Orthotopic Liver Transplantation in Rats

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat ...

manufacturing-devices-instruments-for-easier-rat-liver

Manufacturing Devices and Instruments for Easier Rat Liver Transplantation

Orthotopic rat liver transplantation is a popular model, which has been shown in a recent JoVE paper with the use of the "quick-linker" device. This ...

reduced-complications-after-arterial-reconnection-rat-model

Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation ...

University of Geneva Hospitals

University of Pavia 

University Health Network

The clinical success of liver transplantation is founded upon years of experimental research. Since Kamada and colleagues developed the "two-cuff" technique, the rat has become the best model for extensive investigations. Although the Kamada technique is technically complex and not easy to master, it is still the mainstay of orthotopic liver transplantation in rodents. We have developed a modified three-cuff version of this technique that facilitates anastomosis and markedly reduces warm ischemia time.

A novel technique for rat liver transplantation using Quick Linker system: a preliminary result.

Le succ&egrave;s clinique de transplantation h&eacute;patique repose sur des ann&eacute;es de recherches exp&eacute;rimentales. Depuis Kamada et coll&egrave;gues a d&eacute;velopp&eacute; la technique de &quot;deux-brassard&quot;, le rat est devenu le meilleur mod&egrave;le pour une enqu&ecirc;te approfondie. Bien que la technique de Kamada est techniquement complexe et pas facile &agrave; ma&icirc;tre, c&#39;est toujours la clef de vo&ucirc;te de la transplantation h&eacute;patique orthotopique chez les rongeurs. Nous avons d&eacute;velopp&eacute; une version modifi&eacute;e de la trois-brassard de cette technique qui facilite l&#39;anastomose et r&eacute;duit sensiblement les temps d&#39;isch&eacute;mie chaude.

Une nouvelle technique pour la transplantation de foie de rat en utilisant le syst&egrave;me d&#39;&eacute;diteur de liens rapides : un r&eacute;sultat pr&eacute;liminaire.

Il successo clinico di trapianto di fegato &egrave; fondato su anni di ricerca sperimentale. Poich&eacute; Kamada e colleghi ha sviluppato la tecnica &quot;due-bracciale&quot;, il ratto &egrave; diventato il miglior modello per approfondite indagini. Sebbene la tecnica Kamada &egrave; tecnicamente complessa e non facile da maestro, &egrave; ancora il pilastro del trapianto ortotopico di fegato nei roditori. Abbiamo sviluppato una versione modificata del tre-bracciale di questa tecnica che facilita l&#39;anastomosi e notevolmente riduce il tempo di ischemia calda.

Una romanzo tecnica per il trapianto di fegato di ratto con sistema Quick Linker: un risultato preliminare.

Donor-specific allogeneic loading can prolong the survival of solid organ transplants by inducing a state known as acceptance. Several populations of cells are known to be involved in this process, but their exact roles have yet to be defined. The aim of this study was to assess the effects of portal-vein transfusion of donor-specific splenocytes (DST) after short-term cyclosporine A (CyA) therapy in pigs subjected to renal transplantation.

Short-term cyclosporine therapy and cotransplantation of donor splenocytes: effects on graft rejection and survival rates in pigs subjected to renal transplantation.

Propres donneurs allog&eacute;nique chargement peut prolonger la survie des transplantations d&#39;organes solides en induisant un &eacute;tat connu comme acceptation. Plusieurs populations de cellules sont connues pour &ecirc;tre impliqu&eacute;es dans ce processus, mais leurs r&ocirc;les exacts restent &agrave; d&eacute;finir. Le but de cette &eacute;tude &eacute;tait d&#39;&eacute;valuer les effets de la veine transfusion de spl&eacute;nocytes donneur sp&eacute;cifiques (DST) apr&egrave;s la ciclosporine &agrave; court terme une th&eacute;rapie (ACY) chez les porcs soumise &agrave; la transplantation r&eacute;nale.

Th&eacute;rapie &agrave; court terme de cyclosporine et cotransplantation des spl&eacute;nocytes de donateurs : effets sur les taux de rejet et de la survie de greffe chez les porcs soumis &agrave; la transplantation r&eacute;nale.

Specifiche del donatore allogenico caricamento pu&ograve; prolungare la sopravvivenza dei trapianti di organi solidi da indurre uno stato noto come accettazione. Diverse popolazioni di cellule sono noti per essere coinvolti in questo processo, ma i loro ruoli esatti devono ancora essere definito. Lo scopo di questo studio era di valutare gli effetti di trasfusione vena del donatore-specifica splenocytes (DST) dopo a breve termine ciclosporina (CyA) terapia nei suini sottoposti a trapianto renale.

