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

Pacientes desde consentimento informado eo estudo foi aprovado pelo Conselho de Revisão de Ética Regional da Universidade de Gotemburgo. 1. Anestesia <ol><li> Configurar todo o acompanhamento (ECG, manguito de pressão arterial) 17. </li><li> Insira um cateter peridural no baixo e médio nível torácico 17. </li><li> Induzir a anestesia com propofol 2 mg / kg, 150 mcg de fentanil e Rocuronium 0,6 mg / kg através de um cateter venoso periférico inserido anteriormente. </li><li> Preoxygenate e entubar o paciente. Manter a anestesia com sevoflurano, oxigênio e ar 17. </li><li> Insira um cateter venoso central duplo lúmen e um cateter arterial. Monitorar CVP e pressão arterial 17. </li></ol> 2. Isolamento do Fígado e canulação da Vessels <ol><li> Administrar 100 IE / kg de heparina e dar a profilaxia com antibióticos (por exemplo, 160 mg de trimetoprim e 800 mg de sulfametoxazol). </li><li> Usando a técnica de Seldinger percutânea, coloque um 17 Fr cateter na veia femoral e a 15 Fr cateter na veia jugular externa 18. Verificar as posições dos cateteres por fluoroscopia. </li><li> Realize uma laparotomia por uma incisão em forma de L do apêndice xifóide abaixo da linha média e depois estendido para uma incisão subcostal direita 19. </li><li> Verifique se não há metástases extra-hepática existem no abdômen por uma inspeção completa e palpação. <ol><li> Se quaisquer lesões suspeitas são encontrados, verificar malignidade por congelação. </li><li> Encerrar o processo se houver provas de manifestação extra-hepática (adenopathy periaortal, metástases abdominais). Linfadenopatia no porta hepática não é considerada uma contra-indicação. </li></ol></li><li> Mobilizar o fígado através da divisão do ligamento falciforme, o ligamento triangular esquerda e direita e do ligamento coronário 19. </li><li> Dissecar a cavaveia começando a partir das veias renais até o diafragma com ligadura de veias tributárias retroperitônio. </li><li> Identifique a veia adrenal direita e coloque um laço navio em torno dele. </li><li> Identifique a veia gonadal direita. Dissecá-lo por 5-10 cm. Coloque uma sutura em bolsa em torno da entrada da veia cava. <ol><li> Coloque uma ligadura distal na veia gonadal. Com uma tesoura, abra a veia gonadal 3-5 cm a partir da veia cava. </li><li> Insira um 18 Fr cateter reforçado com fio através da veia gonadal direita e coloque a ponta retrohepatically acima das veias renais. </li><li> Colocar uma ligadura em torno da veia gonadal para fixar a posição do cateter. </li><li> Verificar o retorno do sangue através do cateter. Heparinização do cateter 18. </li></ol></li><li> Dissecar o ligamento hepatoduodenal e visualizar a artéria hepática comum, a artéria gastroduodenal e da artéria hepática própria. <ol><li> Lugar embarcação laços em torno da arte hepático comumry e a artéria gastrodoudenal. </li><li> Dissecar a veia portal e colocar um laço em torno dele navio. </li><li> Isolar o resto do ligamento contendo o ducto biliar comum e incluem tudo isto num ciclo navio. </li></ol></li><li> Levante a artéria gastroduodenal com o ciclo de navio. Depois de interromper o fluxo arterial, fazer uma incisão com uma tesoura. <ol><li> Insira um 8-12 Fr cateter com a ponta para dentro da artéria hepática própria. Fixe a posição com uma ligadura em torno da artéria gastroduodenal. </li><li> Verifique o retorno do sangue no cateter e depois heparinizar ele 18. </li></ol></li><li> Primeiro o sistema de perfusão com uma unidade de eritrócitos, 100 ml de albumina (50 g / L), 100 ml de Tribonat (bicarbonato de sódio), 2500 unidades de heparina (5.000 IE / ml) e 250 ml de