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

المرضى شريطة موافقة خطية مستنيرة وتمت الموافقة على الدراسة من قبل مجلس المراجعة الأخلاقية الإقليمي في جامعة غوتنبرغ. 1. التخدير <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إعداد كافة رصد (ECG، ضغط الدم صفعة) 17. </li><li style=";text-align:right;direction:rtl"> إدراج القسطرة فوق الجافية في أسفل إلى منتصف مستوى الصدري 17. </li><li style=";text-align:right;direction:rtl"> لحث التخدير مع البروبوفول 2 مغ / كغ، 150 ميكروغرام من الفنتانيل، وRocuronium 0.6 ملغ / كغ من خلال القسطرة الوريدية الطرفية إدراجها سابقا. </li><li style=";text-align:right;direction:rtl"> Preoxygenate وتدخله المريض. الحفاظ على التخدير مع سيفوفلوران والأكسجين والهواء 17. </li><li style=";text-align:right;direction:rtl"> اضافة الى وجود تجويف مزدوج القسطرة الوريدية المركزية وقسطرة الشرايين. مراقبة CVP والشرايين ضغط 17. </li></ol> 2. عزل الكبد والقسطرة السفن <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إدارة IE 100 / كغ من الهيبارين وإعطاء العلاج الوقائي بالمضادات الحيوية (على سبيل المثال، 160 ملغ من ميثوبريم و 800 ملغ من سلفاميثوكسازول). </li><li style=";text-align:right;direction:rtl"> باستخدام طريقة سيلدينغر عن طريق الجلد، ووضع 17 الاب قسطرة في الوريد الفخذي و15 الاب قسطرة في الوريد الوداجي الخارجي 18. التحقق من مواقف القسطرة عن طريق التنظير. </li><li style=";text-align:right;direction:rtl"> إجراء عملية فتح البطن عن طريق شق على شكل حرف L من عملية الخنجري أسفل خط الوسط ومن ثم امتدت إلى شق تحت الضلع الأيمن (19). </li><li style=";text-align:right;direction:rtl"> تحقق من أن لا الانبثاث خارج الكبد موجودة في البطن من قبل التفتيش الكامل والجس. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إذا تم العثور على أي آفات مشبوهة، تحقق من الورم الخبيث من قبل القسم المجمدة. </li><li style=";text-align:right;direction:rtl"> إنهاء الإجراء إذا كان هناك دليل على مظهر خارج الكبد (تضخم الغدد periaortal، الانبثاث في البطن). لا يعتبر اعتلال العقد اللمفية في الكبد بورتا موانع. </li></ol></li><li style=";text-align:right;direction:rtl"> تعبئة الكبد بقسمة الرباط المنجلي، في الرباط الثلاثي الأيسر والأيمن والشريان التاجي الرباط 19. </li><li style=";text-align:right;direction:rtl"> تشريح الأجوفيةالوريد ابتداء من الأوردة الكلوية حتى الحجاب الحاجز مع ربط الأوردة رافد خلف الصفاق. </li><li style=";text-align:right;direction:rtl"> تحديد الوريد الكظري الأيمن ووضع حلقة سفينة حوله. </li><li style=";text-align:right;direction:rtl"> تحديد الوريد الغدد التناسلية الصحيح. تشريح ذلك لمدة 5-10 سم. وضع خياطة محفظة سلسلة حول مدخل الوريد الأجوف. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> وضع رباط بشكل أقصى على المنوال الغدد التناسلية. باستخدام مقص، وفتح الغدد التناسلية الوريد 3-5 سم من الوريد الأجوف. </li><li style=";text-align:right;direction:rtl"> إدراج 18 الاب المقوى سلك القسطرة عن طريق الوريد الغدد التناسلية الصحيح ووضع طرف retrohepatically فوق الأوردة الكلوية. </li><li style=";text-align:right;direction:rtl"> وضع رباط حول الوريد الغدد التناسلية لتأمين موقف القسطرة. </li><li style=";text-align:right;direction:rtl"> تحقق من عودة الدم من خلال القسطرة. يعالج بالهيبارين القسطرة 18. </li></ol></li><li style=";text-align:right;direction:rtl"> تشريح الرباط الكبدي الإثناعشري وتصور الشريان الكبدي شيوعا، وهو الشريان معدي والشريان الكبدي السليم. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> سفينة مكان حلقات حول آرتي الكبدي شيوعاراي والشريان gastrodoudenal. </li><li style=";text-align:right;direction:rtl"> تشريح الوريد البابي ووضع حلقة سفينة حوله. </li><li style=";text-align:right;direction:rtl"> عزل بقية الرباط تحتوي على القناة الصفراوية المشتركة، وتشمل كل هذا في حلقة السفينة. </li></ol></li><li style=";text-align:right;direction:rtl"> رفع الشريان معدي مع حلقة السفينة. بعد انقطاع تدفق الشرايين، وجعل شق باستخدام المقص. