Name: application of hemostatic devices in laparoscopic hepatectomy
Uploaded: 2022-04-19T13:00:00
Description: Watch this Scientific Journal Video about Application of Hemostatic Devices in Laparoscopic Hepatectomy at JoVE.com

Este trabajo fue apoyado por subvenciones del Proyecto de Ciencia y Tecnología de la ciudad de Guangzhou (202102010090).

La operación es rutinaria y recibió la aprobación ética. Las aprobaciones son las siguientes: Aprobación para una revisión rápida por parte del Comité de Ética de Investigación Clínica y Aplicación del Segundo Hospital Afiliado de la Universidad Médica de Guangzhou: El proyecto de revisión de ética de investigación científica "Aplicación de dispositivos hemostáticos simples y fáciles en la hepatectomía laparoscópica" (número de aceptación: 2022-hg-ks-02) fue aprobado por el comité de ética de in...

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Y., Han, H. S., Yoon, Y. S., Shin, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Feasibility+of+laparoscopic+liver+resection+for+tumors+located+in+the+posterosuperior+segments+of+the+liver,+with+a+special+reference+to+overcoming+current+limitations+on+tumor+location.">Feasibility of laparoscopic liver resection for tumors located in the posterosuperior segments of the liver, with a special reference to overcoming current limitations on tumor location.</a> Surgery. 144 (1), 32-38 (2008).</li><li>Ome, Y., Honda, G., Doi, M., Muto, J., Seyama, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laparoscopic+anatomic+liver+resection+of+segment+8+using+intrahepatic+Glissonean+approach.">Laparoscopic anatomic liver resection of segment 8 using intrahepatic Glissonean approach.</a> Journal of the American College of Surgeons. 230 (3), 13-20 (2020).</li><li>Ryu, T., 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=Perioperative+and+oncological+outcomes+of+laparoscopic+anatomical+hepatectomy+for+hepatocellular+carcinoma+introduced+gradually+in+a+single+center.">Perioperative and oncological outcomes of laparoscopic anatomical hepatectomy for hepatocellular carcinoma introduced gradually in a single center.</a> Surgical Endoscopy. 32 (2), 790-798 (2018).</li><li>Makabe, K., 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=Efficacy+of+occlusion+of+hepatic+artery+and+risk+of+carbon+dioxide+gas+embolism+during+laparoscopic+hepatectomy+in+a+pig+model.">Efficacy of occlusion of hepatic artery and risk of carbon dioxide gas embolism during laparoscopic hepatectomy in a pig model.</a> Journal of Hepato-Biliary-Pancreatic Sciences. 21 (8), 592-598 (2014).</li><li>Miyagi, S., 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=Pure+laparoscopic+hepatectomy+combined+with+a+pure+laparoscopic+pringle+maneuver+in+patients+with+severe+cirrhosis.">Pure laparoscopic hepatectomy combined with a pure laparoscopic pringle maneuver in patients with severe cirrhosis.</a> Case Reports in Gastroenterology. 9 (1), 101-105 (2015).</li></ol>

La hepatectomía es uno de los métodos de tratamiento más importantes para los pacientes con cáncer primario de hígado y cáncer de hígado secundario. En 1991, Reich et al. aplicaron la laparoscopia para extirpar tumores benignos del hígado y completaron la primera hepatectomía laparoscópica del mundo4. Después de años de rápido desarrollo y promoción, la hepatectomía laparoscópica se ha convertido en uno de los métodos principales para tratar tumores malignos hepáticos y se ha lle...