cristalóides. </li><li> Ligue o arterial e os cateteres da veia cava para o sistema de perfusão que consiste de uma máquina coração pulmão equipado com uma bomba de cilindro e um aquecedor together com um reservatório, oxigenador e tubos venosos sistemas do tipo descartável. </li><li> Ligar os cateteres jugulares externas femorais e para a bomba de bypass veno consiste de uma bomba centrífuga, juntamente com uma unidade de aquecimento e iniciar desvio. </li><li> Complete o isolamento do fígado, apertando um torniquete Rumel em torno da veia cava infrahepatically acima das veias renais e fixação da veia cava suprahepatically usando uma pinça vascular Klintmalm. <ol><li> Aperte um torniquete Rumel em torno do ducto biliar comum, a veia porta ea veia adrenal direita e finalmente prender a artéria hepática usando uma pinça vascular. </li></ol></li></ol> 3. A perfusão <ol><li> Iniciar a perfusão e monitorizar o nível de sangue manualmente no reservatório venoso. Ajustar o caudal até um nível de estado estacionário é atingido, geralmente uma taxa de fluxo entre 500-1,200 ml / min. </li><li> Coloque sondas thermistor em lobos direito e esquerdo do fígado e outro diretamentedo cateter arterial. </li><li> Aqueça o perfusato visando a uma temperatura de fígado meta de 40 o C. Manter esta temperatura em toda a perfusão. </li><li> Coloque uma sonda cintilação sobre a cabeça da bomba de bypass venovenoso. </li><li> Calibrar o sistema de controlo de fugas, por injecção de uma pequena dose de 10 MBq de 99m Tc-albumina (1 ml) para a circulação sistémica e registar a actividade da linha de base. <ol><li> Injectar uma dose de dez vezes superior, com 100 MBq de 99m Tc-albumina (1 ml), para a unidade de perfusão hepática. </li><li> Grave qualquer fuga do sistema de perfusão para a circulação sistémica como um aumento na actividade medida pela sonda de cintilação. </li><li> Grave qualquer fuga a partir da circulação sistémica para o sistema de perfusão como um aumento no volume no reservatório venoso. </li></ol></li><li> Quando em estado de equilíbrio da taxa de fluxo é estabelecido, qualquer fuga está presente e a temperatura fígado atingiu 40 ° C, injectar o melfalano, a uma dose de1 mg / kg de peso corporal para o sistema de perfusão dividida em duas doses, administradas de 30 min. </li></ol> 4. Acabar com a perfusão e remoção dos cateteres <ol><li> Após 60 min de perfusão, esvaziar o perfusato do sistema e irrigar o fígado, com 1.000 ml de cristalóide. </li><li> Adicionar uma unidade de eritrócitos para a unidade de perfusão, infundir no fígado e, em seguida, parar a perfusão. </li><li> Solte a braçadeira Klintmalm e do torniquete Rumel da veia cava. </li><li> Solte o torniquete Rumel do ligamento hepatoduodenal. </li><li> Remover a ligadura da artéria gastroduodenal. Remover o cateter e ligar o vaso. </li><li> Solte o grampo da artéria hepática. </li><li> Remover o cateter da veia gonadal e ligar o vaso. </li><li> Pare a bomba de desvio veno-venosa e desconectar os tubos. </li><li> Feche o abdômen com uma sutura fascial ininterrupta e, em seguida, uma sutura intradérmica da pele. </li><li> Remover o catheters nas veias jugulares femorais e externos e aplicar pressão local para 5 min. </li></ol> 5. Cuidados Pós-Operatórios <ol><li> Extubação do paciente e transferência para unidade de cuidados pós-operatórios, durante 24 horas. Manter o monitoramento da pressão venosa central e pressão arterial. </li><li> Transferir o paciente a um serviço de cirurgia para um típico de 3-7 dias de cuidados pós-operatórios. </li><li> Continuar com a heparina de baixo peso molecular (HBPM) a uma dose de 5.000 IE / dia para um total de 4 semanas. </li></ol>

