Lennart Wiman (photographer) is acknowledged for excellent video recording.

患者は、インフォームドコンセントを書かれて提供され、研究はヨーテボリ大学の地方倫理審査委員会によって承認された。 1.麻酔<ol><li>すべての監視（ECG、血圧カフ）17を設定します。 </li><li>半ば胸椎レベル17に下に硬膜外カテーテルを挿入します。 </li><li>プロポフォール2mg / kgの、フェンタニル150μgの、及びロクロニウム0.6 mgの麻酔を誘導/以前に挿入末梢静脈カテーテルを通してキロ。 </li><li> Preoxygenateとは、患者に挿管。セボフルラン、酸素と空気17との麻酔を維持。 </li><li>ダブルルーメン中心静脈カテーテルおよび動脈カテーテルを挿入します。 CVPと動脈圧17を監視します。 </li></ol>船舶の肝臓とカニューレ挿入の2の分離<ol><li>ヘパリンの100 IE / kgを投与し、抗生物質の予防に（与える例えば 、トリメトプリム及び80の160 mgのスルファメトキサゾールの0ミリグラム）。 </li><li>経皮的セルジンガー法を用いて、大腿静脈で17 Frのカテーテルおよび外頸静脈18で15 Frのカテーテルを配置。蛍光透視法によりカテーテルの位置を確認してください。 </li><li>正中ダウン剣状突起からL字型の切開により開腹を実行してから、右肋骨下切開19に拡張。 </li><li>余分-肝転移が完了検査や触診により腹部に存在しないことを確認します。 <ol><li>疑わしい病変が見つかった場合は、凍結切片による悪性腫瘍を確認。 </li><li>肝外症状（periaortalリンパ節腫脹、腹部転移）の証拠がある場合の手順を終了します。肝門部リンパ節腫脹は禁忌とはみなされません。 </li></ol></li><li>鎌状靱帯、左右の三角靱帯および冠状靭帯19を分割することにより肝臓を動員する。 </li><li>大静脈を解剖後腹膜支流静脈の結紮と横隔膜までの腎静脈から始まる静脈。 </li><li>右副腎静脈を識別し、その周りに血管ループを配置します。 </li><li>右性腺静脈を識別します。 5〜10センチメートルのためにそれを分析。大静脈への入り口の周りに巾着縫合を置きます。 <ol><li>性腺静脈に遠位に合字を置きます。はさみを使用して、大静脈から性腺静脈3〜5センチメートルを開きます。 </li><li>右性腺静脈から18 Frのワイヤー補強カテーテルを挿入し、retrohepatically腎静脈の上にチップを置く。 </li><li>カテーテルの位置を固定するために性腺静脈を中心に合字を置きます。 </li><li>カテーテルを通る血液の戻りを確認します。カテーテル18を Heparinize。 </li></ol></li><li>肝十二指腸間膜を解剖し、総肝動脈、胃十二指腸動脈と固有肝動脈を可視化する。 <ol><li>置き容器は総肝アルテの周りにループRYとgastrodoudenal動脈。 </li><li>門脈を分析し、その周りに血管ループを配置します。 </li><li>総胆管を含む靱帯の残りの部分を分離し、血管ループでこのすべてを含む。 </li></ol></li><li>血管ループと胃十二指腸動脈を持ち上げます。動脈流入を中断した後、ハ​​サミを使って切開する。 <ol><li>固有肝動脈内にその先端に8-12 Frのカテーテルを挿入します。胃十二指腸動脈の周りの合字で位置を固定します。 </li><li>カテーテル内の血液の戻りを確認し、18それをheparinize。 </li></ol></li><li>プライムパック赤血球の一単位、アルブミン100mlの（が50g / L）、Tribonat（重炭酸ナトリウム）、ヘパリン2500単位（5000 IE / ml）を100mlおよびクリスタ250mlの灌流システム。 </li><li>ローラーポンプを備えた人工心肺からなる灌流システムとヒータtまで動脈および大静脈カテーテルを接続する使い捨てタイプの静脈リザーバー、人工肺及び管システムとのogether。 </li><li>ヒーターユニットと一緒に、遠心ポンプからなる静静脈バイパスポンプに大腿骨と外頸静カテーテルを接続し、バイパスを開始します。 </li><li> infrahepatically腎静脈の上大静脈の周りRumelの止血帯を締めるとsuprahepatically Klintmalm血管クランプを使用して大静脈をクランプすることにより、肝臓の分離を完了します。 <ol><li>総胆管、門脈と右副腎静脈の周りにRumelの止血帯を締め、最後に血管クランプを用いて肝動脈をクランプ。 </li></ol></li></ol> 3.灌流<ol><li>灌流を起動し、手動で静脈リザーバ内の血中濃度を監視する。定常状態レベルは500-1,200 ml /分の間、通常の流量に到達するまでの流量を調整する。 </li><li>左右の肝葉にサーミスタプローブを配置し、直接1に動脈カテーテル。 </li><li> 40℃。目標肝臓温度を目指し灌流液を加熱灌流を通じてこの温度を保つ。 </li><li>静静脈バイパスポンプヘッド上のシンチレーションプローブを配置します。 </li><li>循環に10 MBqの99m Tc でアルブミン（1ml）中の少量を注入することにより、漏洩監視システムを較正し、ベースラインの活動を登録する。 <ol><li>肝灌流ユニットに、10倍高い用量の、100 MBqのの99m Tc で -アルブミン（1ミリリットル）を注入します。 </li><li>シンチレーションプローブによって測定された活性の増加などの全身循環への灌流システムからの漏れを記録します。 </li><li>静脈リザーバ内の体積の増加として灌流システムに全身循環からの漏れを記録します。 </li></ol></li><li>流量の定常状態が確立されると、漏れが存在しないと肝臓の温度が40℃に達したの用量でメルファランを注入潅流システムには1mg / kg体重が離れて30分ある二回に分け。 </li></ol> 4.灌流を終了し、カテーテルを削除<ol><li>灌流の60分後、システムからの灌流液を空にし、クリスタの千ミリリットルで肝臓を灌漑。 </li><li> 、灌流ユニットにパックされた赤血球の1単位の追加肝臓に注入した後、灌流を停止する。 </li><li> Klintmalmクランプと大静脈からRumelの止血帯を離します。 </li><li>肝十二指腸間膜からRumelの止血帯を離します。 </li><li>胃十二指腸動脈から合字を削除します。カテーテルを取り外し、容器を連結する。 </li><li>肝動脈からのクランプを解除してください。 </li><li>性腺静脈からカテーテルを外し、容器を連結する。 </li><li>静脈静脈バイパスポンプを停止し、チューブを外します。 </li><li>中断のない筋膜縫合した後、皮内、皮膚の縫合糸で腹部を閉じます。 </li><li> Cを削除大腿骨におけるathetersと外頚静脈と5分間局所的な圧力を加える。 </li></ol> 5.術後ケア<ol><li>患者を抜管し、24時間の術後治療室に移す。中心静脈圧、および動脈圧を監視続ける。 </li><li>術後のケアの3-7日の典型的なのための外科部門に患者を転送します。 </li><li> 4週間の合計5000 IE /日の用量で、低分子量ヘパリン（LMWH）を続ける。 </li></ol>