El carcinoma hepatocelular es uno de los tumores malignos más comunes del sistema digestivo. Según los diferentes sitios primarios, se puede dividir en carcinoma hepatocelular primario y cáncer de hígado secundario. Las células pueden hacer metástasis desde tumores primarios desde órganos fuera del hígado hacia el hígado de varias maneras, lo que lleva a un carcinoma en el hígado. Se ha informado que más del 50% de las células metastásicas en el hígado provienen del cáncer colorrectal, mientras que otras son de tumores de mama, páncreas, pulmón y estómago, etc. 1. En los últimos años, muchos tratamientos para el cáncer de hígado secundario están disponibles, incluyendo quimioterapia sistemática, terapia intervencionista, terapia molecular dirigida, cirugía, etc.2. Sin embargo, la resección radical sigue siendo el tratamiento más efectivo porque puede eliminar completamente el cáncer3.
Con el rápido desarrollo de la tecnología laparoscópica, la hepatectomía anatómica laparoscópica es reconocida gradualmente por los cirujanos, pero aún no se realiza ampliamente, especialmente en las instituciones médicas primarias. Una de las razones es el requisito de dispositivos hemostáticos de alto grado. Estos son necesarios para reducir los riesgos de sangrado y fuga de bilis durante el proceso de operación. Aquí, presentamos un conjunto de equipos hemostáticos simples y fáciles, que incluyen un catéter de un solo lumen, bisturí armónico y electrocoagulación monopolo, para realizar hepatectomía laparoscópica. Para hacer esto, primero la porta hepatis se ocluye intermitentemente mediante el uso de un catéter de un solo lumen. El tejido del parénquima hepático se resecta mediante el uso del bisturí armónico. Las manchas sangrantes se coagulan mediante electrocoagulación monopolo punto a punto. Este equipo hemostático simple y fácil utiliza un catéter de un solo lumen para realizar la maniobra de pringle y utiliza la hemostasia del bisturí armónico y la electrocoagulación monopolo. El equipo se puede encontrar fácilmente en los hospitales, lo que proporciona una mayor facilidad para realizar laparoscopia o capacitación. Por lo tanto, estos dispositivos hemostáticos simples y fáciles son adecuados para realizar procedimientos en instituciones médicas primarias.
En este estudio, el paciente era un varón de 67 años diagnosticado con un adenocarcinoma moderadamente diferenciado del colon sigmoide con metástasis en el hígado. La resección radical del cáncer de colon sigmoide se realizó en enero de 2021. Los resultados patológicos fueron adenocarcinoma moderadamente diferenciado con el estadio TNM de pT4aN2aM1. La quimioterapia FOLFOX se administró cuatro veces después de la operación. Después de esto, la condición corporal del paciente se consideró adecuada para realizar una hepatectomía anatómica laparoscópica para eliminar completamente la lesión de las metástasis hepáticas. El grado de Función Hepática de Child-Pugh fue grado A. Para la prueba de función de reserva hepática, R15 en la prueba de aclaramiento de ICG fue del 1,6% (<10%). La TC mostró un tumor de 57 mm x 68 mm x 76 mm a través de la parte dorsal de S5 y la parte ventral de S6 del hígado; el modelo de reconstrucción tridimensional se muestra en la Figura 1.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>HARMONIC ACE Ultrasonic Surgical Devices</td>
			<td>Ethicon Endo-Surgery,LLC</td>
			<td>HAR36</td>
			<td></td>
		</tr>
		<tr>
			<td>Hem-o-lock</td>
			<td>Teleflex Medical</td>
			<td>544233</td>
			<td></td>
		</tr>
		<tr>
			<td>Monopole Electrocoagulation</td>
			<td>KANGJI MEDICAL</td>
			<td>/</td>
			<td></td>
		</tr>
		<tr>
			<td>single lumen ureter</td>
			<td>WELL LEAD MEDICAL CO.,LTD.</td>
			<td>12F</td>
			<td></td>
		</tr>
	</tbody>
</table>