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إدراج 8-12 الاب القسطرة مع طرفها في الشريان الكبدي السليم. تأمين موقف مع رباط حول الشريان معدي. </li><li style=";text-align:right;direction:rtl"> تحقق عودة الدم في القسطرة ثم يعالج بالهيبارين عليه 18. </li></ol></li><li style=";text-align:right;direction:rtl"> رئيس نظام الارواء مع وحدة واحدة من الكريات الحمراء معبأة، و 100 مل من الزلال (50 جم / لتر)، و 100 مل من Tribonat (بيكربونات الصوديوم)، 2500 وحدة من الهيبارين (5،000 IE / مل) و 250 مل من بلورانيات. </li><li style=";text-align:right;direction:rtl"> توصيل الشرايين والقسطرة الوريد الأجوف إلى نظام نضح تتألف من آلة الرئة القلب مجهزة بمضخة الأسطوانة وسخان رogether مع الخزان، مكساج وأنابيب أنظمة الوريدية من النوع القابل للتصرف. </li><li style=";text-align:right;direction:rtl"> ربط القسطرة الوداجي الفخذ والخارجية إلى مضخة تجاوز venovenous تتكون من مضخة طرد مركزي، جنبا إلى جنب مع وحدة سخان والبدء الالتفافية. </li><li style=";text-align:right;direction:rtl"> استكمال عزل الكبد من خلال تشديد وقف النزف Rumel حول الوريد الأجوف infrahepatically فوق عروق الكلى وتحامل على الوريد الأجوف suprahepatically باستخدام الأوعية الدموية المشبك Klintmalm. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> تشديد وقف النزف Rumel حول القناة الصفراوية المشتركة، الوريد البابي والوريد الكظري الأيمن والمشبك أخيرا الشريان الكبدي باستخدام المشبك الأوعية الدموية. </li></ol></li></ol> 3. الإرواء <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> بدء نضح يدويا ومراقبة مستوى الدم في الخزان الوريدي. ضبط معدل تدفق حتى يتم التوصل إلى مستوى ثابت للدولة، عادة ما يكون معدل التدفق بين 500-1،200 مل / دقيقة. </li><li style=";text-align:right;direction:rtl"> ضع تحقيقات الثرمستور إلى اليمين والكبد غادر الفصوص واحدة مباشرة فيالقسطرة الشريانية. </li><li style=";text-align:right;direction:rtl"> تسخين سائل الإرواء تهدف إلى درجة حرارة الكبد الهدف من 40 درجة مئوية. تبقي درجة الحرارة هذه في جميع أنحاء الارواء. </li><li style=";text-align:right;direction:rtl"> وضع مسبار التلألؤ على venovenous رئيس مضخة الالتفافية. </li><li style=";text-align:right;direction:rtl"> معايرة نظام رصد التسرب، عن طريق حقن جرعة صغيرة من 10 من mbq 99m TC-الزلال (1 مل) إلى الدوران الجهازي وتسجيل النشاط الأساسي. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> حقن عشرة أضعاف الجرعة أعلى، و 100 من mbq 99m TC-الزلال (1 مل)، في وحدة نضح الكبدية. </li><li style=";text-align:right;direction:rtl"> تسجيل أي تسرب من نظام نضح إلى الدوران الجهازي حيث أن زيادة النشاط تقاس التحقيق التلألؤ. </li><li style=";text-align:right;direction:rtl"> تسجيل أي تسرب من جهاز الدورة الدموية للنظام نضح عن زيادة في حجم في الخزان الوريدي. </li></ol></li><li style=";text-align:right;direction:rtl"> عندما يتم تأسيس دولة ثابتة لمعدل التدفق، أي تسرب موجود ولقد وصلت درجة حرارة الكبد 40 درجة مئوية، وضخ ملفلان بجرعة1 ملغم / كغم من وزن الجسم في النظام نضح مقسمة إلى جرعتين تعطى 30 دقيقة على حدة. </li></ol> 4. إنهاء الإرواء وإزالة القسطرة <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> بعد 60 دقيقة من نضح، تفريغ سائل الإرواء من النظام وري الكبد مع 1،000 مل من بلوراني. </li><li style=";text-align:right;direction:rtl"> إضافة وحدة واحدة من الكريات الحمراء معبأة إلى وحدة التروية، ولبث في الكبد ومن ثم وقف نضح. </li><li style=";text-align:right;direction:rtl"> الافراج عن المشبك Klintmalm ووقف النزف Rumel من الوريد الأجوف. </li><li style=";text-align:right;direction:rtl"> الافراج عن وقف النزف Rumel من الرباط الكبدي الإثناعشري. </li><li style=";text-align:right;direction:rtl"> إزالة ربطة من الشريان معدي. إزالة القسطرة وligate السفينة. </li><li style=";text-align:right;direction:rtl"> الافراج عن المشبك من الشريان الكبدي. </li><li style=";text-align:right;direction:rtl"> إزالة القسطرة من الوريد الغدد التناسلية وligate السفينة. </li><li style=";text-align:right;direction:rtl"> وقف-VENO الوريدي ضخ الالتفافية وقطع الأنابيب. </li><li style=";text-align:right;direction:rtl"> إغلاق البطن مع خياطة فافية دون انقطاع ومن ثم لخياطة الجلد داخل الجلد. </li><li style=";text-align:right;direction:rtl"> إزالة جatheters في عروق الوريد الفخذي والخارجية والضغط المحلي لمدة 5 دقائق. </li></ol> 5. بعد العملية الجراحية العناية <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> ينزع الأنبوب المريض ونقل إلى وحدة العناية بعد الجراحة لمدة 24 ساعة. حافظ على مراقبة الضغط الوريدي المركزي وضغط الدم الشرياني. </li><li style=";text-align:right;direction:rtl"> نقل المريض إلى قسم الجراحة لنموذجي من 3-7 أيام من الرعاية اللاحقة للعمليات الجراحية. </li><li style=";text-align:right;direction:rtl"> تواصل مع منخفضة الوزن الجزيئي هيبارين (LMWH) بجرعة من 5،000 IE / يوم أي ما مجموعه 4 أسابيع. </li></ol>