Terapia a breve termine di ciclosporina e cotransplantation del donatore splenocytes: gli effetti sui tassi di rifiuto e la sopravvivenza dell&#39;innesto nei suini sottoposti a trapianto renale.

The aim of the present study was to assess the efficiency of cell-based immune assays in the detection of alloreactivity after islet transplantation and to correlate these results with clinical outcome. Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients (n = 14), donors, or third party. The immune reactivity was assessed by the release of IFN-Î³ (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine quantification (Bioplex). Islet function correlated with the number of IFN-Î³-secreting cells following incubation with donor cells (p = 0.007, r = -0.50), but not with third party cells (p = 0.61). Similarly, a high number of donor-specific proliferating cells was associated with a low islet function (p = 0.006, r = -0.51). Proliferating cells were mainly CD3(+)CD4(+) lymphocytes and CD3(-)CD56(+) natural killer cells (with low levels of CD3(+)CD8(+) lymphocytes). Patients with low islet function had increased levels of CD4(+)Ki67(+)cells (p â‰¤ 0.0001), while no difference was observed in CD8(+)Ki67(+) and CD56(+)Ki67(+) cells. IFN-Î³, IL-5, and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFN-Î³-ELISpot, proliferation, and cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 Â± 0.088, 0.85 Â± 0.084, and 0.88 Â± 0.074, respectively). Cellular immune reactivity against donor cells correlates with posttransplant islet function. The tested assays have the potential to be of substantial help in the management of islet graft recipients and deserve prospective validation.

Posttransplant cellular immune reactivity against donor antigen correlates with clinical islet transplantation outcome: towards a better posttransplant monitoring.

Le but de cette &eacute;tude &eacute;tait d&#39;&eacute;valuer l&#39;efficacit&eacute; des analyses cellulaires immunitaires dans la d&eacute;tection des alloreactivity apr&egrave;s la transplantation d&#39;&icirc;lots et de corr&eacute;ler ces r&eacute;sultats avec des r&eacute;sultats cliniques. Lymphocytaire mixte cultures ont &eacute;t&eacute; r&eacute;alis&eacute;es avec des cellules mononucl&eacute;aires de sang p&eacute;riph&eacute;rique des b&eacute;n&eacute;ficiaires (n = 14), donateurs, ou tierce partie. La r&eacute;activit&eacute; immunitaire a &eacute;t&eacute; &eacute;valu&eacute;e par la lib&eacute;ration d&#39;IFN-&gamma; (ELISpot), la prolif&eacute;ration des cellules (analyse de FACS pour Ki67) et quantification de cytokine (Bioplex). Fonction de l&#39;&icirc;lot en corr&eacute;lation avec le nombre de cellules s&eacute;cr&eacute;trices d&#39;IFN-&gamma; apr&egrave;s incubation avec les cellules du donneur (p = 0, 007, r = -0.50), mais pas avec des cellules de tierce partie (p = 0,61). De m&ecirc;me, un nombre &eacute;lev&eacute; de cellules en prolif&eacute;ration donneur sp&eacute;cifique a &eacute;t&eacute; associ&eacute; &agrave; une fonction d&#39;&icirc;lot faible (p = 0,006, r = -0,51). Les cellules en prolif&eacute;ration ont &eacute;t&eacute; principalement lymphocytes CD3(+)CD4(+) et CD3(-)CD56(+) des cellules tueuses naturelles (ayant un faible niveau de lymphocytes CD3(+)CD8(+)). Patients dont la fonction faible &icirc;lot avaient augment&eacute; le taux de CD4 (+) Ki67 (+) des cellules (p &le; 0,0001), alors qu&#39;aucune diff&eacute;rence a &eacute;t&eacute; observ&eacute;e dans les cellules CD8(+)Ki67(+) et CD56(+)Ki67(+). IFN-&gamma;, IL-niveaux 5 et IL-17 ont augment&eacute; chez les patients dont la fonction &icirc;lot faible, mais IL-10 niveaux avaient tendance &agrave; &ecirc;tre plus faibles. IFN-&gamma;-ELISpot, prolif&eacute;ration et cytokines &eacute;taient de m&ecirc;me pr&eacute;cis pour pr&eacute;dire les r&eacute;sultats cliniques (AUC = 0,77 &plusmn; 0,088, 0,85 &plusmn; 0,084 et &plusmn; 0,88 0,074, respectivement). Cellulaire r&eacute;activit&eacute; immunitaire contre les cellules du donneur est corr&eacute;l&eacute;e avec la fonction &icirc;lot posttransplantation. Les dosages test&eacute;s ont le potentiel pour &ecirc;tre d&#39;une aide substantielle dans la gestion des destinataires de greffe &icirc;lot et m&eacute;ritent la validation prospective.