application of hemostatic devices in laparoscopic hepatectomy

La hepatectomía laparoscópica se considera un método convencional para tratar enfermedades hepáticas benignas y malignas porque es un método mínimamente invasivo. A pesar de su aspecto no invasivo, el sangrado y la fuga de bilis se producen en la resección del tejido del parénquima hepático durante la operación o en el período posterior a la operación, lo que indica la necesidad de dispositivos hemostáticos de alto grado, como la aspiración quirúrgica ultrasónica, la electrocoagulación bipolar, etc. La falta de disponibilidad de estos dispositivos hemostáticos de alto grado impide que la hepatectomía laparoscópica se convierta en un procedimiento generalizado en las organizaciones médicas básicas. En vista de la situación mencionada anteriormente, se desarrolla un conjunto de dispositivos hemostáticos simples y fáciles en este protocolo, que incluye un bisturí armónico, electrocoagulación monopolo y un catéter de luz única, para realizar de manera innovadora la resección del tejido del parénquima hepático. En primer lugar, la porta hepatis o pedículo hepático se ocluye intermitentemente mediante un catéter de un solo lumen, seguido de pinzamiento durante 15 min y liberación durante 5 min. Posteriormente, utilizando el bisturí armónico, se realiza el pinzamiento y el aplastamiento del hígado para cortar el tejido del parénquima hepático y revelar las arterias intrahepáticas, las venas y los conductos biliares. Por último, las manchas sangrantes se coagulan mediante electrocoagulación monopolar en cada punto. Las estructuras de la tubería intrahepática son visibles mediante el uso de estos métodos, que podrían detener el sangrado fácilmente, reducir la tasa de incidencia de fugas de bilis y mejorar la seguridad y la viabilidad de la hepatectomía laparoscópica. Por lo tanto, los dispositivos hemostáticos simples y fáciles que se muestran aquí son adecuados para realizar procedimientos en instituciones médicas primarias.

La operación se completó en 2,5 h y el volumen de sangrado intraoperatorio fue de 100 ml sin la transfusión de sangre. No hubo complicaciones a corto plazo, y el paciente fue dado de alta del hospital el día 8 despuésde la operación. El nivel de antígeno carcinoembrionario (CEA) después de la operación disminuyó a 110,64 μg/L desde el nivel previo a la operación de 1058,69 μg/L (Figura 12). Dos meses después de la operación, el paciente regresó al hospital para con...

Watch this Scientific Journal Video about Application of Hemostatic Devices in Laparoscopic Hepatectomy at JoVE.com

Application of Hemostatic Devices in Laparoscopic Hepatectomy

Los dispositivos hemostáticos de alto grado son esenciales para la hepatectomía laparoscópica. Sin embargo, estos dispositivos no están generalizados en las organizaciones médicas básicas. Por lo tanto, en este artículo se muestra un conjunto de dispositivos hemostáticos simples y fáciles, que pueden hacer que la hepatectomía laparoscópica sea más fácil de realizar.

Aplicación de dispositivos hemostáticos en la hepatectomía laparoscópica

Laparoscopic hepatectomy is considered a conventional method for treating benign and malignant liver diseases because it is a minimally invasive method. ...

