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

Dette arbeidet ble støttet av tilskudd fra Science and Technology Project of Guangzhou City (202102010090).

Operasjonen er rutinemessig og fikk etikkgodkjenning. Godkjenningene er som følger: Godkjenning for rask gjennomgang av klinisk forskning og applikasjonsetikkkomiteen til det andre tilknyttede sykehuset ved Guangzhou Medical University: Det vitenskapelige forskningsetiske gjennomgangsprosjektet "Anvendelse av enkle og enkle hemostatiske enheter i Laparoskopisk hepatektomi" (akseptnrr.: 2022-hg-ks-02) ble godkjent av den kliniske forsknings- og søknadsetikkkomiteen til Det andre tilknyttede sykehuset i Guangzhou Medical...

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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>

Hepatektomi er en av de viktigste behandlingsmetodene for pasienter med primær leverkreft og sekundær leverkreft. I 1991 påførte Reich et al. laparoskopi for å fjerne godartede svulster i leveren og fullførte verdens første laparoskopiske hepatektomi4. Etter år med rask utvikling og markedsføring har laparoskopisk hepatektomi blitt en av de vanlige metodene for å behandle lever ondartede svulster og har blitt mye utført de siste årene. Med fordelene med mindre intraoperativ blødning, ...

Hepatocellulært karsinom er en av de vanligste ondartede svulstene i fordøyelsessystemet. Ifølge de forskjellige primære stedene kan det deles inn i primær hepatocellulært karsinom og sekundær leverkreft. Celler kan metastasere fra primære svulster fra organer utenfor leveren til leveren på ulike måter, noe som fører til karsinom i leveren. Det har blitt rapportert at mer enn 50% av metastatiske celler i leveren kommer fra kolorektal kreft, mens andre er fra bryst-, bukspyttkjertel-, lunge- og magesvulster, etc1. I de senere år er mange behandlinger for sekundær leverkreft tilgjengelig, inkludert systematisk kjemoterapi, intervensjonsterapi, molekylær målrettet terapi, kirurgi, etc2. Imidlertid er radikal reseksjon fortsatt den mest effektive behandlingen fordi den helt kan fjerne kreften3.
Med den raske utviklingen av laparoskopisk teknologi blir laparoskopisk anatomisk hepatektomi gradvis anerkjent av kirurger, men er fortsatt ikke mye utført, spesielt i primære medisinske institusjoner. En av grunnene er kravet til høyverdige hemostatiske enheter. Disse er nødvendige for å redusere risikoen for blødning og gallelekkasje under driftsprosessen. Her presenterer vi et sett med enkelt og enkelt hemostatisk utstyr, inkludert et enkelt lumenkateter, harmonisk skalpell og monopole elektrokoagulasjon, for å utføre laparoskopisk hepatektomi. For å gjøre dette, først er porta hepatis okkludert periodisk ved hjelp av et enkelt lumenkateter. Lever parenchyma vev blir deretter resected ved hjelp av harmonisk skalpell. Blødningsflekker koagulert av monopol elektrokoagulasjon punkt-til-punkt. Dette enkle og enkle hemostatiske utstyret bruker et enkelt lumenkateter for å utføre pringlemanøveren og utnytter hemostase av den harmoniske skalpellen og monopole elektrokoagulasjonen. Utstyret finnes enkelt på sykehus, og gir dermed ekstra letthet for å utføre laparoskopi eller trening. Dermed er disse enkle og enkle hemostatiske enhetene egnet for å utføre prosedyrer i primære medisinske institusjoner.
I denne studien var pasienten en 67 år gammel mann diagnostisert med et moderat differensiert adenokarsinom av sigmoid kolon metastasert i leveren. Radikal reseksjon av sigmoid tykktarmskreft ble utført i januar 2021. De patologiske resultatene ble moderat differensiert adenokarsinom med TNM-fasen av pT4aN2aM1. FOLFOX kjemoterapi ble gitt fire ganger etter operasjonen. Etter dette ble pasientens kroppstilstand ansett som egnet til å utføre laparoskopisk anatomisk hepatektomi for å fjerne lesjonen av levermetastaser helt. Child-Pugh graden av leverfunksjon var grad A. For leverreservefunksjonstesten var R15 i ICG-clearance-testen 1,6% (<10%). CT viste en 57 mm x 68 mm x 76 mm svulst over dorsaldelen av S5 og ventral del av S6 i leveren; den tredimensjonale rekonstruksjonsmodellen er vist i figur 1.