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The authors have nothing to disclose.

Pacientes com melanoma uveal metastático têm poucas opções terapêuticas. Quimioterapia 6, a imunoterapia 23 e terapia-alvo 24 não ter sido capaz de mostrar um melhor OS. Para pacientes com poucas metástases hepáticas, ressecção hepática é uma opção 12. Outros tratamentos incluem quimioterapia hepática intra-arterial (HIA) 9, quimioembolização transarterial (TACE) 25 e terapia seletivo interno radiação (SIRT) 26. IHP é uma intervenção cirúrgica importante e complexo e, desde o primeiro relatório do Ausman tem havido muitos desenvolvimentos da técnica cirúrgica. Em 2004, van Etten e colegas relataram que os primeiros resultados clínicos usando a perfusão hepática hipóxico isolado (IHHP) técnica 27. No início de 1990, três grupos independentes desenvolveu um sistema de perfusão hepática percutânea romance (PHP) usando chemofiltration extracorpórea 28-30. Não há estudosComparando estas técnicas para IHP foram realizados. Os relatórios até agora não parecem ser a favor de uma técnica específica. A seleção dos pacientes é de grande importância para este tratamento. Uma vez que é um local de tratamento, não deve haver evidência de doença extra-hepática. Devido ao risco de desenvolvimento de insuficiência hepática, não mais do que 50% do volume do fígado deveria ser substituído pelo tumor 22. Os doentes devem ter uma boa performance status (ECOG 0-1) e não coração-, lung-, de rim ou doença do fígado que pode aumentar o risco de morbidade grave após a cirurgia. Em um recente ensaio clínico de fase II do nosso grupo, a sobrevida média de 26 meses foi mostrado, o que implica um benefício de sobrevivência potencial de 14 meses, em comparação com um grupo controle de 16. Para verificar esse achado, um ensaio multicêntrico, randomizado de fase III entre IHP e Melhor Cuidados Alternativos (BAC) iniciou recentemente na Escandinávia (trial do SCANDIUM, número ClinicalTrials: NCT01.785.316). O tratamento BAC pode abranger todas as outras opções de tratamento, em curso ou experimentais, com a noção de que cross-over não é permitida a partir do BAC para grupo IHP. Os critérios de inclusão incluem biópsia verificada metástases hepáticas e nenhuma evidência de manifestações extra-hepáticas de tumores por PET-CT. O objectivo primário é a sobrevida global em 24 meses, com endpoints secundários, incluindo taxa de resposta, sobrevivência livre de progressão e qualidade de vida. A integração, prevista é de 78 pacientes durante 5 anos. Em resumo, ainda não existe um tratamento que, em ensaios de fase III demonstrou qualquer sobrevida global prolongada para pacientes com metástases hepáticas melanoma da úvea. IHP é uma terapia regionais interessante e promissor, onde potenciais benefícios na sobrevivência estão sendo investigados em um estudo randomizado (experimentação de SCANDIUM).

Melanoma da úvea é o tumor maligno intra-ocular mais comum em adultos, com a incidência ser maior em populações caucasianas 1. O tratamento local consiste de enucleação ou placa local radioterapia 2,3. Independentemente do tratamento local, doença metastática acabará por se desenvolver em cerca de 35-50% dos pacientes 4,5. O fígado é o sítio mais comum de metástases e aproximadamente 50% dos pacientes apresentam-se com metástases do fígado isoladas. A sobrevida global mediana (OS) para pacientes com metástases hepáticas é 6-12 meses 4. Várias estratégias de tratamento sistêmicos e regionais diferentes foram exploradas, mas as taxas de sobrevivência não melhoraram 2. O tratamento com quimioterapia sistêmica, tanto substância única (dacarbazina ou temozolomida 6) ou tratamentos combinados (regime BOLD 7, gemcitabina com treosulfan 8), mostra taxas de resposta de menos de10%. Quimioterapia intra-arterial hepática (HIA) mostrou uma taxa ligeiramente superior global de resposta em comparação com a quimioterapia sistêmica, mas nenhum aumento na sobrevida global 9. Quimioembolização transarterial (TACE) com cisplatina e carboplatina mostrou uma resposta parcial em 57% dos pacientes com uma sobrevida média de 9 meses 10. Terapia de radiação interna seletiva (SIRT) mostrou uma resposta parcial em 62% dos pacientes com uma sobrevida média de 7 meses 11. Em um estudo sobre a ressecção hepática, incluindo 255 pacientes, uma sobrevida global de 14 meses foi relatado; em 76 dos pacientes, onde a ressecção completa microscopicamente foi possível, a sobrevivência foi de 27 meses 12. Perfusão hepática isolada (IHP) é uma opção de tratamento regional, originalmente desenvolvido por Ryan e Ausman. A lógica por trás da técnica é isolar cirurgicamente e aspergir o fígado com uma alta dose de um agente quimioterapêutico, evitando sistêmica paraxicity 13. Além disso, a hipertermia concomitante medeia um aumento da absorção do agente quimioterapêutico por alterações no fluxo de sangue do tumor e a permeabilidade da membrana celular 14. Isolamento vascular completo é confirmado com uma técnica marcador radioativo usando Tc-99 marcado albumina sérica humana 15. Um estudo retrospectivo de fase II mostrou um benefício potencial de sobrevivência de 14 meses (26 x 12 meses) para os pacientes que foram submetidos a IHP em comparação com os sobreviventes mais longas com metástases hepáticas melanoma uveal na Suécia 16. Aqui apresentamos a técnica de IHP com uma breve avaliação dos resultados atuais e perspectivas futuras.

