therapy beyond the limitations of 2D angiography alone. The role of CBCT has been recognized in transarterial chemo-embolization (TACE) treatment of hepatocellular carcinoma (HCC). The recent introduction of a CBCT technique: dual-phase CBCT (DP-CBCT) improves intra-arterial HCC treatment with drug-eluting beads (DEB-TACE). DP-CBCT can be used to localize liver tumors with the diagnostic accuracy of multi-phasic multidetector computed tomography (M-MDCT) and contrast enhanced magnetic resonance imaging (CE-MRI) (See the tumor), to guide intra-arterially guidewire and microcatheter to the desired location for selective therapy (Reach the tumor), and to evaluate treatment success during the procedure (Treat the tumor). The purpose of this manuscript is to illustrate how DP-CBCT is used in DEB-TACE to see, reach, and treat HCC.

Dual-phase cone-beam computed tomography (DP-CBCT) is a useful intraprocedural imaging technique for transarterial chemo-embolization treatment with drug-eluting beads of hepatocellular carcinoma. DP-CBCT has been used to perform three major steps in oncologic interventional radiology: tumor localization (see), navigation and intraprocedural catheter guidance (reach), and intraprocedural evaluation of treatment success (treat).

双相位锥束CT看看，到达，并在药物洗脱珠Transarterial化疗栓塞治疗原发性肝癌

The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 ...

医学

Application of Hemostatic Devices in Laparoscopic Hepatectomy

Laparoscopic hepatectomy is considered a conventional method for treating benign and malignant liver diseases because it is a minimally invasive method. Despite its non-invasive aspect, bleeding and bile leakage occur in liver parenchyma tissue resection during the operation or in the post-operation period, indicating the requirement for high-grade hemostatic devices, such as ultrasonic surgical aspiration, bipolar electrocoagulation, etc. The lack of availability of these high-grade hemostatic devices prevents laparoscopic hepatectomy from becoming a generalized procedure in basic medical organizations. In view of the situation mentioned above, a suite of simple and easy hemostatic devices is developed in this protocol, which includes a harmonic scalpel, monopole electrocoagulation, and a single lumen catheter, to innovatively perform liver parenchyma tissue resection. First of all, the porta hepatis or hepatic pedicle is occluded intermittently by a single lumen catheter, followed by clamping for 15 min and releasing for 5 min. Subsequently, using the harmonic scalpel, clamping and crushing of the liver are done to cut off the hepatic parenchyma tissue and to reveal the intrahepatic arteries, veins, and bile ducts. Lastly, the bleeding spots are coagulated by using monopole electrocoagulation at each spot. Intrahepatic pipeline structures are then visible by using these methods, which could stop bleeding easily, reduce the incidence rate of bile leakage, and improve the safety and feasibility of laparoscopic hepatectomy. Therefore, the simple and easy hemostatic devices shown here are suitable for conducting procedures in primary medical institutions.

High-grade hemostatic devices are essential for laparoscopic hepatectomy. However, these devices are not generalized in basic medical organizations. Therefore, a suite of simple and easy hemostatic devices is shown in this article, which can make the laparoscopic hepatectomy easier to perform.

止血装置在腹腔镜肝切除术中的应用

Laparoscopic hepatectomy is considered a conventional method for treating benign and malignant liver diseases because it is a minimally invasive method. ...

Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2).
A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.&#160; The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor&#8217;s portal vein was carried out via the recipient&#8217;s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient&#8217;s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7
In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3&#177;0.8 g to 9.8&#177;1 g. At this time, the graft&#8217;s weight decreased from 3.3&#177;0.8 g to 2.3&#177;0.8 g.
We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates.

Auxiliary liver transplantation provides a temporary support in acute hepatic failure, until regeneration of the failing liver. The heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) renders sufficient liver function. We developed an analogous technique in the rat, to examine the influence of the portal vein arterialization on the morphology and function of the graft.

在急性肝衰竭异位辅助性大鼠肝移植流量调节门静脉动脉

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the ...

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and evaluate novel therapeutic approaches. Non-invasive whole-body imaging using positron emission tomography (PET) provides critical insights into the in vivo characteristics of tissues at the molecular level in real-time. We present here a protocol for orthotopic HCC xenograft creation with and without hepatic artery ligation (HAL) to induce tumor hypoxia and the assessment of their tumor metabolism in vivo using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG) PET/magnetic resonance (MR) imaging. Tumor hypoxia could be readily visualized using the hypoxia marker [18F]FMISO, and it was found that the [18F]FMISO uptake was higher in HCC mice that underwent HAL than in the non-HAL group, whereas [18F]FDG could not distinguish tumor hypoxia between the two groups. HAL tumors also displayed a higher level of hypoxia-inducible factor (HIF)-1&#945; expression in response to hypoxia. Quantification of HAL tumors showed a 2.3-fold increase in [18F]FMISO uptake based on the standardized value uptake (SUV) approach.

Here, we present a protocol to create orthotopic hepatocellular carcinoma xenografts with and without hepatic artery ligation and perform non-invasive positron emission tomography (PET) imaging of tumor hypoxia using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG).

肝细胞癌原位小鼠模型中的无创PET/MR成像

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and ...

Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation.
In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.