La principal ventaja de esta técnica es que el dispositivo hemostático es simple y fácil de obtener y se puede llevar a cabo en hospitales básicos. Este conjunto de equipos hemostáticos se puede aplicar aún más a la hepatectomía laparoscópica y otros sistemas. Es muy recomendable tener una cierta base de cirugía laparoscópica, especialmente el uso experto de un bisturí armónico para aplicar este conjunto de dispositivos hemostáticos en la hepatectomía laparoscópica.Comience aplicando punción directa para establecer neumoperitoneo en laparoscopia. Coloque un trócar de 10 milímetros en cada orificio de observación en el área subumbilical, la línea clavicular media derecha debajo del margen costal y la línea media ventral. Luego coloque un trocar de cinco milímetros en la línea auxiliar anterior derecha y la línea media ventral.Ensamble los dispositivos hemostáticos a partir del bisturí armónico, la electrocoagulación monopolo y el catéter de un solo lumen para ser utilizados de manera innovadora en la resección del tejido del parénquima hepático. Para realizar una maniobra de Pringle, ocluya la primera porta hepatis de forma intermitente mediante el uso de un catéter de un solo lumen. Sujete el catéter de lúmenes con un clip hemostático durante 15 minutos seguido de soltarlo durante cinco minutos usando el bisturí armónico para cortar el clip y sacar el clip para restaurar el suministro de sangre a la primera porta hepatis.Separe los pedículos hepáticos que irrigan el tumor. Resecarlos y dividirlos uno por uno con un bisturí armónico. Observe la línea de isquemia en la superficie del hígado, que se hace visible después de la resección de los pedículos hepáticos.Usa el gancho para marcarlo. Reseque el tejido del parénquima hepático con el bisturí armónico mientras sujeta y aplasta el hígado gradualmente. Observe la arteria hepática interna, la vena y el conducto biliar.Reseque y divida estas estructuras de tuberías. Una vez que aparezca el sangrado, coagule las manchas de sangrado en la superficie de disección hepática inmediatamente utilizando la electrocoagulación monopolo punto a punto. Use el pedículo hepático posterior derecho como señal para la resección del tejido del parénquima intrahepático.Reserve el pedículo hepático posterior principal y diseccione la rama de los pedículos que irrigan el tumor. Para completar la operación, lave la superficie del hígado para que uno pueda ver si todavía hay manchas de sangrado. Detenga el sangrado en la superficie de disección hepática y extraiga la muestra tumoral de la cavidad abdominal.La operación se completó en 2,5 horas. El volumen de sangrado intraoperatorio fue de 100 mililitros sin la transfusión de sangre y no se observaron complicaciones a corto plazo. El nivel de antígeno carcinoembrionario después de la operación disminuyó a 110.64 microgramos por litro desde el nivel previo a la operación de 1058.69 microgramos por litro.El tratamiento de quimioterapia se reanudó dos meses después de la operación, de acuerdo con los resultados de la patología tumoral. El examen de TC postoperatorio se comparó con el TC preoperatorio y no se observaron signos de rebrote tumoral. El paso más importante en el proceso quirúrgico es el uso del bisturí armónico.Se requiere una buena cantidad de habilidad para evitar daños a estructuras vitales.

application-of-hemostatic-devices-in-laparoscopic-hepatectomy

Research

JoVE Journal

Cancer Research

Evaporation-reducing Culture Condition Increases the Reproducibility of Multicellular Spheroid Formation in Microtiter Plates

Tumor models that closely imitate in vivo conditions are becoming increasingly popular in drug discovery and development for the screening of potential anti-cancer drugs. Multicellular tumor spheroids (MCTSes) effectively mimic the physiological conditions of solid tumors, making them excellent in vitro models for lead optimization and target validation. Out of the various techniques available for MCTS culture, the liquid-overlay method on agarose is one of the most inexpensive methods for MCTS generation. However, the reliable transfer of MCTS cultures using liquid-overlay for high-throughput screening may be compromised by a number of limitations, including the coating of microtiter plates (MPs) with agarose and the irreproducibility of uniform MCTS formation across wells. MPs are significantly prone to edge effects that result from excessive evaporation of medium from the exterior of the plate, preventing the use of the entire plate for drug tests. This manuscript provides detailed technical improvements to the liquid-overlay technique to increase the scalability and reproducibility of uniform MCTS formation. Additionally, details on a simple, semi-automatic, and universally applicable software tool for the evaluation of MCTS features after drug treatment is presented.

The uneven loss of medium from microtiter plates affects the reproducibility of uniform multicellular tumor spheroid formation. Improving culture conditions to reduce significant medium loss will improve the reproducibility of spheroid formation and the results of spheroid-based assays using the liquid-overlay technique.

La evaporación de reducción de Cultura condición aumenta la reproducibilidad del esferoide multicelular Formación en placas de microtitulación

Tumor models that closely imitate in vivo conditions are becoming increasingly popular in drug discovery and development for the screening of potential ...

