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

환자 동의서를 작성 제공하고, 연구는 예테보리 대학에서 지역 윤리 심의위원회에 의해 승인되었다. 1. 마취 <ol><li> 모든 모니터링 (ECG, 혈압 커프) (17)을 설정합니다. </li><li> 중반 흉부 레벨 17 아래에서 경막 외 카테터를 삽입합니다. </li><li> 포폴 2 ㎎ / ㎏, 펜타닐 150 μg의, 그리고 Rocuronium 0.6 mg의 마취를 유도 / 이전에 삽입 말초 정맥 카테터를 통해 킬로그램. </li><li> Preoxygenate하고 삽관 환자. 세보, 산소 및 공기 (17)와 마취를 유지한다. </li><li> 더블 루멘 중심 정맥 카테터 및 동맥 카테터를 삽입합니다. CVP와 동맥압 (17)를 모니터링합니다. </li></ol> 선박의 간 및 캐 뉼러 2. 분리 <ol><li> 헤파린의 100 IE / kg을 관리하고 예방 적 항생제를 (줄 예를 들어, 트리 메소 프림 80의 160 mg의설파 0 mg)을 얻었다. </li><li> 경피적 Seldinger 기술을 사용하여, 대퇴 정맥에 17 프랑 카테터와 외부 경정맥 (18)에 15 프랑 카테터를 배치합니다. 투시하여 카테터의 위치를​​ 확인합니다. </li><li> 중간 선 아래로 칼 모양의 과정에서 L 자형 절개하여 개복술을 수행 한 후 오른쪽 subcostal 절개 19 일까지 연장. </li><li> 더 간외 전이가 완벽한 검사 및 촉진하여 복부에 없는지 확인합니다. <ol><li> 의심스러운 병변이 발견되면 동결 절편에 의해 악성 종양을 확인합니다. </li><li> 간외 현시 (​​periaortal 병증, 복부 전이)의 증거가있는 경우의 절차를 종료한다. 간 문부에서 림프절 종대는 금기로 간주되지 않습니다. </li></ol></li><li> 낫 인대, 좌우의 삼각 인대 및 관상 인대 (19)를 분할하여 간을 동원. </li><li> caval을 해부하다복막 지류 혈관의 결찰과 다이어프램까지 신장 정맥에서 시작 정맥. </li><li> 오른쪽 부신 정맥을 확인하고 주위 혈관 루프를 배치합니다. </li><li> 오른쪽 성선 정맥을 확인합니다. 5~10cm을 위해 그것을 해부. caval 정맥의 입구 주위에 지갑 문자열 봉합을 놓습니다. <ol><li> 성선 정맥에 원심 합자를 놓습니다. 가위를 사용하여 caval 정맥에서 성선 정맥 3-5cm를 엽니 다. </li><li> 오른쪽 성선 정맥을 통해 18 천을 와이어 강화 카테터를 삽입하고 retrohepatically 신장 정맥 위의 팁을 배치합니다. </li><li> 카테터의 위치를​​ 확보하기 위해 성선 정맥 주위에 합자를 놓습니다. </li><li> 카테터를 통해 혈액의 반환을 확인합니다. 카테터 (18) Heparinize. </li></ol></li><li> hepatoduodenal 인대를 해부하고, 간동맥, 위 십이지장 동맥 적절한 간동맥을 시각화. <ol><li> 장소 용기는 일반적인 간 줄게 주위에 루프공예 및 gastrodoudenal 동맥. </li><li> 포털 정맥을 해부하고 주위 혈관 루프를 배치합니다. </li><li> 담관 함유 인대의 나머지 부분을 분리하고 용기 루프에서이 모두 포함된다. </li></ol></li><li> 선박 루프 위 십이지장 동맥을 들어 올립니다. 동맥 유입을 중단 한 후, 가위를 사용하여 절개를합니다. <ol><li> 적절한 간동맥에 자사의 팁 8-12 프랑 카테터를 삽입합니다. 