Name: percutaneous hepatic perfusion (php) with melphalan as a treatment for unresectable metastases confined to the liver
Uploaded: 2016-07-31T14:00:00
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...

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	<li>Jovanovic, P., 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=Ocular+melanoma:+an+overview+of+the+current+status.">Ocular melanoma: an overview of the current status.</a> Int J Clin Exp Pathol. 6 (7), 1230-1244 (2013).</li><li>Taylor, I., Bennett, R., Sherriff, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+blood+supply+of+colorectal+liver+metastases.">The blood supply of colorectal liver metastases.</a> Br J Cancer. 38 (6), 749-756 (1978).</li><li>van de Velde, C. 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L., 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+perfusion+for+unresectable+isolated+hepatic+metastases+from+sarcoma.">Chemosaturation with percutaneous hepatic perfusion for unresectable isolated hepatic metastases from sarcoma.</a> Cardiovasc Intervent Radiol. 35 (6), 1480-1487 (2012).</li><li>Kandarpa, K., Machan, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Handbook of Interventional Radiologic Procedures. , 269-270 (2011).</li><li>Hofmann, H., 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=Unresectable+isolated+hepatic+metastases+from+solid+pseudopapillary+neoplasm+of+the+pancreas:+a+case+report+of+chemosaturation+with+high-dose+melphalan.">Unresectable isolated hepatic metastases from solid pseudopapillary neoplasm of the pancreas: a case report of chemosaturation with high-dose melphalan.</a> Pancreatology. 14 (6), 546-549 (2014).</li><li>Miao, N., 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=Percutaneous+hepatic+perfusion+in+patients+with+metastatic+liver+cancer:+anesthetic,+hemodynamic,+and+metabolic+considerations.">Percutaneous hepatic perfusion in patients with metastatic liver cancer: anesthetic, hemodynamic, and metabolic considerations.</a> Ann Surg Oncol. 15 (3), 815-823 (2008).</li><li>Vogl, T. 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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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<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 border="0" cellpadding="0" cellspacing="0" width="1115">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:411px;">Delcath 2nd Generation Hepatic CHEMOSAT Delivery System&#160;</td>
			<td style="width:357px;">Delcath Systems Inc., New York, New York, USA</td>
			<td style="width:180px;">602001 and 602002</td>
			<td style="width:167px;">Item no. 1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isofuse Isolation Aspiration Catheter (Double Balloon Catheter)</td>
			<td>Delcath Systems Inc., New York, New York, USA</td>
			<td></td>
			<td rowspan="2">Item no. 1a</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">10F Venous Return Catheter</td>
			<td>Delcath Systems Inc., New York, New York, USA</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Hemofiltration Cartridges</td>
			<td>Delcath Systems Inc., New York, New York, USA</td>
			<td></td>
			<td rowspan="2">Item no. 1b</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Circuit components</td>
			<td>Delcath Systems Inc., New York, New York, USA</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Level-1 rapid fluid management system</td>
			<td style="width:357px;">Smiths Medical</td>
			<td style="width:180px;"></td>
			<td>Item no. 2</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">22G arterial line&#160;</td>
			<td style="width:357px;">Arrow International Inc. /&#160; Teleflex Inc.,Dublin, Ireland</td>
			<td style="width:180px;"></td>
			<td>Item no. 3</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Vigileo, Monitor</td>
			<td>Edwards Lifesciences Corp, Irvine, California, USA</td>
			<td style="width:180px;"></td>
			<td>Item no. 4</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7.5F Triple lumen intravenous catheter, 20 cm&#160;</td>
			<td>Vygon, Valkenswaard, Nederland</td>
			<td></td>
			<td>Item no. 5</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">5F sheath&#160;</td>
			<td style="width:357px;"></td>
			<td style="width:180px;"></td>
			<td>Item no. 6</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">2.7 Progreat microcatheter&#160;</td>
			<td>Terumo, Tokyo, Japan</td>
			<td>MC-PP27131</td>
			<td>Item no. 7</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">18F sheath&#160;</td>
			<td style="width:357px;"></td>
			<td style="width:180px;"></td>
			<td>Item no. 8</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;">Auto-injector Medrad Mark V ProVis</td>
			<td>Bayer, Indianola, Pennsylvania, USA</td>
			<td style="width:180px;">Not available anymore, replaced by&#160;Medrad&#160;Mark 7 Arterion&#160;Injection System</td>
			<td>Item no. 9</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Melphalan</td>
			<td>Alkeran, Aspen Pharmacare, Dublin, Ireland</td>
			<td style="width:180px;"></td>
			<td>Item no. 10</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Heparin LEO, 5000 IE/ml</td>
			<td style="width:357px;">LEO Pharma AB, Denmark</td>
			<td style="width:180px;"></td>
			<td>Item no. 11</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Centrifugal pump</td>
			<td style="width:357px;">Medtronic, Minneapolis, Minnesota, VS</td>
			<td style="width:180px;"></td>
			<td>Item no. 12</td>
		</tr>
		<tr height="21">
			<td colspan="2" height="21" style="height:21px;">Voluven colloid solution (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection)</td>
			<td style="width:180px;"></td>
			<td>Item no. 13</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Iopromide 300, Ultravist</td>
			<td style="width:357px;">Bayer, Indianola, Pennsylvania, USA</td>
			<td style="width:180px;"></td>
			<td>Item no. 14</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Detachable coil, Interlock</td>
			<td style="width:357px;">Boston Scientific, Marlborough, Massachusetts, USA</td>
			<td style="width:180px;"></td>
			<td>Item no. 15</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:411px;">Vascular plug, Amplatzer 4</td>
			<td style="width:357px;">St. Jude Medical, St Paul,Minnesota, USA</td>
			<td style="width:180px;"></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 ...

Research

JoVE Journal

Medicine

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

The Measurement and Treatment of Suppression in Amblyopia

测量和制止在弱视治疗

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

科研

医学

Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction

部分原位肝移植大鼠模型的肝动脉重建的外科手术

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as ...

Osmotic Drug Delivery to Ischemic Hindlimbs and Perfusion of Vasculature with Microfil for Micro-Computed Tomography Imaging

药物输送到微型计算机断层扫描成像缺血后肢血管灌注与微滤渗透

Preclinical research in animal models of peripheral arterial disease plays a vital role in testing the efficacy of therapeutic agents designed to ...

A Preclinical Murine Model of Hepatic Metastases

肝转移的临床前小鼠模型

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, ...

Isolated Hepatic Perfusion as a Treatment 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 ...

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

直接节段性肝内交付使用大鼠肝门部夹具模型方法

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ...

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

内靶容积法治疗肝转移瘤的立体定向体放疗

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For ...

A Small Animal Model of Ex Vivo Normothermic Liver Perfusion

A Small Animal Model of Ex Vivo Normothermic Liver Perfusion

体外常温肝灌注的小动物模型

There is a significant shortage of liver allografts available for transplantation, and in response the donor criteria have been expanded. As a result, ...

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy

肝静脉压梯度和转性肝活检测量

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced ...

Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology

毛利精密切肝片作为肝脏生物学的Ex Vivo模型

Understanding the mechanisms of liver injury, hepatic fibrosis, and cirrhosis that underlie chronic liver diseases (i.e., viral hepatitis, non-alcoholic ...