Investigación

Investigación sobre el cáncer

Application of Laser Micro-irradiation for Examination of Single and Double Strand Break Repair in Mammalian Cells

Highly coordinated DNA repair pathways exist to detect, excise and replace damaged DNA bases, and coordinate repair of DNA strand breaks. While molecular biology techniques have clarified structure, enzymatic functions, and kinetics of repair proteins, there is still a need to understand how repair is coordinated within the nucleus. Laser micro-irradiation offers a powerful tool for inducing DNA damage and monitoring the recruitment of repair proteins. Induction of DNA damage by laser micro-irradiation can occur with a range of wavelengths, and users can reliably induce single strand breaks, base lesions and double strand breaks with a range of doses. Here, laser micro-irradiation is used to examine repair of single and double strand breaks induced by two common confocal laser wavelengths, 355 nm and 405 nm. Further, proper characterization of the applied laser dose for inducing specific damage mixtures is described, so users can reproducibly perform laser micro-irradiation data acquisition and analysis.

Confocal fluorescence microscopy and laser micro-irradiation offer tools for inducing DNA damage and monitoring the response of DNA repair proteins in selected sub-nuclear areas. This technique has significantly advanced our knowledge of damage detection, signaling, and recruitment. This manuscript demonstrates these technologies to examine single and double strand break repair.

Aplicación de Micro-la irradiación del Laser para la examinación de Single y doble filamento romper reparación en células de mamíferos

Highly coordinated DNA repair pathways exist to detect, excise and replace damaged DNA bases, and coordinate repair of DNA strand breaks. While molecular ...

Laparoscopic Pancreatoduodenectomy With Modified Blumgart Pancreaticojejunostomy

Minimally invasive pancreatic resections are technically demanding but rapidly increasing in popularity. In contrast to laparoscopic distal pancreatectomy, laparoscopic pancreatoduodenectomy (LPD) has not yet obtained wide acceptance, probably due to technical challenges, especially regarding the pancreatic anastomosis.
The study describes and demonstrates all steps of LPD, including the modified Blumgart pancreaticojejunostomy. Indications for LPD are all pancreatic and peri-ampullary tumors without vascular involvement. Relative contra-indications are body mass index &#62;35 kg/m2, chronic pancreatitis, mid-cholangiocarcinomas and large duodenal cancers.
The patient is in French position, 6 trocars are placed, and dissection is performed using an (articulating) sealing device. A modified Blumgart end-to-side pancreaticojejunostomy is performed with 4 large needles (3/0) barbed trans-pancreatic sutures and 4 to 6 duct-to-mucosa sutures using 5/0 absorbable multifilament combined with a 12 cm, 6 or 8 Fr internal stent using 3D laparoscopy. Two surgical drains are placed alongside the pancreaticojejunostomy.
The described technique for LPD including a modified Blumgart pancreatico-jejunostomy is well standardized, and its merits are currently studied in the randomized controlled multicenter trial. This complex operation should be performed at high-volume centers where surgeons have extensive experience in both open pancreatic surgery and advanced laparoscopic gastro-intestinal surgery.

Laparoscopic pancreatoduodenctomy (LPD) may offer advantages over open pancreatoduodenectomy, including early postoperative mobilization, less delayed gastric emptying and a shorter hospital stay. However, LPD is technically challenging and not well-standardized, especially regarding the pancreatic anastomosis. We describe a standardized technique for the pancreatic anastomosis during LPD: modified Blumgart pancreaticojejunostomy.

Duodenopancreatectomía laparoscópica con Blumgart Pancreaticojejunostomy modificado

Minimally invasive pancreatic resections are technically demanding but rapidly increasing in popularity. In contrast to laparoscopic distal ...

The Application of 1% Methylene Blue Dye As a Single Technique in Breast Cancer Sentinel Node Biopsy

In this study, we injected 1% methylene blue dye (MBD) into the subareolar or peritumoral space of the breast. In the case of breast conserving surgery (BCS), a separate incision in the lower axilla hairline was made to find the sentinel nodes (SNs). In mastectomy, the SNs were identified through the same mastectomy incision. The SNs were described as blue nodes or nodes with lymphatic blue channels. An anatomical landmark in the axilla was used to facilitate SNs identification. The SNs metastases were evaluated by intraoperative frozen section analysis and histopathology examination as it is a gold standard. Here, we described the MBD as the lone technique in breast cancer sentinel node biopsy (SNB) which could be useful when radioisotope tracer or patent or isosulfan blue dye (PBD) cannot be provided.

