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

Los pacientes por escrito el consentimiento informado y el estudio fue aprobado por el Consejo Regional de Revisión Ética de la Universidad de Gotemburgo. 1. Anestesia <ol><li> Configure todo el seguimiento (ECG, manguito de presión arterial) 17. </li><li> Inserte un catéter epidural en la parte baja a mediados nivel torácico 17. </li><li> Inducir la anestesia con propofol 2 mg / kg, 150 g de fentanilo y rocuronio 0,6 mg / kg a través de un catéter venoso periférico insertado previamente. </li><li> Preoxigenar y intubar al paciente. Mantener la anestesia con sevoflurano, oxígeno y aire 17. </li><li> Inserte un catéter venoso central de doble luz y un catéter arterial. Monitorear CVP y arterial presión 17. </li></ol> 2. Aislamiento del Hígado y la canulación de los buques <ol><li> Administrar 100 IE / kg de heparina y dar profilaxis antibiótica (por ejemplo, 160 mg de trimetoprima y 800 mg de sulfametoxazol). </li><li> Utilizando la técnica de Seldinger percutánea, coloque un catéter 17 Fr en la vena femoral y un catéter 15 Fr en la vena yugular externa 18. Verifique la posición de los catéteres por fluoroscopia. </li><li> Realice una laparotomía por una incisión en forma de L de la apófisis xifoides hasta la línea media y luego se extendió a una incisión subcostal derecha 19. </li><li> Verifique que no existan metástasis extrahepáticas en el abdomen por una inspección completa y la palpación. <ol><li> Si se encuentra alguna lesión sospechosa, verificar malignidad en la sección congelada. </li><li> Terminar el procedimiento si hay evidencia de manifestación extrahepática (adenopatía periaortal, metástasis abdominales). Adenopatías en la porta del hígado no se considera una contraindicación. </li></ol></li><li> Movilizar el hígado dividiendo el ligamento falciforme, el ligamento triangular izquierdo y derecho y el ligamento coronario 19. </li><li> Diseccionar la vena cavavenosa a partir de las venas renales hasta el diafragma con la ligadura de venas tributarias retroperitoneales. </li><li> Identificar la vena suprarrenal derecha y colocar un asa vascular alrededor. </li><li> Identificar la vena gonadal derecha. Diseccionarlo para 5-10 cm. Coloque una sutura en bolsa de tabaco alrededor de la entrada de la vena cava. <ol><li> Coloque una ligadura distal de la vena gonadal. Con la tijera, abrir la vena gonadal 3-5 cm de la vena cava. </li><li> Inserte un 18 P. catéter reforzado con alambre a través de la vena gonadal derecha y coloque la punta retrohepatically encima de las venas renales. </li><li> Colocar una ligadura alrededor de la vena gonadal para asegurar la posición del catéter. </li><li> Verificar el retorno de la sangre a través del catéter. Heparinizar el catéter 18. </li></ol></li><li> Diseccionar el ligamento hepatoduodenal y visualizar la arteria hepática común, la arteria gastroduodenal y la arteria hepática propia. <ol><li> Lugar buque bucles alrededor del arte hepático comúnRY y la arteria gastrodoudenal. </li><li> Diseccionar la vena porta y colocar un asa vascular alrededor. </li><li> Aislar el resto del ligamento que contiene el conducto biliar común y incluir todo esto en un bucle buque. </li></ol></li><li> Levante la arteria gastroduodenal con el bucle buque. Después de interrumpir el flujo arterial, hacer una incisión con tijeras. <ol><li> Inserte un 8-12 Fr catéter con la punta dentro de la arteria hepática propia. Fije la posición con una ligadura alrededor de la arteria gastroduodenal. </li><li> Verificar retorno de la sangre en el catéter y luego se heparinizar 18. </li></ol></li><li> Primer sistema de perfusión con una unidad de hematíes, 100 ml de albúmina (50 g / L), 100 ml de Tribonat (bicarbonato de sodio), 2500 unidades de heparina (5000 IE / ml) y 250 ml de cristaloides. </li><li> Conectar el arterial y los