Posttransplantation r&eacute;activit&eacute; immunitaire cellulaire contre l&#39;antig&egrave;ne du donneur est corr&eacute;l&eacute;e avec le r&eacute;sultat de transplantation clinique &icirc;lot : vers une meilleure surveillance posttransplantation.

Lo scopo del presente studio era di valutare l&#39;efficienza dell&#39;analisi immune cell-based nella rilevazione di alloreactivity dopo trapianto isolotto e correlare questi risultati con esito clinico. Colture miste linfocitarie sono state eseguite con cellule mononucleate di sangue periferico da destinatari (n = 14), donatori, o terze parti. La reattivit&agrave; immunitaria &egrave; stata valutata dal rilascio di IFN-&gamma; (ELISpot), la proliferazione cellulare (analisi FACS per Ki67) e quantificazione delle citochine (Bioplex). Funzione isolotto correlato con il numero di cellule che secernono IFN-&gamma; dopo incubazione con cellule del donatore (p = 0.007, r = -0,50), ma non con le cellule di terze parti (p = 0,61). Allo stesso modo, un elevato numero di cellule proliferanti specifiche del donatore &egrave; stato associato con una funzione di basso isolotto (p = 0.006, r = 060x). Le cellule in proliferazione sono stati principalmente linfociti CD3(+)CD4(+) e CD3(-)CD56(+) le cellule natural killer (con bassi livelli di linfociti CD3(+)CD8(+)). Pazienti con funzione di basso isolotto avevano aumentato i livelli di CD4 (+) Ki67 (+) cellule (p &le; 0,0001), mentre nessuna differenza &egrave; stata osservata nelle cellule CD8(+)Ki67(+) e CD56(+)Ki67(+). IFN-&gamma;, IL-5 e IL-17 livelli sono stati aumentati nei pazienti con funzione di basso isolotto, ma livelli di IL-10 tendevano ad essere pi&ugrave; basso. IFN-&gamma;-ELISpot, proliferazione e citochine erano similmente accurata nel predire l&#39;esito clinico (AUC = 0.77 &plusmn; 0.088, 0.85 &plusmn; 0.084 e 0.88 &plusmn; 0.074, rispettivamente). Cellulare reattivit&agrave; immunitaria contro le cellule del donatore correla con funzione isolotto infettivo. I dosaggi testati hanno il potenziale per essere di notevole aiuto nella gestione dei destinatari dell&#39;innesto isolotto e meritano convalida futuro.

Infettivo reattivit&agrave; immunitaria cellulare contro l&#39;antigene donatore correla con esito trapianto clinico isolotto: verso un migliore monitoraggio infettivo.

INTRODUCTION: Post-operative pancreatic fistula (POPF) is a common complication after partial pancreatic resection, and is associated with increased rates of sepsis, mortality and costs. The role of fibrin sealants in decreasing the risk of POPF remains debatable. The aim of this study was to evaluate the literature regarding the effectiveness of fibrin sealants in pancreatic surgery. METHODS: A comprehensive database search was conducted. Only randomized controlled trials comparing fibrin sealants with standard care were included. A meta-analysis regarding POPF, intra-abdominal collections, post-operative haemorrhage, pancreatitis and wound infections was performed according to the recommendations of the Cochrane collaboration. RESULTS: Seven studies were included, accounting for 897 patients. Compared with controls, patients receiving fibrin sealants had a pooled odds ratio (OR) of developing a POPF of 0.83 [95% confidence interval (CI): 0.6-1.14], P = 0.245. There was a trend towards a reduction in post-operative haemorrhage (OR = 0.43 (95%CI: 0.18-1.0), P = 0.05) and intra-abdominal collections (OR = 0.52 (95%CI: 0.25-1.06), P = 0.073) in those patients receiving fibrin sealants. No difference was observed in terms of mortality, wound infections, re-interventions or hospital stay. CONCLUSION: On the basis of these results, fibrin sealants cannot be recommended for routine clinical use in the setting of pancreatic resection.

Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection.