In Indonesia, sentinel node biopsy (SNB) is not routinely performed for breast cancer surgery because of the limitation to provide radioisotope tracer and isosulfan or patent blue dye (PBD). To overcome this obstacle, we applied 1% methylene blue dye (MBD) as a single agent to map the sentinel nodes (SNs).

La aplicación del 1% de tinte azul de metileno como una sola técnica en la biopsia de ganglio centinela de cáncer de mama

In this study, we injected 1% methylene blue dye (MBD) into the subareolar or peritumoral space of the breast. In the case of breast conserving surgery ...

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

Glioblastoma is the most common and lethal form of brain cancer, with a median survival of 15 months after diagnosis and a 5 year survival rate of only 5% with current standard of care. Tumors often recur within 9 months following initial surgery, radiation and chemotherapy, at which point treatment options become limited. This highlights the pressing need for the development of better therapeutics to prolong survival and increase the quality of life for these patients.
Tumor Treating Fields (TTFields) therapy was developed to take advantage of the effect of low frequency alternating electrical fields on cells for cancer therapy. TTFields have been demonstrated to disrupt cells during mitosis and slow tumor growth. There is also growing evidence that they act through stimulating immune responses within exposed tumors. The advantages of TTFields therapy include its noninvasive approach and increased quality of life compared to other treatment modalities such as cytotoxic chemotherapies. The Food and Drug Administration approved TTFields therapy for the treatment of recurrent glioblastoma in 2011 and for newly diagnosed glioblastoma in 2015. We report on the effects of TTFields during mitosis, the results of electric fields modeling, and proper transducer array placement. Our protocol outlines the clinical application of TTFields on a patient post-surgery, using the second-generation device.

Glioblastoma is the most common and aggressive primary brain malignancy in adults, with most tumors recurring after initial treatment. Tumor Treating Fields (TTFields) therapy is the newest treatment modality for glioblastoma. Here, we describe the proper application of TTFields-transducer arrays on patients and discuss theory and aspects of treatment.

La aplicación clínica de Tumor tratamiento de terapia de campos en Glioblastoma

Glioblastoma is the most common and lethal form of brain cancer, with a median survival of 15 months after diagnosis and a 5 year survival rate of only 5% ...

In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells

Tumorigenesis is a multi-step process in which cells acquire capabilities&#160;that allow their growth, survival, and dissemination under hostile conditions. Different tests seek to identify and quantify these hallmarks of cancerous cells; however, they often focus on a single aspect of cellular transformation and, in fact, multiple tests are required for their proper characterization. The purpose of this work is to provide researchers with a set of tools to assess cellular transformation in vitro from a broad perspective, thereby making it possible to draw sound conclusions.
A sustained proliferative signaling activation is the major feature of tumoral tissues and can be easily monitored under in vitro conditions by calculating the number of population doublings achieved over time. Besides, the growth of cells in 3D cultures allows their interaction with surrounding cells, resembling what occurs in vivo. This enables the evaluation of cellular aggregation and, together with immunofluorescent labeling of distinctive cellular markers, to obtain information on another relevant feature of tumoral transformation: the loss of proper organization. Another remarkable characteristic of transformed cells is their capacity to grow without attachment to other cells and to the extracellular matrix, which can be evaluated with the anchorage assay.
Detailed experimental procedures to evaluate cell growth rate, to perform immunofluorescent labeling of cell lineage markers in 3D cultures, and to test anchorage-independent cell growth in soft agar are provided. These methodologies are optimized for Breast Primary Epithelial Cells (BPEC) due to its relevance in breast cancer; however, procedures can be applied to other cell types after some adjustments.