catéteres de vena cava en el sistema de perfusión que consisten de una máquina corazón-pulmón equipado con una bomba de rodillos y un calentador tunto con venosas sistemas de depósito, oxigenadores y tubos de tipo desechable. </li><li> Conectar los catéteres yugulares femorales y externos a la bomba de derivación venovenosa que consta de una bomba centrífuga, junto con una unidad de calefacción y empezar bypass. </li><li> Completar el aislamiento del hígado apretando un torniquete de Rumel alrededor de la vena cava infrahepatically encima de las venas renales y la sujeción de la vena cava suprahepatically mediante una abrazadera vascular Klintmalm. <ol><li> Apriete un torniquete de Rumel alrededor del conducto biliar común, la vena porta y la vena suprarrenal derecha y finalmente fijar la arteria hepática usando una pinza vascular. </li></ol></li></ol> 3. La perfusión <ol><li> Iniciar la perfusión y controlar manualmente el nivel de sangre en el depósito venoso. Ajustar la velocidad de flujo hasta que se alcanza un nivel de estado estacionario, por lo general una velocidad de flujo entre 500-1,200 ml / min. </li><li> Coloque las sondas de termistor en los lóbulos derecho e izquierdo del hígado y uno directamente enel catéter arterial. </li><li> Calentar el líquido de perfusión destinado a una temperatura de hígado objetivo de 40 o C. Mantener esta temperatura durante toda la perfusión. </li><li> Colocar una sonda de centelleo sobre la cabeza de la bomba de bypass veno-venosa. </li><li> Calibrar el sistema de monitoreo de fugas, mediante la inyección de una pequeña dosis de 10 MBq 99m Tc-albúmina (1 ml) a la circulación sistémica y registrar la actividad de línea de base. <ol><li> Inyectar una dosis diez veces superior, 100 MBq 99m Tc-albúmina (1 ml), en la unidad de perfusión hepática. </li><li> Registrar cualquier fuga del sistema de perfusión a la circulación sistémica como un aumento en la actividad medida por la sonda de centelleo. </li><li> Registre cualquier fuga de la circulación sistémica al sistema de perfusión como un aumento en el volumen en el depósito venoso. </li></ol></li><li> Cuando se establece en estado estacionario de la velocidad de flujo, no hay fugas está presente y la temperatura de hígado ha alcanzado 40 ° C, se inyectan melfalán en una dosis de1 mg / kg de peso corporal en el sistema de perfusión dividido en dos dosis administradas 30 min aparte. </li></ol> 4. Poner fin a la perfusión y quitar catéteres <ol><li> Después de 60 minutos de perfusión, vaciar el líquido de perfusión del sistema y regar el hígado con 1000 ml de cristaloides. </li><li> Añadir una unidad de hematíes a la unidad de la perfusión, infundir en el hígado y luego detener la perfusión. </li><li> Suelte la abrazadera Klintmalm y el torniquete de Rumel de la vena cava. </li><li> Suelte el torniquete de Rumel del ligamento hepatoduodenal. </li><li> Retire la ligadura de la arteria gastroduodenal. Retire el catéter y ligar el vaso. </li><li> Soltar la abrazadera de la arteria hepática. </li><li> Retirar el catéter de la vena gonadal y ligar el vaso. </li><li> Parar la bomba de bypass veno-venoso y desconectar los tubos. </li><li> Cierre el abdomen con una sutura fascial ininterrumpida y luego una sutura intradérmica piel. </li><li> Quite la catheters en las venas femoral y yugular externas y aplican presión local durante 5 min. </li></ol> 5. Cuidado posoperatorio <ol><li> Retirar la intubación del paciente y transferir a la unidad de cuidados postoperatorios durante 24 horas. Mantener el seguimiento de la presión venosa central y la presión sanguínea arterial. </li><li> Traslado al paciente a un departamento de cirugía para un típico de 3-7 días de cuidados postoperatorios. </li><li> Continuar con heparina de bajo peso molecular (HBPM) a una dosis de 5000 IE / día para un total de 4 semanas. </li></ol>