위 십이지장 동맥 주위에 합자와 위치를 고정합니다. </li><li> 카테터 혈액 반환을 확인하고 그것을 18 다음을 heparinize. </li></ol></li><li> 프라임 적혈구 포장 한 단위, 알부민의 100 ㎖ (50g / L), Tribonat (중탄산 나트륨), 헤파린 2500 단위 (5000 IE / ㎖) 100㎖로 정출 물 250ml를 관류 시스템. </li><li> 동맥 및 롤러 펌프를 구비 심폐 기계 이루어진 관류 시스템 caval 정맥 카테터 및 히터를 연결 t일회용 타입의 혈조, 산화 기 및 배관 시스템과 ogether. </li><li> 히터 유닛과 함께, 원심 펌프로 구성된 정 정맥 바이 패스 펌프 대퇴 및 외부 경정맥 카테터를 연결하고 우회를 시작합니다. </li><li> infrahepatically 신장 정맥 위의 caval 정맥 주위에 Rumel 지혈대를 강화하고 Klintmalm 혈관 클램프를 사용하여 suprahepatically caval 정맥을 체결하여 간의 분리를 완료합니다. <ol><li> 담관, 포털 정맥과 오른쪽 부신 정맥 주위에 Rumel 지혈대를 조이고 마지막으로 혈관 클램프를 사용하여 간동맥을 클램프. </li></ol></li></ol> 3. 관류 <ol><li> 관류를 시작하고 수동으로 혈조의 혈중 농도를 모니터링 할 수 있습니다. 정상 상태 레벨이 500-1,200 ㎖ / 분 사이, 보통의 유량에 도달 할 때까지 유량을 조정한다. </li><li> 오른쪽과 왼쪽 간 엽에 서미스터 프로브를 직접 하나에동맥 카테터. </li><li> C. O 40의 타겟 간 온도를 목표 관류 히트 관류에 걸쳐이 온도를 유지합니다. </li><li> 정 정맥 바이 패스 펌프 머리에 섬광 프로브를 놓습니다. </li><li> 전신 순환으로 10 MBq 내지 99m의 TC-알부민 (1 mL)을 작은 도즈를 주입함으로써, 누설 모니터링 시스템을 보정하고 기준 활성을 등록한다. <ol><li> 간 관류 장치로, 10 배 높은 용량, 100 MBq의의 99m TC-알부민 (1 ml)에 주입한다. </li><li> 섬광 프로브로 측정 활동의 증가로 전신 순환에 관류 시스템에서 누출을 기록합니다. </li><li> 혈조에 볼륨의 증가로 관류 시스템에 전신 순환의 누출을 기록합니다. </li></ol></li><li> 유량의 정상 상태가 확립 될 때의 용량을 주입 멜 팔란, 누설이 존재하지 않으며 간 온도는 40 ° C에 도달관류 시스템에 1 ㎎ / kg (체중) 떨어져 30 분 투여 량으로 주어진 두 나누었다. </li></ol> 4. 관류을 종료하고 카테터를 제거 <ol><li> 관류의 60 분 후, 시스템으로부터 관류를 비우고 정질 1,000 ml로 간 관개. </li><li> 관류 장치에 포장 적혈구의 한 단위를 추가, 간으로 주입 한 후 관류를 중지합니다. </li><li> Klintmalm 클램프 및 caval 정맥에서 Rumel 지혈대를 놓습니다. </li><li> hepatoduodenal 인대에서 Rumel 지혈대를 놓습니다. </li><li> 위 십이지장 동맥에서 합자를 제거합니다. 카테터를 제거하고 혈관을 결찰. </li><li> 간동맥에서 클램프를 놓습니다. </li><li> 성선 정맥 카테터를 제거하고 혈관을 결찰. </li><li> veno 정맥 바이 패스 펌프를 중지하고 튜브를 분리합니다. </li><li> 중단 근막 봉합 한 후 피내 피부 봉합과 복부를 닫습니다. </li><li> C를 제거대퇴 및 외부 경정맥에 atheters과 5 분 동안 현지 압력을 적용합니다. </li></ol> 5. 수술 후 케어 <ol><li> 환자가 튜브를 빼내 24 시간 동안 수술 후 관리 장치에 전송할 수 있습니다. 중심 정맥 압력과 동맥 혈압을 모니터링하십시오. </li><li> 수술 후 치료 3-7 일 일반에 대한 수술 부서에 환자를 전송합니다. </li><li> 4 주 총 5000 IE / 일의 투여 량에서 저 분자량 헤파린 (LMWH) 계속. </li></ol>