This protocol provides experimental in vitro tools to evaluate the transformation of human mammary cells. Detailed steps to follow-up cell proliferation rate, anchorage-independent growth capacity, and distribution of cell lineages in 3D cultures with basement membrane matrix are described.

Evaluación In Vitro de la Transformación Oncogénica en Células Epiteliales Mamarias Humanas

Tumorigenesis is a multi-step process in which cells acquire capabilities&#160;that allow their growth, survival, and dissemination under hostile ...

Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions

Pediatric high-grade gliomas (pHGG) represent childhood and adolescent brain cancers that carry a rapid dismal prognosis. Since there is a need to overcome the resistance to current treatments and find a new way of cure, modeling the disease as close as possible in an in vitro setting to test new drugs and therapeutic procedures is highly demanding. Studying their fundamental pathobiological processes, including glutamatergic neuron hyperexcitability, will be a real advance in understanding interactions between the environmental brain and pHGG cells. Therefore, to recreate neurons/pHGG cell interactions, this work shows the development of a functional in vitro model co-culturing human-induced Pluripotent Stem (hiPS)-derived cortical glutamatergic neurons pHGG cells into compartmentalized microfluidic devices and a process to record their electrophysiological modifications. The first step was to differentiate and characterize human glutamatergic neurons. Secondly, the cells were cultured in microfluidic devices with pHGG derived cell lines. Brain microenvironment and neuronal activity were then included in this model to analyze the electrical impact of pHGG cells on these micro-environmental neurons. Electrophysiological recordings are coupled using multielectrode arrays (MEA) to these microfluidic devices to mimic physiological conditions and to record the electrical activity of the entire neural network. A significant increase in neuron excitability was underlined in the presence of tumor cells.

Recent works uncover the neuronal impact on high-grade pediatric glioma (pHGG) cells and their reciprocal interactions. The present work shows the development of an in vitro model co-culturing pHGG cells and glutamatergic neurons and recorded their electrophysiological interactions to mimic those interactivities.

Cocultivo de neuronas glutamatérgicas y células pediátricas de glioma de alto grado en dispositivos microfluídicos para evaluar las interacciones eléctricas

Pediatric high-grade gliomas (pHGG) represent childhood and adolescent brain cancers that carry a rapid dismal prognosis. Since there is a need to ...

Flexible Organic Electronic Devices for Pulsed Electric Field Therapy of Glioblastoma

Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed electric fields (PEFs) are promising for the improvement of treatment efficiency. However, they rely on rigid electrodes that cause acute and chronic damage, especially in soft tissues such as the brain. In this work, flexible electronics were used to deliver PEFs to tumors and the biological response was evaluated with fluorescent microscopy. Interdigitated gold electrodes on a thin, transparent parylene-C substrate were coated with the conducting polymer PEDOT:PSS, resulting in a conformable and biocompatible device. The effects of PEFs on tumors and their microenvironment were examined using various biological models. First, monolayers of glioblastoma cells were cultured on top of the electrodes to investigate phenomena in vitro. As an intermediate step, an in ovo model was developed where engineered tumor spheroids were grafted in the embryonic membrane of a quail. Due to the absence of an immune system, this led to highly vascularized tumors. At this early stage of development, embryos have no immune system, and tumors are not recognized as foreign bodies. Thus, they can develop fast while developing their own vessels from the existing embryo vascular system, which represents a valuable 3D cancer model. Finally, flexible electrode delivery of PEFs was evaluated in a complete organism with a functional immune system, using a syngenic, orthograft (intracranial) mouse model. Tumor spheroids were grafted into the brain of transgenic multi-fluorescent mice prior to the implantation of flexible organic electrode devices. A sealed cranial window enabled multiphoton imaging of the tumor and its microenvironment during treatment with PEFs over a period of several weeks.

This work describes the development of flexible interdigitated electrodes for implementation in 3D brain tumor models, namely, in vitro culture, in ovo model, and in vivo murine model. The proposed method can be used to evaluate the effects of pulsed electric fields on tumors at different levels of complexity.