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The authors have nothing to disclose.

Los pacientes con melanoma uveal metastásico tienen pocas opciones terapéuticas. Quimioterapia 6, inmunoterapia 23 y terapia dirigida 24 no han sido capaces de demostrar una mejoría de SG. Para los pacientes con pocas metástasis hepáticas, la resección hepática es una opción 12. Otros tratamientos incluyen quimioterapia hepática intraarterial (EIS) 9, la quimioembolización transarterial (TACE) 25 y la terapia selectiva interna radiación (SIRT) 26. PHI es una intervención quirúrgica importante y complejo, y desde el primer informe por Ausman ha habido muchos avances en la técnica quirúrgica. En 2004, van Etten y sus colegas informaron los primeros resultados clínicos utilizando la técnica de perfusión aislada hepática hipóxica (IHHP) 27. A principios de 1990, tres grupos independientes desarrollaron un novedoso sistema de perfusión hepática percutánea (PHP) utilizando quimiofiltración extracorpórea 28-30. Ningún estudiola comparación de estas técnicas a PHI se han realizado. Los informes hasta ahora no parecen estar a favor de cualquier técnica específica. Selección de los pacientes es de gran importancia para este tratamiento. Dado que es un tratamiento local, no debe haber ninguna evidencia de enfermedad extrahepática. Debido al riesgo de desarrollar insuficiencia hepática, no más de 50% del volumen del hígado debe ser sustituido por tumor 22. Los pacientes deben tener un buen estado funcional (ECOG 0-1) y no de corazón, pulmonar, del de riñón o enfermedad del hígado que podría aumentar el riesgo de morbilidad severa después de la cirugía. En un reciente estudio de fase II de nuestro grupo, se demostró una supervivencia media de 26 meses, lo que implica un potencial beneficio en la supervivencia de 14 meses, en comparación con un grupo control de 16. Para verificar este hallazgo, un ensayo de fase III aleatorizado multicéntrico entre el PHI y Mejor Cuidado Alternativo (BAC) ha comenzado recientemente en Escandinavia (el juicio ESCANDIO, número ClinicalTrials: NCT01.785.316). El tratamiento BAC puede incluir todas las otras opciones de tratamiento, ya sea existentes o experimentales, con la idea de que cruce no está permitido por la tasa de alcoholemia al grupo PHI. Los criterios de inclusión incluyen biopsia verificado metástasis hepáticas y sin evidencia de manifestaciones tumorales extrahepáticas por PET-CT. El objetivo primario es la supervivencia global a los 24 meses con los objetivos secundarios, incluyendo la tasa de respuesta, la supervivencia libre de progresión y la calidad de vida. La inclusión prevista es de 78 pacientes durante 5 años. En resumen, todavía existe ningún tratamiento que en los ensayos de fase III ha mostrado ningún supervivencia global prolongada para los pacientes con melanoma uveal metástasis hepáticas. PHI es una terapia regional interesante y prometedor donde los beneficios potenciales de la supervivencia en la actualidad están siendo investigados en un ensayo aleatorio (el juicio ESCANDIO).

El melanoma uveal es el tumor maligno intraocular primario más común en adultos, con una incidencia más alta de ser en poblaciones caucásicas 1. El tratamiento local consiste en la enucleación o placa local de radioterapia 2,3. Independientemente de tratamiento local, la enfermedad metastásica, en última instancia desarrollar en aproximadamente 35-50% de los pacientes 4,5. El hígado es el sitio más común de metástasis y aproximadamente el 50% de los pacientes presentan metástasis hepáticas aisladas. La mediana de supervivencia global (SG) para los pacientes con metástasis hepáticas es de 6-12 meses 4. Varios diferentes estrategias sistémicas y regionales de tratamiento se han explorado, pero las tasas de supervivencia no han mejorado 2. El tratamiento con quimioterapia sistémica, tanto sola sustancia (dacarbazina o temozolomida 6) o la combinación de tratamientos (régimen BOLD 7, gemcitabina con treosulfano 8), muestra tasas de respuesta de menos de10%. Quimioterapia intraarterial hepática (EIS) ha mostrado una tasa ligeramente superior de respuesta global en comparación con la quimioterapia sistémica, pero no un incremento en la supervivencia general 9. La quimioembolización transarterial (TACE) con cisplatino y carboplatino mostraron una respuesta parcial en el 57% de los pacientes con una supervivencia media de 9 meses 10. Radioterapia interna selectiva (SIRT) ha mostrado una respuesta parcial en el 62% de los pacientes con una supervivencia media de 7 meses 11. En un estudio sobre la resección hepática, incluyendo 255 pacientes, se informó de una supervivencia global de 14 meses; en 76 de los pacientes en los que era posible una resección microscópicamente completa, la supervivencia fue de 27 meses 12. Perfusión hepática aislada (PHI) es una opción de tratamiento regional, originalmente desarrollado por Ryan y Ausman. El fundamento de la técnica consiste en aislar quirúrgicamente y perfundir el hígado con una alta dosis de un agente quimioterapéutico, evitando sistémica axicidad 13. Además, la hipertermia concurrente media un aumento de la captación del agente quimioterapéutico por los cambios en el flujo sanguíneo del tumor y la permeabilidad de la membrana celular 14. Aislamiento vascular completa se confirma con una técnica trazador radioactivo utilizando Tc-99 etiquetados albúmina sérica humana 15. Una retrospectiva estudio de fase II ha demostrado un potencial beneficio de supervivencia de 14 meses (26 frente a 12 meses) para los pacientes que se sometieron a PHI en comparación con las más longevas con metástasis hepáticas melanoma uveal en Suecia 16. Aquí presentamos la técnica del PHI con una breve revisión de los resultados actuales y 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