<ol>
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The authors have nothing to disclose.

転移性ブドウ膜黒色腫の患者は、いくつかの治療オプションがあります。化学療法6、免疫療法23と標的療法24は、改良されたOSを表示することができていない。いくつかの肝転移を有する患者では、肝切除がオプション12である。他の治療は、肝動脈内化学療法（HIA）9、動脈化学塞栓療法（TACE）25と選択的内部放射線療法（SIRT）26が含?...

ブドウ膜黒色腫は、発生率は白人集団1で最高であることと、成人で最も一般的な原発眼内悪性腫瘍である。局所治療は、摘出またはローカルプラーク放射線療法2,3で構成されています。関係なく、局所治療の、転移性疾患は、最終的には患者4,5の約百分の35から50に展開していきます。肝臓は、最も一般的な転移の部位および単離された肝転移を有する本患者の約50％である。肝転移を有する患者についての全生存期間の中央値（OS）は6〜12ヶ月4です。いくつかの異なる全身および地域の治療戦略が検討されているが、生存率が2を改善していない。 全身化学療法を用いた治療、両方の単一物質（ダカルバジンまたはテモゾロミド6）または併用療法（BOLD養生7、トレオスルファン8とゲムシタビン）が、その後以下の回答率を示している10％。肝動脈内化学療法（HIA）は、全身化学療法に比べてわずかに高い奏効率が、全体的な生存9の増加は示されています。シスプラチンとカルボプラチンと動脈化学塞栓療法（TACE）は、9ヶ月10の生存期間中央値の患者の57パーセントの部分的応答を示した。選択的内部照射療法（SIRT）は、7ヵ月11の生存期間中央値を有する患者の62％の部分的応答を示した。 255患者を含む肝切除術の研究では、14ヶ月の全生存が報告された。顕微鏡的に完全切除が可能であった患者の76で、生存率は27ヶ月12だった。 孤立した肝灌流（I​​HP）は、もともとはライアンとAusmanによって開発された地域の治療オプション、です。技術の背後にある理論的根拠は、外科的に分離して全身を回避しながら、化学療法剤の高用量で肝臓を灌流することであるxicity 13。また、同時温熱腫瘍血流および細胞膜透過性14の変化による化学療法剤の取り込みの増加を媒介する。完全な血管の単離は、のTc-99を使用して、放射性トレーサー法を用いて確認されたヒト血清アルブミン15とラベル。レトロスペクティブ第II相試験は、スウェーデン16におけるブドウ膜黒色腫の肝転移との最長生存者に比べてIHPを受けた患者のための14ヶ月（26対12ヶ月）の潜在的な生存利益を示している。 ここでは、現在の結果と今後の展望の短い口コミをIHPの手法を提示する。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Wire re-inforced catethers</td>
			<td>Medtronic Inc, Minnesota, USA</td>
			<td></td>
			<td>12-18Fr</td>
		</tr>
		<tr>
			<td>St&#246;ckert S5</td>
			<td>Sorin Group, Mirandola, Italy</td>
			<td></td>
			<td>Heart-lung machine</td>
		</tr>
		<tr>
			<td>Rotaflow</td>
			<td>Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany</td>
			<td></td>
			<td>Centrifugal pump</td>
		</tr>
		<tr>
			<td>HU 35</td>
			<td>Maquet cardiopulmonary AG, Hirrlingen, Germany</td>
			<td></td>
			<td>Heater unit</td>
		</tr>
		<tr>
			<td>Flexbumin 200 g/l</td>
			<td>Baxter Medical AB, Kista, Sweden</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tribonat</td>
			<td>Fresenius Kabi AB, Uppsala, Sweden</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Heparin LEO, 5000 IE/ml</td>
			<td>LEO Pharma AB, Sweden</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ringer Acetate</td>
			<td>Baxter Medical AB, Kista, Sweden</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Vasculosis</td>
			<td>Cis-Bio International, Gif-Sur-Yvette, France</td>
			<td></td>
			<td>99mTc-albumin</td>
		</tr>
		<tr>
			<td>MedicView</td>
			<td>SystemData AB, Gothenburg, Sweden</td>
			<td></td>
			<td>Leakage monitoring system</td>
		</tr>
		<tr>
			<td>Alkeran</td>
			<td>Aspen Europe GmbH, Bad Oldesloe, Germany</td>
			<td></td>
			<td>melphalan</td>
		</tr>
	</tbody>
</table>

isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma

孤立した肝灌流（I​​HP）は、肝臓を外科的に単離され、化学療法剤のメルファランの高濃度で灌流されている手順です。簡単に言えば、手順は外頸静脈に大腿静脈からの経皮静脈静脈バイパスのセットアップから始まります。開腹を経由して、カテーテルは、その後、適切な肝動脈および大静脈に挿入されます。 supra-とinfrahepatically両方門脈と大静脈は、その後クランプされる。動脈および静脈カテーテルは、心臓、肺機に接続され、肝臓で60分間、メルファラン（1 mg / kg体重）で灌流される。この方法には、局所的に、全身循環に漏れることなく、化学療法剤の高用量で肝臓を灌流することが可能である。 ブドウ膜黒色腫の摘出肝臓転移を有する患者を含む以前の研究では、33から100パーセントの全体的な応答率と9と13ヶ月の間に生存期間の中央値、報告されている。このプロトコルの目的は、手順を実行する方法の明確な説明を与えることとブドウ膜黒色腫の肝転移に対する治療選択肢としてIHPを議論することである。