<ol>
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B., 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=Isolated+hepatic+perfusion+with+200+mg+melphalan+for+advanced+noncolorectal+liver+metastases.">Isolated hepatic perfusion with 200 mg melphalan for advanced noncolorectal liver metastases.</a> Annals of Surgical Oncology. 15 (7), 1891-1898 (2008).</li><li>Carvajal, R. D., 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=Effect+of+selumetinib+vs+chemotherapy+on+progression-free+survival+in+uveal+melanoma:+a+randomized+clinical+trial.">Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial.</a> JAMA : the Journal Of The American Medical Association. 311 (23), 2397-2405 (2014).</li><li>Sharma, K. V., 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=Hepatic+arterial+chemoembolization+for+management+of+metastatic+melanoma.">Hepatic arterial chemoembolization for management of metastatic melanoma.</a> AJR. American Journal Of Roentgenology. 190 (1), 99-104 (2008).</li><li>Eldredge-Hindy, 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=Yttrium-90+Microsphere+Brachytherapy+for+Liver+Metastases+From+Uveal+Melanoma:+Clinical+Outcomes+and+the+Predictive+Value+of+Fluorodeoxyglucose+Positron+Emission+Tomography.">Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography.</a> American Journal Of Clinical Oncology. , (2014).</li><li>Etten, B., 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=Isolated+hypoxic+hepatic+perfusion+with+orthograde+or+retrograde+flow+in+patients+with+irresectable+liver+metastases+using+percutaneous+balloon+catheter+techniques:+a+phase+I+and+II+study.">Isolated hypoxic hepatic perfusion with orthograde or retrograde flow in patients with irresectable liver metastases using percutaneous balloon catheter techniques: a phase I and II study.</a> Annals of Surgical Oncology. 11 (6), 598-605 (2004).</li><li>Ku, Y., 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=Extracorporeal+adriamycin-removal+following+hepatic+artery+infusion:+use+of+direct+hemoperfusion+combined+with+veno-venous+bypass.">Extracorporeal adriamycin-removal following hepatic artery infusion: use of direct hemoperfusion combined with veno-venous bypass.</a> Nihon Geka Gakkai Zasshi. 90 (10), 1758-1764 (1989).</li><li>Curley, S. A., 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=Hepatic+arterial+infusion+chemotherapy+with+complete+hepatic+venous+isolation+and+extracorporeal+chemofiltration:+a+feasibility+study+of+a+novel+system.">Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system.</a> Anti-Cancer Drugs. 2 (2), 175-183 (1991).</li><li>Beheshti, M. V., 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+isolated+liver+perfusion+for+treatment+of+hepatic+malignancy:+preliminary+report.">Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report.</a> Journal of Vascular And Interventional Radiology : JVIR. 3 (3), 453-458 (1992).</li></ol>