<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

Perfusão hepática Isolado (IHP) é um procedimento em que o fígado é cirurgicamente isolado e perfundido com uma elevada concentração do melfalano agente quimioterapêutico. Resumidamente, o processo inicia-se com a configuração de um desvio veno-venosa percutânea a partir da veia femoral para a veia jugular externa. Através de uma laparotomia, cateteres são então inserido na artéria hepática adequada e a veia cava. A veia porta ea veia cava, tanto supra e infrahepatically, são então presos. O cateteres arteriais e venosas são ligados a uma máquina coração pulmão e do fígado é submetido a perfusão com o melfalano (1 mg / kg de peso corporal) durante 60 min. Desta forma, é possível perfundir localmente o fígado com uma dose elevada de um agente quimioterapêutico, sem fugas, para a circulação sistémica. Em estudos anteriores, incluindo pacientes com metástases hepáticas isoladas de melanoma da úvea, uma taxa de resposta de 33-100% e uma sobrevida média entre 9 e 13 meses,têm sido relatados. O objectivo deste protocolo é para dar uma descrição clara de como realizar o procedimento e para discutir IHP como uma opção de tratamento para metástases hepáticas de melanoma uveal.

Um relatório inicial incluiu 22 pacientes tratados com melfalano com ou sem TNF-alfa. Os resultados mostraram uma taxa de resposta de 62%, incluindo dois pacientes com CR (10%), e uma sobrevida global mediana de 11 meses 20. Um estudo posterior informou sobre o resultado de 29 pacientes consecutivos tratados utilizando o melfalano sozinho. O resultado foi muito semelhante com uma resposta global de 62%, incluindo 10% de resposta completa e uma sobrevida média de 12 meses 21. Em um estudo realizado por Rizell et al., Foram incluídos 20 pacientes com melanoma uveal. Os pacientes foram divididos em três diferentes eras do tempo, e os resultados mostraram uma diminuição na mortalidade de 27% para 0%, devido a uma melhor seleção dos pacientes e desenvolvimento técnico 22. O conhecimento sobre IHP é baseada principalmente em séries menores retrospectiva única instituição, e os resultados publicados estão listadas na Tabela 1. Emresumo, a taxa de resposta global é 33-100%, incluindo uma taxa de resposta completa de 0-20%. A mortalidade pós-operatória é de 6% e a sobrevida média é de 12 meses. <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> Autor </td><td> n </td><td> Tipo </td><td> ORR </td><td> CR </td><td> A sobrevida média </td><td> Mortalidade </td></tr><tr><td> Alexander et al., 2000 </td><td> 22 </td><td> IHP </td><td> 62% </td><td> 10% </td><td> 11 meses </td><td> 5% </td></tr><tr><td> Alexander et al., 2003 </td><td> 29 </td><td> IHP </td><td> 62% </td><td> 10% </td><td> 12 meses </td><td> 0% </td></tr><tr><td> Noter et al., 2003 </td><td> 8 </td><td> IHP </td><td> 50% </td><td> 0% </td><td> 10 meses </td><td> 0% </td></tr><tr><td> Pingpank et al. 2005 </td><td> 10 </td><td> PHP </td><td> 50% </td><td> 20% </td><td> N / D </td><td> 0% </td></tr><tr><td> Rizell et al., 2008 </td><td> 27 </td><td> IHP </td><td> 70% </td><td> 7% </td><td> 13 meses </td><td> 22% </td></tr><tr><td> Verhoef et al., 2008 </td><td> 4 </td><td> IHHP </td><td> 100% </td><td> 0% </td><td> 9 meses </td><td> 0% </td></tr><tr><td> van Iersel et al., 2008 </td><td> 12 </td><td> IHP </td><td> 33% </td><td> 0% </td><td> 10 meses </td><td> 0% </td></tr><tr><td> van Etten et al., 2009 </td><td> 8 </td><td> IHHP </td><td> 37% </td><td> 0% </td><td> 11 meses </td><td> 0% </td></tr><tr><td> Média ponderada </td><td> 120 </td><td></td><td> 59% </td><td> 7% </td><td> 12 meses </td><td> 6% </td></tr><tr><td> Olofsson et al. </td><td> 34 </td><td> IHP </td><td> 68% </td><td> 12% </td><td> 24 meses60; </td><td> 0% </td></tr></tbody></table> Tabela 1:. Os resultados de perfusão hepática isolado publicações com os resultados clínicos notificados para os doentes com metástases hepáticas isoladas tratados com diferentes modalidades de perfusão hepática isolada. ORR = taxa de resposta global; CR = resposta completa; IHP = perfusão hepática isolada; IHHP = isolado perfusão hepática hipóxico; PHP = perfusão hepática percutânea; N / A = Não disponível. <img alt="Figura 1" src="/files/ftp_upload/52490/52490fig1.jpg" /> Figura 1:. Desenho esquemático do sistema de desvio veno-venosa e o sistema de perfusão A linha vermelha representa o cateter na artéria hepática e o azul representa o cateter na veia cava. Eles estão ligados a um sistema de perfusão que consiste de um oxigenador, uma bomba de cilindro e uma unidade de aquecimento. As linhas pretas representam a veno-venous sistema de derivação ligada a uma bomba de rolos.