最初の報告は、TNF-αの有無にかかわらずファランで処置した22人の患者が含まれていた。結果は、2つのCR（10％）の患者、および11ヶ月20の全生存期間中央値を含む62パーセントの全体的な応答率を示した。その後の研究だけではメルファランを使用して治療29連続した患者の結果に報告した。結果は、10％の完全寛解と12ヶ月21の生存期間中央値を含む62パーセントの全体的なレ?...

Watch this Scientific Journal Video about Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma at JoVE.com

Isolated Hepatic Perfusion as a Treatment 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.

ブドウ膜黒色腫の肝転移の治療として単離した肝灌流

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

isolated-hepatic-perfusion-as-treatment-for-liver-metastases-uveal

Research

JoVE Journal

Medicine

13.3K ビュー.  Institute of Clinical Sciences. 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.

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

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

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as studies on graft preservation and ischemia-reperfusion injury 1,2, immunological responses 3,4, hemodynamics 5,6, and small-for-size syndrome 7. The rat OLT is among the most difficult animal models in experimental surgery and demands advanced microsurgical skills that take a long time to learn. Consequently, the use of this model has been limited. Since the reliability and reproducibility of results are key components of the experiments in which such complex animal models are used, it is essential for surgeons who are involved in rat OLT to be trained in well-standardized and sophisticated procedures for this model.
While various techniques and modifications of OLT in rats have been reported 8 since the first model was described by Lee et al. 9 in 1973, the elimination of the hepatic arterial reconstruction 10 and the introduction of the cuff anastomosis technique by Kamada et al. 11 were a major advancement in this model, because they simplified the reconstruction procedures to a great degree. In the model by Kamada et al., the hepatic rearterialization was also eliminated. Since rats could survive without hepatic arterial flow after liver transplantation, there was considerable controversy over the value of hepatic arterialization. However, the physiological superiority of the arterialized model has been increasingly acknowledged, especially in terms of preserving the bile duct system 8,12 and the liver integrity 8,13,14.
In this article, we present detailed surgical procedures for a rat model of OLT with hepatic arterial reconstruction using a 50% partial graft after ex vivo liver resection. The reconstruction procedures for each vessel and the bile duct are performed by the following methods: a 7-0 polypropylene continuous suture for the supra- and infrahepatic vena cava; a cuff technique for the portal vein; and a stent technique for the hepatic artery and the bile duct.

Orthotopic liver transplantation in rats is an indispensable experimental model for biomedical research. Here we present our surgical procedures for orthotopic rat liver transplantation with hepatic arterial reconstruction using a 50% partial graft.

肝動脈再建を用いた部分同所性肝移植のラットモデルのための外科的処置

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

医学

A Preclinical Murine Model of Hepatic Metastases

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, murine pancreatic tumor model of hepatic metastases via a hemispleen injection of syngeneic murine pancreatic tumor cells is described. This model mimics many of the clinical conditions in patients with metastatic disease to the liver. Mice consistently develop metastases in the liver allowing for investigation of the metastatic process, experimental therapy testing, and tumor immunology research.

A preclinical, murine model of hepatic metastases performed via a hemispleen injection technique.

肝転移の前臨床マウスモデル

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

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

治療抵抗性大うつ病性障害の治療薬としてdmPFC-のrTMSをMRIガイド

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial ...

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

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

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

In this manuscript, we describe percutaneous isolated hepatic perfusion with simultaneous chemofiltration as treatment for unresectable liver metastases. This procedure is performed under general anaesthesia in the angiosuite by an experienced team, consisting of an interventional radiologist, a clinical perfusionist and anaesthesiologist.