<ol>
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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.

전이성 포도막 흑색 종 환자는 몇 치료 옵션이 있습니다. 화학 요법 (6), 면역 요법 (23)과 표적 치료 (24)는 개선 된 OS를 보여줄 수 없었다. 약간의 간 전이 환자, 간 절제술은 옵션 (12)이다. 다른 치료는 간 동맥 화학 요법 (HIA) 9, 화학 색전술 (TACE) (25)와 선택적 내부 방사선 치료 (SIRT) (26)를 포함한다. IHP는 주요 복잡한 수...

포도막 흑색 종 발병률은 백인 인구 1에서 가장 높은 인으로, 성인에서 가장 흔한 일차 인공 악성 종양이다. 지역 치료는 안구 적출술 또는 지방 플라크 방사선 치료 2,3로 구성되어 있습니다. 에 관계없이 지역 치료, 전이성 질환은 궁극적으로 환자 4,5의 약 35~50%을 개발할 것입니다. 간은 가장 일반적인 전이 부위와 격리 간전에 존재 환자의 약 50 %이다. 간 전이 환자의 전체 생존 기간의 중앙값 (OS)는 6-12개월 4입니다. 여러 다른 지역 및 전신 치료 전략이 모색되었지만 생존율이 향상되지 않았다. 전신 항암 화학 요법 치료, 모두 단일 물질 (다카 바진 또는 테모 졸로 마이드 6) 또는 조합 치료 (BOLD식이 요법 7, treosulfan 8 젬시 타빈)를 선택한 다음, 이하의 응답 속도를 보여줍니다10 %. 간 동맥 화학 요법 (HIA)는 전신 화학 요법에 비해 약간 높은 반응률하지만, 전체 생존 기간 (9)의 증가없이 보여 주었다. 시스플라틴 (cisplatin) 및 카보 플 라틴 (carboplatin)과 화학 색전술 (TACE)는 9개월 (10)의 중앙 생존 환자의 57 %에서 부분 반응을 보였다. 선택적 내부 방사선 치료 (SIRT)는 7개월 (11)의 중앙 생존 환자의 62 %에서 부분 반응을 보이고있다. 255 명의 환자를 포함하는 간 절제술에 대한 연구에서 14 개월 생존율이보고되었다; 현미경 적 완전 절제가 가능했던 환자의 76, 생존 27개월 (12)이었다. 고립 간 관류 (IHP)는 원래 라이언 Ausman에 의해 개발 된 지역 치료 방법이다. 뒤에 기술의 이론적 근거는 전신적으로 회피하면서 수술 분리 및 화학 요법 제의 투여 량과 높은 간을 관류하는xicity (13). 또한, 동시 고열 종양 혈류 세포막 투과성 (14)의 변화에 의해 화학 요법 제의 증가 된 흡수를 매개한다. 완전한 혈관 아이솔레이션 TC-99은 인간 혈청 알부민 (15)를 이용하여 표지 된 방사성 트레이서 기법으로 확인된다. 후 향적 단계 II 연구는 스웨덴 16 포도막 흑색 종 간 전이 가장 긴 생존자에 비해 IHP을 시행 한 환자 14 개월 (26 대 12개월)의 잠재적 인 생존 이득을 보여 주었다. 여기에서 우리는 현재의 결과와 향후 전망에 대한 간단한 리뷰와 함께 IHP의 기술을 제시한다.

<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

관류 간 격리 (IHP)는 간이 수술 단리 화학 요법 제의 멜 팔란 고농도 관류 절차이다. 간단히, 절차는 외부 경정맥에 대퇴 정맥에서 경피적 veno 정맥 바이 패스의 설치를 시작합니다. 개복술을 통해, 카테터는 적절한 간동맥 및 caval 정맥에 삽입됩니다. 위의의 뜻과 infrahepatically, 다음 클램핑 모두 문맥과 caval 정맥. 동맥과 정맥 카테터 심폐 기계에 연결되어 간 60 분 동안 멜 팔란 (1 ㎎ / kg 체중)로 관류시켰다. 그것이 가능하다이 방법은 로컬 전신 순환으로 누출하지 않고, 화학 요법 제의 투여 량과 높은 간 관류. 포도막 흑색 종의 고립 간 전이 환자를 포함하여 이전의 연구에서, 33-100%의 전반적인 응답 속도와 9 13개월 사이의 평균 생존 기간,보고되고있다. 이 프로토콜의 목적은 절차를 수행하는 방법의 명확한 설명을 제공하고, 포도막 흑색 종의 간전 대한 치료 옵션으로 IHP을 논의한다.