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	<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

Laparoskopisk hepatektomi regnes som en konvensjonell metode for behandling av godartede og ondartede leversykdommer fordi det er en minimal invasiv metode. Til tross for det ikke-invasive aspektet, forekommer blødning og gallelekkasje i leverparenchyma vev reseksjon under operasjonen eller i etteroperasjonsperioden, noe som indikerer kravet til høyverdige hemostatiske enheter, for eksempel ultralyd kirurgisk aspirasjon, bipolar elektrokoagulasjon, etc. Mangelen på tilgjengelighet av disse høyverdige hemostatiske enhetene forhindrer at laparoskopisk hepatektomi blir en generalisert prosedyre i grunnleggende medisinske organisasjoner. I lys av situasjonen nevnt ovenfor, er en pakke med enkle og enkle hemostatiske enheter utviklet i denne protokollen, som inkluderer en harmonisk skalpell, monopole elektrokoagulasjon og et enkelt lumenkateter, for innovativt å utføre leverparenchyma vev reseksjon. Først av alt er porta hepatis eller lever pedicle okkludert periodisk av et enkelt lumenkateter, etterfulgt av klemming i 15 minutter og frigjøring i 5 minutter. Deretter gjøres det å bruke den harmoniske skalpellen, klemming og knusing av leveren for å kutte av leverparenchymavevet og for å avsløre intrahepatiske arterier, årer og gallekanaler. Til slutt koagulerte blødningsflekkene ved hjelp av monopolelektrokoagulasjon på hvert sted. Intrahepatiske rørledningsstrukturer er da synlige ved hjelp av disse metodene, noe som kan stoppe blødning lett, redusere forekomsten av gallelekkasje og forbedre sikkerheten og gjennomførbarheten av laparoskopisk hepatektomi. Derfor er de enkle og enkle hemostatiske enhetene som vises her, egnet for å utføre prosedyrer i primære medisinske institusjoner.

Operasjonen ble fullført innen 2,5 timer og det intraoperative blødningsvolumet var 100 ml uten blodoverføring. Det var ingen kortsiktige komplikasjoner, og pasienten ble utskrevet fra sykehusetden 8. Karcinoembryonic antigen (CEA) nivå etter operasjonen redusert til 110,64 μg/L fra føroperasjonsnivået på 1058,69 μg/L (figur 12). To måneder etter operasjonen returnerte pasienten til sykehuset for å fortsette kjemoterapibehandlingen (kjemoterapiregimet var mFOLFOX6). Kje...

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

Application of Hemostatic Devices in Laparoscopic Hepatectomy

Høyverdige hemostatiske enheter er avgjørende for laparoskopisk hepatektomi. Disse enhetene er imidlertid ikke generalisert i grunnleggende medisinske organisasjoner. Derfor vises en pakke med enkle og enkle hemostatiske enheter i denne artikkelen, noe som kan gjøre laparoskopisk hepatektomi lettere å utføre.