The authors have nothing to disclose.

المرضى الذين يعانون من سرطان الجلد المنتشر العنبي يكون عدد قليل من الخيارات العلاجية. والعلاج الكيميائي 6، العلاج المناعي 23 و العلاج المستهدف 24 لم تكن قادرة على أن تظهر تحسن OS. للمرضى الذين يعانون القليلة الانبثاث الكبد، استئصال الكبد هو خيار 12.</s...

سرطان الجلد العنبي هو الورم الخبيث العين الأساسي الأكثر شيوعا في البالغين، مع نسبة لها تكون أعلى نسبة في السكان قوقازي 1. يتكون العلاج المحلية من استئصال أو البلاك المحلية العلاج الإشعاعي 2،3. بغض النظر عن العلاج المحلية، والمرض المنتشر تتطور في نهاية المطاف في حوالي 35-50٪ من المرضى 4،5. الكبد هو الموقع الأكثر شيوعا لالانبثاث وحوالي 50٪ من المرضى الحالي مع الانبثاث الكبد معزولة. ومتوسط ​​البقاء الإجمالي (OS) للمرضى الذين يعانون من الانبثاث الكبد هو 6-12 4 أشهر. تم استكشاف العديد من الاستراتيجيات المختلفة العلاج الشامل والإقليمية، ولكن معدلات البقاء على قيد الحياة لم تتحسن 2. العلاج مع العلاج الكيميائي النظامية، وكلاهما مادة واحدة (داكاربازين أو Temozolomide 6) أو مزيج من العلاجات (نظام بولد 7، جيمسيتابين مع treosulfan 8)، ويظهر معدلات الاستجابة أقل ثم10٪. وقد أظهرت الكبدي العلاج الكيميائي داخل الشريان (HIA) معدل أعلى قليلا العام استجابة للعلاج الكيميائي مقارنة النظامية، ولكن أي زيادة في بقاء الكلي 9. أظهر chemoembolization Transarterial (TACE) مع سيسبلاتين وكاربوبلاتين استجابة جزئية في 57٪ من المرضى الذين يعانون من البقاء على قيد الحياة وسيطة من 9 أشهر 10. وقد أظهرت العلاج الإشعاعي الداخلي الانتقائي (SIRT) استجابة جزئية في 62٪ من المرضى الذين يعانون من البقاء على قيد الحياة وسيطة من 7 أشهر 11. في دراسة عن استئصال الكبد، بما في ذلك 255 مريضا، تم التبليغ عن البقاء الإجمالي 14 شهرا. في 76 من المرضى حيث كان الاستئصال الكامل مجهريا ممكن، وبقاء 27 شهرا 12. نضح الكبدي معزولة (IHP) هو خيار العلاج الإقليمي، وضعت أصلا من قبل ريان وAusman. الأساس المنطقي وراء هذه التقنية هو عزل جراحيا ويروي الكبد مع جرعة عالية من العلاج الكيميائي وكيل مع تجنب النظامية لxicity 13. وبالإضافة إلى ذلك، ارتفاع الحرارة المتزامنة يتوسط لامتصاص زيادة من وكيل العلاج الكيميائي بسبب التغيرات في تدفق الدم وورم نفاذية الغشاء الخلوي 14. ويؤكد كاملة العزلة الأوعية الدموية مع تقنية التتبع المشعة باستخدام TC-99 وصفت المصل البشري الزلال 15. وقد أظهرت دراسة استعادية المرحلة الثانية فائدة البقاء على قيد الحياة المحتملة من 14 شهرا (26 مقابل 12 شهرا) للمرضى التي خضعت IHP مقارنة أطول الناجين مع الانبثاث الكبد سرطان الجلد عنبي في السويد 16. هنا نقدم تقنية IHP مع لمحة موجزة عن النتائج الحالية والآفاق المستقبلية.