肝臓に閉じ込められた切除不能な転移の治療として、メルファランとの経皮肝灌流（PHP）

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

Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells

A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in which the liver has been repopulated with functional human hepatocytes, could serve as a useful tool for investigating human hepatic cell biology, drug metabolism, and other preclinical applications. One of the key factors required for successful transplantation of human hepatocytes into mice is the elimination of the endogenous hepatocytes to prevent competition with the human cells and provide a suitable space and microenvironment for promoting human donor cell expansion and differentiation. To date, two major liver injury mouse models utilizing fumarylacetoacetate hydrolase (Fah) and uroplasminogen activator (uPA) mice have been established. However, Fah mice are used mainly with mature hepatocytes and the application of the uPA model is limited by decreased breeding. To overcome these limitations, Alb-toxin receptor mediated cell knockout (TRECK)/SCID mice were used for in vivo differentiation of immature human hepatocytes and humanized liver generation. Human hepatic stem cells (HpSCs) successfully repopulated the livers of Alb-TRECK/SCID mice that had developed lethal fulminant hepatic failure following diphtheria toxin (DT) treatment. This model of a humanized liver in Alb-TRECK/SCID mice will have functional applications in studies involving drug metabolism and drug-drug interactions and will promote other in vivo and in vitro studies.

Here, we present a novel humanized mouse liver model generated in Alb-toxin receptor mediated cell knockout (TRECK)/SCID mice following the transplantation of immature and expandable human hepatic stem cells.

ヒト肝幹細胞を用いたヒト化マウス肝臓の生成

A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in ...

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

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.

A unique rat liver hilar clamp model was developed for studying the impact of pharmacologic molecules in ameliorating ischemia-reperfusion injury. This model includes direct cannulation of the portal supply to the ischemic liver segment via a branch of the portal vein, allowing for direct hepatic delivery.

ラット肝臓肝門部クランプモデルを用いたダイレクトセグメント別肝臓内送達方法

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

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For inoperable patients, local ablation therapies, such as stereotactic body radiotherapy (SBRT), can provide effective local tumor control with minimal toxicity. Because of its high precision and accuracy, SBRT delivers a higher radiation dose per fraction, is more effective, and targets smaller irradiation volumes than does conventional radiotherapy. In addition, steep dose gradients from target lesions to surrounding normal tissues are achieved using SBRT; thus, SBRT provides more effective tumor control and exhibits fewer side effects than conventional radiotherapy. The use of SBRT is prevalent for treating intracranial lesions (known as stereotactic radiosurgery); however, it is now also used for treating spinal and adrenal metastases. Because of advancements in image-guided assistance and respiratory motion management, several studies have investigated the use of SBRT for treating lung or liver tumors, which move as a patient breathes. The results of these studies have suggested that SBRT favorably controls tumors in the case of moving lesions.
Four-dimensional computed tomography (4D-CT) with an abdominal compressor (AC) is clinically convenient for effective respiratory motion management. Because this method is noninvasive and allows free breathing, its use reduces complications. Furthermore, patients consider this method convenient. Moreover, it is considered more efficient than other methods of respiratory motion management by physicians and therapists. The use of 4D-CT with an AC for treating pulmonary lesions has also been widely investigated, and the technique is gaining acceptance for treating hepatic lesions. However, the protocols for using 4D-CT with an AC for treating hepatic lesions are different from those used for treating pulmonary lesions. In this article, we describe a new protocol for SBRT with 4D-CT and an AC for treating liver metastases.

Stereotactic body radiotherapy (SBRT) requires rigorous accuracy and precision for delivering high radiation doses per fraction to small treatment volumes to improve tumor control and simultaneously reduce toxicity. Herein, we present a noninvasive and clinically convenient respiratory motion management protocol for SBRT for liver metastases.