Påføring av hemostatiske enheter i Laparoskopisk hepatektomi

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

Den største fordelen med denne teknikken er at hemostatisk enhet er enkel og enkel å skaffe og kan utføres på grunnleggende sykehus. Dette settet med hemostatisk utstyr kan brukes videre på laparoskopisk hepatektomi og andre systemer. Det anbefales på det sterkeste å ha et visst grunnlag for laparoskopisk kirurgi, spesielt dyktig bruk av en harmonisk skalpell for å bruke dette settet med hemostatiske enheter i laparoskopisk hepatektomi.Begynn med å bruke direkte punktering for å etablere pneumoperitoneum i laparoskopi. Plasser en 10 millimeter trokar i hvert observasjonshull i det subumbiliske området, høyre midtklavicular linje under kostnadsmarginen og ventral midtlinje. Plasser deretter en fem millimeter trokar i høyre fremre hjelpelinje og den ventrale midtlinjen.Monter de hemostatiske enhetene fra den harmoniske skalpellen, monopole elektrokoagulasjonen og enkelt lumenkateter som skal brukes innovativt i leverparenchyma vev reseksjon. For å utføre en Pringle manøver, okkludere den første porta hepatis periodisk ved hjelp av en enkelt lumen kateter. Klem lumenkateteret med et hemostatisk klips i 15 minutter etterfulgt av å slippe det i fem minutter ved hjelp av den harmoniske skalpellen for å kutte av klipsen og ta klipsen ut for å gjenopprette blodtilførselen til de første porta-hepatiene.Skill lever pedicles som forsyner svulsten. Resect og dele dem en etter en med en harmonisk skalpell. Vær oppmerksom på iskemilinjen på leveroverflaten, som blir synlig etter reseksjon av leverpediplene.Bruk kroken til å merke den. Resect leveren parenchyma vev ved hjelp av harmonisk skalpell mens klemme og knuse leveren gradvis. Vær oppmerksom på den indre leverarterien, venen og gallekanalen.Resect og del disse rørledningsstrukturene. Når blødning vises, koaguler blødningsflekkene på lever disseksjonsoverflaten umiddelbart ved hjelp av punkt-til-punkt monopol elektrokoagulasjon. Bruk riktig bakre lever pedicle som et skilt for intrahepatisk parenchyma vev reseksjon.Reserver de viktigste bakre leverprippene og disseker grenen av pedikler som forsyner svulsten. For å fullføre operasjonen, vask leveroverflaten slik at man kan se om det fortsatt er blødningsflekker. Stopp blødningen på lever disseksjonsoverflaten og fjern tumorprøven fra bukhulen.Operasjonen ble fullført innen 2,5 timer. Det intraoperative blødningsvolumet var 100 milliliter uten blodoverføring og ingen kortsiktige komplikasjoner ble observert. Karcinoembryonic antigen nivå etter operasjonen redusert til 110,64 mikrogram per liter fra pre-drift nivå av 1058.69 mikrogram per liter.Kjemoterapibehandlingen ble gjenopptatt to måneder etter operasjonen, ifølge tumorpatologiresultatene. Den postoperative CT-undersøkelsen ble sammenlignet med preoperativ CT og ingen tegn på tumor gjenvekst ble observert. Det viktigste trinnet i den kirurgiske prosessen er bruken av den harmoniske skalpellen.En god del dyktighet er nødvendig for å unngå skade på vitale strukturer.

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.

Fordampning reduserende Kultur Forhold Øker reproduserbarhet av Flercellede spheroid Dannelse i mikrotiterplater

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

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.

Bruk av Laser mikro-bestråling for undersøkelse av enkelt og dobbelt Strand pause reparasjon i pattedyrceller

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.

Laparoskopisk Pancreatoduodenectomy med endrede Blumgart Pancreaticojejunostomy

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).

Anvendelsen av 1% metylen blå fargestoff som en enkelt teknikk i brystkreft Sentinel node biopsi

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.

Klinisk anvendelse av svulst behandling av feltene terapi i glioblastom

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.

In Vitro evaluering av onkogen transformasjon i humane pattedyr epitelceller

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.

Samkultur av glutamatergeiske nevroner og pediatriske gliomaceller av høy kvalitet til mikrofluidiske enheter for å vurdere elektriske interaksjoner

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.

Fleksible organiske elektroniske enheter for pulserende elektrisk feltterapi av glioblastom

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.

Generering og dyrking av høygradig serøs eggstokkreft Pasientavledede organoider

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.

Anvendelse av En Bloc-konseptet kombinert med anatomisk reseksjon ved laparoskopisk hepatektomi

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