<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

نضح الكبدي معزولة (IHP) هو الإجراء حيث يتم عزل الكبد جراحيا ومع perfused على نسبة عالية من وكيل ملفلان العلاج الكيميائي. لفترة وجيزة، يبدأ الإجراء مع الإعداد لتجاوز-VENO الوريدي عن طريق الجلد من الوريد الفخذي إلى الوريد الوداجي الخارجي. عن طريق فتح البطن، ثم يتم إدخال القسطرة في الشريان الكبدي السليم والوريد الأجوف. الوريد البابي والوريد الأجوف، سواء supra- وinfrahepatically، وفرضت ذلك الحين. يتم توصيل الشرايين والقسطرة الوريدية إلى جهاز القلب الرئة والكبد perfused لمع ملفلان (1 ملغ / كغ من وزن الجسم) لمدة 60 دقيقة. بهذه الطريقة فمن الممكن أن يروي محليا الكبد مع جرعة عالية من العلاج الكيميائي وكيل، دون تسرب إلى الدوران الجهازي. في الدراسات السابقة بما في ذلك المرضى الذين يعانون من الانبثاث الكبد معزولة من سرطان الجلد العنبية، وهو معدل الاستجابة الكلي من 33-100٪ ومتوسط ​​بقاء ما بين 9 و 13 شهرا،تم الإبلاغ. والهدف من هذا البروتوكول هو إعطاء وصف واضح لكيفية تنفيذ الإجراء ومناقشة IHP كخيار لعلاج الكبد الانبثاث من سرطان الجلد العنبي.

وتضمن تقرير أولي 22 مريضا عولجوا ملفلان مع أو بدون TNF-ألفا. أظهرت النتائج معدل الاستجابة الكلي 62٪، من بينهم اثنان من المرضى الذين يعانون من CR (10٪)، ومتوسط ​​البقاء الإجمالي 11 شهرا 20. وأفادت دراسة لاحقة على نتائج 29 مريضا على التوالي تعامل باستخدام ملفلان وحدها. وك?...

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.

معزولة كبدي الإرواء كعلاج للالانبثاث الكبد من العنبية الميلانوما

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

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13.3K Views.  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.

Video: 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.

العمليات الجراحية لنموذج الفئران من الجزئي زرع الكبد orthotopic مع إعادة الإعمار الكبدي الشرياني

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

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.

وما قبل السريرية الفئران نموذج من الانبثاث الكبدي

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.

التصوير بالرنين المغناطيسي موجهة dmPFC-rTMS كعلاج للمقاومة للعلاج اضطراب اكتئابي

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.

عن طريق الجلد كبدي الإرواء (PHP) مع ملفلان كعلاج للالغير قطوعة الانبثاث تقتصر على الكبد

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.

جيل من كبد الفأر أنسنة طريق كبد الإنسان خلايا الجذعية

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.

طريقة التسليم المباشر القطاعي البينية الكبد باستخدام نموذج الفأر الكبد نقيري المشبك

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.

علاج الأورام الثانوية في الكبد جراء استخدام أسلوب وحدة تخزين هدف داخلي للعلاج بالمناظير باستخدام الأشعة الجسم الأشعة

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.

نموذج حيوانات صغيرة من نضح الكبد نورموثيرميك السابقين فيفو

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.

قياس التدرج الضغط الوريدي الكبدي وخزعة الكبد عبرة

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.

المورين الدقة قطع شرائح الكبد كنموذج السابق فيفو بيولوجيا الكبد

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