초기 보고서 또는 TNF-α없이 멜 팔란 치료 22 명을 포함. 결과는 두 CR (10 %)을 가진 환자, 11 개월 (20)의 중앙값을 포함 생존율 62 %의 반응율을 보였다. 후속 연구는 혼자 멜 팔란를 사용하여 치료 29 명의 환자의 결과를보고했다. 결과는 10 % 완전 반응 12 개월 (21)의 중앙 생존 기간을 포함하여 62 % 전체 응답과 매우 유사했다. 로 Rizell 등. 연구에서, 포도막 ?...

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.

포도막 흑색 종의 간전이에 대한 치료로 고립 간 관류

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

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13.3K 조회수.  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.

비디오: 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.

간 간선 재건과 부분 Orthotopic 간 이식의 쥐 모델에 대한 외과 절차

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

연구

의학

Osteopathic Manipulative Treatment as a Useful Adjunctive Tool for Pneumonia

Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 20071 and resulted in the hospitalization of 1.1 million patients2. With an average length of in-patient hospital stay of five days2, pneumonia and influenza comprise significant financial burden costing the United States $40.2 billion in 20053. Under the current Infectious Disease Society of America/American Thoracic Society guidelines, standard-of-care recommendations include the rapid administration of an appropriate antibiotic regiment, fluid replacement, and ventilation (if necessary). Non-standard therapies include the use of corticosteroids and statins; however, these therapies lack conclusive supporting evidence4. (Figure 1)

Osteopathic Manipulative Treatment (OMT) is a cost-effective adjunctive treatment of pneumonia that has been shown to reduce patients&#8217; length of hospital stay, duration of intravenous antibiotics, and incidence of respiratory failure or death when compared to subjects who received conventional care alone5. The use of manual manipulation techniques for pneumonia was first recorded as early as the Spanish influenza pandemic of 1918, when patients treated with standard medical care had an estimated mortality rate of 33%, compared to a 10% mortality rate in patients treated by osteopathic physicians6. When applied to the management of pneumonia, manual manipulation techniques bolster lymphatic flow, respiratory function, and immunological defense by targeting anatomical structures involved in the these systems7,8, 9, 10.

The objective of this review video-article is three-fold: a) summarize the findings of randomized controlled studies on the efficacy of OMT in adult patients with diagnosed pneumonia, b) demonstrate established protocols utilized by osteopathic physicians treating pneumonia, c) elucidate the physiological mechanisms behind manual manipulation of the respiratory and lymphatic systems. Specifically, we will discuss and demonstrate four routine techniques that address autonomics, lymph drainage, and rib cage mobility: 1) Rib Raising, 2) Thoracic Pump, 3) Doming of the Thoracic Diaphragm, and 4) Muscle Energy for Rib 1.5,11

Pneumonia is one of the top ten leading causes of death in the U.S. Osteopathic manipulative techniques (OMT) may be utilized as an adjunctive therapy in the treatment of pneumonia to enhance biomechanical and immune function; and ultimately, to reduce hospital stay, duration of antibiotics, incidence of respiratory failure, and mortality. In this video-article, we will review randomized controlled studies on the use of OMT in pneumonia patients, as well as demonstrate specific hands-on techniques that are routinely practiced by osteopathic physicians when treating pulmonary infections.

Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 20071 and resulted in ...

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.

간 전이의 전임상 쥐과 모델

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.

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.

간으로 밀폐 절제 불가능한 전이에 대한 치료로 멜 팔란과 경피적 간 관류 (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.

인간 간 줄기 세포를 이용한 인간형 마우스 간 세대

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.

쥐 간 문부 클램프 모델을 사용하여 직접 분절 인트라 간 납품 방법

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.

몸 정위 적 방사선 치료에 대 한 내부 대상 볼륨 메서드를 사용 하 여 간 전이의 치료

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 Normothermic 간 관류의 작은 동물 모델

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

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.

뮤린 정밀 절단 간 슬라이스 간 생물학의 Ex Vivo 모델로

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