La perfusión hepática aislada (PHI) es un procedimiento donde el hígado es aislado y perfundido con una alta concentración de la melfalán agente quimioterapéutico quirúrgicamente. Brevemente, el procedimiento se inicia con la configuración de una veno-venosa de bypass percutáneo de la vena femoral hasta la vena yugular externa. A través de una laparotomía, se insertan catéteres en la arteria hepática adecuada y la vena cava. La vena porta y la vena cava, tanto supra y infrahepatically, se fijan entonces. El catéteres arteriales y venosos están conectados a una máquina de corazón-pulmón y el hígado se perfunde con melfalán (1 mg / kg de peso corporal) durante 60 min. De esta manera es posible localmente perfundir el hígado con una alta dosis de un agente quimioterapéutico, sin fugas a la circulación sistémica. En estudios anteriores, que incluyeron pacientes con metástasis hepáticas aisladas de melanoma uveal, una tasa de respuesta global del 33-100% y una mediana de supervivencia entre 9 y 13 meses,han sido reportados. El objetivo de este protocolo es para dar una descripción clara de cómo llevar a cabo el procedimiento y debatir PHI como una opción de tratamiento para las metástasis hepáticas de melanoma uveal.

Un informe inicial incluyó 22 pacientes tratados con melfalán con o sin TNF-alfa. Los resultados mostraron una tasa de respuesta global del 62%, incluyendo dos pacientes con CR (10%), y una mediana de supervivencia global de 11 meses 20. Un estudio posterior informó sobre los resultados de 29 pacientes consecutivos tratados usando melfalán solo. El resultado fue muy similar con una respuesta global 62% incluyendo 10% de respuesta completa y una supervivencia media de 12 meses 21. En un estudio realizado por Rizell et al., Se incluyeron 20 pacientes con melanoma uveal. Los pacientes fueron divididos en tres eras de tiempo diferente, y los resultados mostraron una disminución de la mortalidad del 27% al 0% debido a una mejor selección de los pacientes y el desarrollo técnico 22. El conocimiento sobre el PHI se basa principalmente en pequeña retrospectiva serie de una sola institución, y los resultados publicados se enumeran en la Tabla 1. Enresumen, la tasa de respuesta general es de 33-100%, incluyendo una tasa de respuesta completa 0-20%. La mortalidad postoperatoria es del 6% y la mediana de supervivencia es de 12 meses. <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> Autor </td><td> n </td><td> Tipo </td><td> TRG </td><td> CR </td><td> La mediana de supervivencia </td><td> Mortalidad </td></tr><tr><td> Alexander et al. 2000 </td><td> 22 </td><td> PHI </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> PHI </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> PHI </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 / A </td><td> 0% </td></tr><tr><td> Rizell et al. 2008 </td><td> 27 </td><td> PHI </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> PHI </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> Media 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> PHI </td><td> 68% </td><td> 12% </td><td> 24 meses60; </td><td> 0% </td></tr></tbody></table> Tabla 1:. Los resultados de la perfusión hepática aislada Publicaciones con resultados clínicos reportados en pacientes con metástasis hepáticas aisladas tratados con diferentes modalidades de perfusión hepática aislada. TRG = tasa de respuesta global; CR = respuesta completa; PHI = perfusión hepática aislada; IHHP = aislado perfusión hepática hipóxico; PHP = perfusión hepática percutánea; N / A = No disponible. <img alt="Figura 1" src="/files/ftp_upload/52490/52490fig1.jpg" /> Figura 1:. Imagen esquemática del sistema de derivación veno-venosa y el sistema de perfusión La línea roja representa el catéter en la arteria hepática y el azul representa el catéter en la vena cava. Están conectados a un sistema de perfusión que consiste en un oxigenador, una bomba de rodillos y una unidad de calefacción. Las líneas negras representan la venosistema de derivación -venous conectado a una bomba de rodillos.

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.

Aislado hepática de perfusión como un tratamiento para las metástasis hepáticas de melanoma uveal

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 vistas.  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.

Procedimientos Quirúrgicos para un modelo de rata de trasplante hepático ortotópico parcial con reconstrucción arterial hepática

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

Investigación

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.

Manipulación Osteopática como herramienta complementaria útil para la Neumonía

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; Perfusión hepática para el Almacenamiento, Evaluación y Reparación de marginales injertos hepáticos

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.

A preclínicos modelo murino de metástasis hepática

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.

RM guiada dmPFC-rTMS como tratamiento para el trastorno depresivo mayor resistente al tratamiento

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.

Percutánea hepática perfusión (PHP) con melfalán como un tratamiento para la metástasis no resecables limitado al hígado

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.

Generación de un ratón humanizado hígado uso de células madre 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 la entrega directa segmentaria intra-hepática utilizando un modelo de hígado de rata hiliar abrazadera

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.

Tratamiento de las metástasis hepáticas mediante un método de volumen objetivo interno para radioterapia estereotáctica del cuerpo

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.

Un pequeño modelo de la perfusión hepática 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, ...