体幹部定位放射線照射のため内部のターゲット ボリュームによる肝転移の治療

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

There is a significant shortage of liver allografts available for transplantation, and in response the donor criteria have been expanded. As a result, normothermic ex vivo liver perfusion (NEVLP) has been introduced as a method to evaluate and modify organ function. NEVLP has many advantages in comparison to hypothermic and subnormothermic perfusion including reduced preservation injury, restoration of normal organ function under physiologic conditions, assessment of organ performance, and as a platform for organ repair, remodeling, and modification. Both murine and porcine NEVLP models have been described. We demonstrate a rat model of NEVLP and use this model to show one of its important applications &#8212; the use of a therapeutic molecule added to liver perfusate. Catalase is an endogenous reactive oxygen species (ROS) scavenger and has been demonstrated to decrease ischemia-reperfusion in the eye, brain, and lung. Pegylation has been shown to target catalase to the endothelium. Here, we added pegylated-catalase (PEG-CAT) to the base perfusate and demonstrated its ability to mitigate liver preservation injury. An advantage of our rodent NEVLP model is that it is inexpensive in comparison to larger animal models. A limitation of this study is that it does not currently include post-perfusion liver transplantation. Therefore, prediction of the function of the organ post-transplantation cannot be made with certainty. However, the rat liver transplant model is well established and certainly could be used in conjunction with this model. In conclusion, we have demonstrated an inexpensive, simple, easily replicable NEVLP model using rats. Applications of this model can include testing novel perfusates and perfusate additives, testing software designed for organ evaluation, and experiments designed to repair organs.

A Small Animal Model of Ex Vivo Normothermic Liver Perfusion

There is a significant liver donor shortage, and criteria for liver donors have been expanded. Normothermic ex vivo liver perfusion (NEVLP) has been developed to evaluate and modify organ function. This study demonstrates a rat model of NEVLP and tests the ability of pegylated-catalase, to mitigate liver preservation injury.

Ex Vivo常温肝灌流の小さな動物モデル

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

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced chronic liver disease followed by an instruction for transjugular biopsy. Under local anesthesia and ultrasound guidance, a catheter introducer sheath is placed in the right internal jugular vein. Using&#160;fluoroscopic guidance, a balloon catheter is advanced into the inferior vena cava (IVC) and inserted into a large hepatic vein. Correct and sufficient wedge position of the catheter is ensured by injecting contrast media while the balloon is blocking the outflow of the cannulated hepatic vein. After calibrating the external pressure transducer, continuous pressure recordings are obtained with triplicate recordings of the wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP). The difference between FHVP and WHVP is referred to as HVPG, with values &#8805;10 mm Hg indicating clinically significant portal hypertension (CSPH). Before removing the catheter, pressure readings obtained in the IVC at the same level, as well as the right atrial pressure are recorded.
Finally, a transjugular liver biopsy can be obtained via the same vascular route. Different systems are available; however, core biopsy needles are preferred over aspiration needles, especially for cirrhotic livers. Again, under fluoroscopic guidance a biopsy needle introducer sheath is advanced into an hepatic vein. Next, the transjugular biopsy needle is gently advanced through the introducer sheath: (i) in case of aspiration biopsy, the needle is advanced into the liver parenchyma under aspiration and then removed quickly, or (ii) in case of a core biopsy, the cutting-mechanism is triggered inside the parenchyma. Several separate passages can be safely performed to obtain sufficient liver specimens via transjugular biopsy. In experienced hands, the combination of these procedures takes about 30-45 min.

Here, we present a protocol for measurement of hepatic venous pressure gradient (HVPG),the gold standard to diagnose clinically significant portal hypertension. Moreover, we describe how to perform a transjugular liver biopsy within the same session.

肝静脈圧勾配と経頸部肝生検の測定

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

Understanding the mechanisms of liver injury, hepatic fibrosis, and cirrhosis that underlie chronic liver diseases (i.e., viral hepatitis, non-alcoholic fatty liver disease, metabolic liver disease, and liver cancer) requires experimental manipulation of animal models and in vitro cell cultures. Both techniques have limitations, such as the requirement of large numbers of animals for in vivo manipulation. However, in vitro cell cultures do not reproduce the structure and function of the multicellular hepatic environment. The use of precision-cut liver slices is a technique in which uniform slices of viable mouse liver are maintained in laboratory tissue culture for experimental manipulation. This technique occupies an experimental niche that exists between animal studies and in vitro cell culture methods. The presented protocol describes a straightforward and reliable method to isolate and culture precision-cut liver slices from mice. As an application of this technique, ex vivo liver slices are treated with bile acids to simulate cholestatic liver injury and ultimately assess the mechanisms of hepatic fibrogenesis.

This protocol provides a simple and reliable method for the production of viable precision-cut liver slices from mice. The ex vivo tissue samples can be maintained under laboratory tissue culture conditions for multiple days, providing a flexible model to examine liver pathobiology.

肝臓生物学のEx Vivoモデルとしてのマウス精密カット肝臓スライス

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