INTRODUCTION : Fistule pancr&eacute;atique post-op&eacute;ratoire (POPF) est une complication fr&eacute;quente apr&egrave;s r&eacute;section pancr&eacute;atique partielle et est associ&eacute;e &agrave; une augmentation des taux de septic&eacute;mie, de mortalit&eacute; et de co&ucirc;ts. Le r&ocirc;le des mastics de fibrine en diminuant le risque de POPF reste discutable. Le but de cette &eacute;tude &eacute;tait d&#39;&eacute;valuer la litt&eacute;rature au sujet de l&#39;efficacit&eacute; des mastics de fibrine dans la chirurgie du pancr&eacute;as. M&eacute;thodes : Une recherche de base de donn&eacute;es compl&egrave;te a &eacute;t&eacute; r&eacute;alis&eacute;e. Seulement des essais comparatifs randomis&eacute;s comparant les scellants de fibrine aux soins ont &eacute;t&eacute; inclus. Une m&eacute;ta-analyse concernant les collections intra-abdominale, h&eacute;morragie postop&eacute;ratoire, POPF, infections pancr&eacute;atite et la plaie a &eacute;t&eacute; r&eacute;alis&eacute;e conform&eacute;ment aux recommandations de la Cochrane collaboration. R&Eacute;SULTATS : Sept &eacute;tudes ont &eacute;t&eacute; incluses, soit 897 patients. Par rapport aux t&eacute;moins, les patients recevant des mastics de fibrine avaient un mise en commun d&#39;odds ratio (OR) de mettre au point un POPF de 0,83 [intervalle de confiance 95 % (IC): 0,6-1, 14], P = 0,245. Il y avait une tendance vers une r&eacute;duction dans l&#39;h&eacute;morragie post-op&eacute;ratoire (ou = 0,43 ([IC95:: 0,18-1.0), P = 0,05) et collections intra-abdominale (ou = 0,52 (IC95:: 0,25-1,06), P = 0,073) chez les patients recevant des mastics de fibrine. Aucune diff&eacute;rence n&#39;a &eacute;t&eacute; observ&eacute;e en termes de mortalit&eacute;, les infections de plaie, de r&eacute;-interventions ou d&#39;h&ocirc;pital rester. CONCLUSION : Sur la base de ces r&eacute;sultats, scellants de fibrine ne peut pas &ecirc;tre recommand&eacute;es pour utilisation clinique en routine dans le cadre de la r&eacute;section du pancr&eacute;as.

Revue syst&eacute;matique et m&eacute;ta-analyse des mastics de fibrine pour les patients subissant une r&eacute;section du pancr&eacute;as.

Introduzione: Fistola pancreatica post-operatoria (POPF) &egrave; una complicanza comune dopo parziale resezione del pancreas ed &egrave; associato con tassi di incremento della sepsi, mortalit&agrave; e costi. Il ruolo dei sigillanti di fibrina nel diminuire il rischio di POPF rimane discutibile. Lo scopo di questo studio era di valutare la letteratura riguardanti l&#39;efficacia dei sigillanti di fibrina nella chirurgia del pancreas. Metodi: &Egrave; stata condotta una ricerca nel database globale. Solo controllati randomizzati confrontando sigillanti di fibrina con cure standard sono stati inclusi. Una meta-analisi per quanto riguarda POPF, raccolte intra-addominale, emorragia post-operatoria, infezioni pancreatite e ferita &egrave; stata eseguita secondo le raccomandazioni della Cochrane collaboration. RISULTATI: Sette studi sono stati inclusi, contabilit&agrave; per 897 pazienti. Rispetto ai controlli, i pazienti che ricevono sigillanti fibrina avevano un pool odds ratio (OR) di sviluppare una POPF di 0,83 [95% intervallo di confidenza (CI): 0,6-1.14], P = 0.245. C&#39;era una tendenza verso una riduzione nell&#39;emorragia post-operatoria (o = 0.43 (IC 95%: 0,18-1.0), P = 0,05) e raccolte intra-addominale (o = 0.52 (95% CI: 0.25-1,06), P = 0.073) in quei pazienti che ricevono sigillanti di fibrina. &Egrave; stata osservata alcuna differenza in termini di mortalit&agrave;, infezioni della ferita, re-interventi o ospedale soggiorno. CONCLUSIONE: Sulla base di questi risultati, sigillanti di fibrina non possono essere raccomandati per uso clinico di routine nell&#39;impostazione di resezione pancreatica.

Revisione sistematica e meta-analisi di sigillanti di fibrina per pazienti sottoposti a resezione pancreatica.

Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of .

ArticleTotal : 3	Year
Publication title Cited by 31	2012
Publication title Cited by 1	2013
Publication title Cited by 4	2020

Article	Year
A novel technique for rat liver transplantation using Quick Linker system: a preliminary result. The Journal of surgical research\| PubMed ID: 18468634	2008
Short-term cyclosporine therapy and cotransplantation of donor splenocytes: effects on graft rejection and survival rates in pigs subjected to renal transplantation. The Journal of surgical research\| PubMed ID: 18561953	2008
Posttransplant cellular immune reactivity against donor antigen correlates with clinical islet transplantation outcome: towards a better posttransplant monitoring. Cell transplantation\| PubMed ID: 22963841	2012
Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection. HPB : the official journal of the International Hepato Pancreato Biliary Association\| PubMed ID: 23461684	2013
Recent advances in liver transplantation for cancer: The future of transplant oncology. JHEP reports : innovation in hepatology\| PubMed ID: 32039389	2019

Graziano Oldani

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