Here, we present a protocol how to perform an isolated liver perfusion (IHP) with melphalan and we also discuss IHP as a treatment option for liver metastases of uveal melanoma.

隔离肝脏灌注作为治疗葡萄膜黑色素瘤肝转移

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic ...

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy ALPPS Procedure

Inducing rapid liver hypertrophy using Associating Liver Partition and Portal vein ligation for a Staged hepatectomy (ALPPS) has been proposed for resection of borderline resectable liver tumors. This model may elucidate mechanisms involved in rapid hypertrophy and allows testing of drugs that promote or block the acceleration of regeneration.

肝分型与门静脉结扎大鼠分期肝切除 (ALPPS) 手术模型的建立

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver ...

Application of Laparoscopic Hepatectomy Combined with Intraoperative Microwave Ablation in Colorectal Cancer Liver Metastasis

Laparoscopic hepatectomy is a common treatment for colorectal cancer liver metastasis. Previously, a sufficient number of functional liver masses had to be maintained during laparoscopic hepatectomy, with a residual liver volume of &gt;40% in cirrhotic patients and &gt;30% in non-cirrhotic patients. The high incidence of complications such as bleeding, bile leakage, or liver failure due to the exposure and difficulty of the resection of specific liver segments such as S2 and S7 reduces the success rate of liver resection. At present, microwave ablation is mainly applied in the treatment of liver metastasis using a percutaneous approach, which makes it difficult to identify hidden parts or small lesions. For some liver segments, the percutaneous puncture of liver segment 7 (S7) is likely to pass through the thoracic cavity, and the percutaneous puncture of liver segment 2 (S2) adjacent to the diaphragm is likely to injure the diaphragm and heart; these issues restrict the application of percutaneous ablation in colorectal cancer liver metastasis. Considering multiple lesions, laparoscopic microwave ablation combined with hepatectomy was performed in this study. The location of the lesions was determined by contrast-enhanced ultrasound under laparoscopy, and small lesions that were difficult to detect before the operation were identified. For the scattered lesions, which had diameters less than 3 cm and were difficult to resect, ablation was adopted to substitute hepatectomy. This technique helped to more explicitly locate the tumors, simplified the operation procedures, reduced the risk of complications such as bleeding and bile leakage, shortened the operation time, accelerated the postoperative recovery, significantly improved the success rate of operation, and enhanced the clinical prognosis of colorectal cancer liver metastasis by surgical resection.

This protocol describes the laparoscopic resection of colorectal cancer liver metastases combined with ultrasound-guided microwave ablation. This technique can safely, effectively, and accurately treat refractory liver metastases &lt;3 cm, reduce postoperative complications, and accelerate the postoperative rehabilitation of patients.

腹腔镜肝切除术联合术中微波消融术在结直肠癌肝转移中的应用

Laparoscopic hepatectomy is a common treatment for colorectal cancer liver metastasis. Previously, a sufficient number of functional liver masses had to ...

<meta charset="utf8"></head><body>在分期肝切除术动物模型中研究 ALLPS 的肝脏再生

A Mouse Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Procedure Aided by Microscopy

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative mortality, severely impacting patient outcomes. In a robust hepatic environment, the future liver remnant (FLR) must exceed 25%, and in cases of cirrhosis, this requirement increases to over 40%. The inadequacy of FLR is currently a major obstacle in the progression of hepatic surgery.
Traditional methods to enhance FLR hypertrophy mainly focus on portal vein embolization (PVE), but its effectiveness is considerably limited. In recent years, there have been numerous reports on a novel biphasic hepatectomy method involving hepatic partitioning and portal vein ligation, known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). ALPPS surpasses PVE in efficiently and considerably inducing FLR hypertrophy. However, the detailed mechanisms driving ALPPS-facilitated hepatic regeneration are not fully understood. Thus, replicating ALPPS in animal models is crucial to thoroughly investigate the molecular mechanisms of hepatic regeneration, offering valuable theoretical and practical insights.

<meta charset="utf8"></head><body>作者聚焦：通过 ALPPS 小鼠模型推进肝脏再生研究

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has been shown to result in remarkable liver regeneration after several weeks post first-stage surgery. Animal models that have undergone ALPPS have been developed to explore potential liver regeneration ability and achieve favorable clinical outcomes.

显微镜辅助分期肝切除术的关联肝分区和门静脉结扎的小鼠模型

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative ...

经皮肝脏灌注（PHP）与美法仑作为囿于肝脏不能手术切除转移的治疗

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肝细胞癌患者的跨径向获取化疗

双相位锥束CT看看，到达，并在药物洗脱珠Transarterial化疗栓塞治疗原发性肝癌

止血装置在腹腔镜肝切除术中的应用

在急性肝衰竭异位辅助性大鼠肝移植流量调节门静脉动脉

肝细胞癌原位小鼠模型中的无创PET/MR成像

隔离肝脏灌注作为治疗葡萄膜黑色素瘤肝转移

肝分型与门静脉结扎大鼠分期肝切除 (ALPPS) 手术模型的建立

腹腔镜肝切除术联合术中微波消融术在结直肠癌肝转移中的应用

显微镜辅助分期肝切除术的关联肝分区和门静脉结扎的小鼠模型

显微镜辅助分期肝切除术的关联肝分区和门静脉结扎的小鼠模型