Dispositivos electrónicos orgánicos flexibles para la terapia de campo eléctrico pulsado del glioblastoma

Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed ...

Generation and Culturing of High-Grade Serous Ovarian Cancer Patient-Derived Organoids

Organoids are 3D dynamic tumor models that can be grown successfully from patient-derived ovarian tumor tissue, ascites, or pleural fluid and aid in the discovery of novel therapeutics and predictive biomarkers for ovarian cancer. These models recapitulate clonal heterogeneity, the tumor microenvironment, and cell-cell and cell-matrix interactions. Additionally, they have been shown to match the primary tumor morphologically, cytologically, immunohistochemically, and genetically. Thus, organoids facilitate research on tumor cells and the tumor microenvironment and are superior to cell lines. The present protocol describes distinct methods to generate patient-derived ovarian cancer organoids from patient tumors, ascites, and pleural fluid samples with a higher than 97% success rate. The patient samples are separated into cellular suspensions by both mechanical and enzymatic digestion. The cells are then plated utilizing a basement membrane extract (BME) and are supported with optimized growth media containing supplements specific to the culturing of high-grade serous ovarian cancer (HGSOC). After forming initial organoids, the PDOs can sustain long-term culture, including passaging for expansion for subsequent experiments.

Patient-derived organoids (PDO) are a three-dimensional (3D) culture that can mimic the tumor environment in vitro. In high-grade serous ovarian cancer, PDOs represent a model to study novel biomarkers and therapeutics.

Generación y cultivo de organoides derivados de pacientes con cáncer de ovario seroso de alto grado

Organoids are 3D dynamic tumor models that can be grown successfully from patient-derived ovarian tumor tissue, ascites, or pleural fluid and aid in the ...

Application of the En Bloc Concept Combined with Anatomic Resection in Laparoscopic Hepatectomy

Laparoscopic hepatectomy has been reported in many studies, and it is the mainstream method of liver resection. In some particular cases, such as when there are tumors adjacent to the cystic bed, surgeons cannot palpate the surgical margins through the laparoscopic approach, which leads to uncertainty about R0 resection. Conventionally, the gallbladder is resected first, and the hepatic lobes or segments are resected second. However, tumor tissues can be disseminated in the above cases. To address this issue, based on the recognition of the porta hepatis and intrahepatic anatomy, we propose a unique approach to hepatectomy combined with gallbladder resection by en bloc anatomic resection in situ. Firstly, after dissecting the cystic duct, without cutting the gallbladder primarily, the porta hepatis is pre-occluded by the single lumen ureter; secondly, the left hepatic pedicle is made free by the gap of the Laennec membrane and Hilar plate; thirdly, the assistant is asked to drag the fundus of the gallbladder, and the liver parenchyma tissue is resected using a harmonic scalpel along the ischemia line on the liver surface and intraoperative ultrasound. The whole middle hepatic vein (MHV) and its tributaries appear completely; lastly, the left hepatic vein (LHV) is disconnected, and the specimen is taken out from the abdominal cavity. The tumor, gallbladder, and other surrounding tissues are resected en bloc, which meets the tumor-free criterion, and a wide incisal margin and R0 resection are achieved. Therefore, the laparoscopic hepatectomy with the combination of the en bloc concept and anatomic resection is a safe, effective, and radical method with low postoperative recurrence and metastasis.

Numerous studies have demonstrated the advantages of anatomic resection. Nonetheless, whether anatomic resection can increase R0 resection rates remains controversial. Consequently, the present study describes an innovative procedure involving the en bloc concept combined with anatomic resection in laparoscopic hepatectomy, which can reduce postoperative recurrence and metastasis.

Aplicación del concepto En Bloc combinado con resección anatómica en hepatectomía laparoscópica

Laparoscopic hepatectomy has been reported in many studies, and it is the mainstream method of liver resection. In some particular cases, such as when ...