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.

Isolado hepática Perfusão como um tratamento para o fígado Metástases de Uveal Melanoma

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

Nanyang Technological University

Research

JoVE Journal

Medicine

13.3K visualizações.  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.

Vídeo: 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.

Procedimentos cirúrgicos para um modelo de rato de Transplante de Fígado parcial ortotópico com reconstrução arterial hepática

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

Medicina

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.

Osteopático manipulativo tratamento como ferramenta adjuvante útil para 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 ...

Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts

The success of liver transplantation has resulted in a dramatic organ shortage. In most transplant regions 20-30% of patients on the waiting list for liver transplantation die without receiving an organ transplant or are delisted for disease progression. One strategy to increase the donor pool is the utilization of marginal grafts, such as fatty livers, grafts from older donors, or donation after cardiac death (DCD). The current preservation technique of cold static storage is only poorly tolerated by marginal livers resulting in significant organ damage. In addition, cold static organ storage does not allow graft assessment or repair prior to transplantation.
These shortcomings of cold static preservation have triggered an interest in warm perfused organ preservation to reduce cold ischemic injury, assess liver grafts during preservation, and explore the opportunity to repair marginal livers prior to transplantation. The optimal pressure and flow conditions, perfusion temperature, composition of the perfusion solution and the need for an oxygen carrier has been controversial in the past.
In spite of promising results in several animal studies, the complexity and the costs have prevented a broader clinical application so far. Recently, with enhanced technology and a better understanding of liver physiology during ex vivo perfusion the outcome of warm liver perfusion has improved and consistently good results can be achieved.
This paper will provide information about liver retrieval, storage techniques, and isolated liver perfusion in pigs. We will illustrate a) the requirements to ensure sufficient oxygen supply to the organ, b) technical considerations about the perfusion machine and the perfusion solution, and c) biochemical aspects of isolated organs.

Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts

Marginal grafts, such as fatty livers, grafts from older donors, or livers retrieved after cardiac death (DCD) tolerate conventional, cold static storage only poorly. We developed a novel model of subnormothermic ex vivo liver perfusion for preservation, assessment, and repair of marginal liver grafts prior to transplantation.

Técnica de Subnormothermic<em&gt; Ex Vivo</em&gt; Fígado de Perfusão para o armazenamento, Avaliação e Reparação de enxertos de fígado Marginal

The success of liver transplantation has resulted in a dramatic organ shortage. In most transplant regions 20-30% of patients on the waiting list for ...

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.

Um Modelo murino de metástases hepáticas pré-clínica

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.

Guiada por MRI dmPFC-EMTr como um tratamento para o Transtorno Depressivo Maior resistente ao tratamento

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.

Percutânea hepática Perfusão (PHP) com melfalano como um tratamento para Unresectable Metástases confinado ao fígado

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.

Geração de um humanizado rato Liver Usando células-tronco hepáticas humanas

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.

Método de entrega directa segmentos intra-hepática Usando um modelo de rato Liver Hilar Grampo

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.

Tratamento de metástases hepáticas, usando um método do Volume alvo interno para radioterapia estereotáxica corpo

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.

Um pequeno modelo Animal de perfusão de fígado normotérmica Ex Vivo

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