Détection Moléculaire Des Bêta-cellules De Circulation Après La Transplantation D'îlots

Diabetes. Mar, 2002  |  Pubmed ID: 11872650

La transplantation d'îlots est un traitement prometteur pour le diabète de type 1. Toutefois, les greffes d'îlots sont soumis à de multiples blessures, y compris la toxicité des médicaments immunosuppresseurs, l'hyperglycémie, l'hypoxie, des réactions inflammatoires non spécifiques, ainsi que l'allo-et la destruction auto-immune. Les approches thérapeutiques à ces mécanismes d'endommagement nécessitent une détection précoce des lésions îlot, qui n'est actuellement pas possible en raison de l'absence de marqueurs efficaces. Basé sur l'hypothèse de l'îlot de dissociation et la libération de cellules des îlots pancréatiques dans la circulation pendant des blessures îlot, nous avons conçu un test très sensible et spécifique moléculaire, capable de détecter deux bêta-cellules par millilitre de sang veineux par RT-PCR de l'ARNm de l'insuline. Nous signalons que circulent des cellules bêta peut être démontrée jusqu'à 10 semaines après la transplantation d'îlots intraportale, évaluée au bout de six greffes d'îlots sur quatre diabétiques de type 1. En outre, nos résultats suggèrent que la période pendant laquelle circulent les cellules des îlots peuvent être détectés peut dépendre de l'environnement du greffon et du traitement immunosuppresseur. Ce test peut permettre une meilleure estimation de la perte de cellules d'îlots et l'identification des facteurs impliqués dans la greffe d'îlots blessures.

Retransplantation Islet Humaines Chez Un Patient Avec Diabète De Type I

Transplant International : Official Journal of the European Society for Organ Transplantation. Apr, 2002  |  Pubmed ID: 11976743

Commutateurs FLIP Fas-médiation Glucose Signalisation De L'homme Les Cellules Bêta Pancréatiques De L'apoptose à La Réplication Cellulaire

Proceedings of the National Academy of Sciences of the United States of America. Jun, 2002  |  Pubmed ID: 12060768

Diabète de type 2 résultats sucré à partir d'une adaptation insuffisante de la masse des cellules bêta pancréatiques fonctionnelles dans le visage de résistance à l'insuline. Les changements dans la concentration de glucose jouent un rôle essentiel dans la régulation du chiffre d'affaires des cellules bêta. Dans des îlots humains, les concentrations de glucose élevées nuire à la prolifération des cellules bêta et induire l'apoptose des cellules bêta par l'intermédiaire d'une régulation positive du récepteur Fas. Récemment, il a été montré que la caspase-8 FLIP inhibiteur peut détourner les signaux de mort Fas-médiation dans celles de la prolifération cellulaire dans les cellules lymphatiques. Nous avons observé expression de FLIP dans les cellules humaines pancréatiques bêta des individus non diabétiques, ce qui a été diminué dans des coupes de tissus de patients diabétiques de type 2. L'exposition in vitro d'îlots de donneurs d'organes non diabétiques à des niveaux élevés de glucose et de diminution de l'expression FLIP a augmenté le pourcentage de la borne désoxynucléotidyltransférase médiée par l'étiquetage apoptotique fin UTP (TUNEL)-positifs cellules bêta; FLIP n'était plus détectable dans ces cellules bêta TUNEL-positives. La régulation positive de la FLIP, par incubation avec transforming growth factor beta ou par transfection avec un vecteur d'expression codant pour FLIP, les protégées des cellules bêta à partir du glucose induite par l'apoptose, la prolifération des cellules beta restaurée, et l'amélioration de la fonction des cellules bêta. Les effets bénéfiques de la surexpression FLIP ont été bloqués par un antagoniste anticorps anti-Fas, en indiquant leur dépendance à l'égard l'activation du récepteur Fas. Les données actuelles fournir des preuves pour l'expression de FLIP dans la cellule bêta humaine et de proposer une nouvelle approche pour prévenir et traiter le diabète en changeant de signalisation de l'apoptose Fas à la prolifération.

La Prostaglandine E (1) Protège L'homme Des Cellules Hépatiques Sinusoïdales Endothéliales De L'apoptose Induite Par L'hypoxie Réoxygénation

Microvascular Research. Jul, 2002  |  Pubmed ID: 12074635

Hépatique d'ischémie-reperfusion est une cause importante de dysfonction du greffon après transplantation hépatique. Cellules endothéliales sinusoïdales hépatiques (LSECs) sont particulièrement sensibles à l'ischémie-reperfusion et l'apoptose. Cette étude examine le rôle protecteur de PGE (1) sur l'apoptose des LSEC pendant l'hypoxie-réoxygénation in vitro. Hypothermie-hypoxie suivie par la réoxygénation déclenché apoptose LSEC, et PGE prostaglandine (1) LSEC protégés de l'apoptose d'une manière dose-dépendante. La libération de métalloprotéases matricielles (MMP) et l'oxyde nitrique (NO) par LSECs ont augmenté après la réoxygénation hypoxie. Tant la inhibiteur de MMP BB3103 et la LNAM inhibiteur de la NO efficacement diminution de l'apoptose LSEC, suggérant un rôle distinct de MMP et de NO dans l'hypoxie-réoxygénation induite LSEC apoptose. PGE (1) régulé à la baisse la production de NO en inhibant l'expression de la NO synthase inductible dans LSEC. PGE (1) a également inhibé la MMP-2 libération de LSEC pendant la réoxygénation hypoxie. Ces résultats indiquent que la protection des LSECs de l'apoptose par la PGE (1) chez les insuffisants hépatiques d'ischémie-reperfusion est médiée par inhibitrice de NO synthase inductible et la libération de MMP.

Impact Potentiel De Fractionnement Dans Le Foie in Situ Sur Le Nombre De Greffons Disponibles

Transplantation. Jul, 2002  |  Pubmed ID: 12151735

L'augmentation potentielle du nombre de greffes du foie acquise systématiquement en utilisant la technique de fractionnement organes optimales est encore inconnue. Cette étude examine la proportion de donneurs qui doivent être pris en considération pour in situ du foie partagé la récolte selon des critères stricts sur lesquels un consensus pourrait être atteint facilement.

Réduction De La Variabilité De La Glycémie Dans Le Diabète De Type 1 Traités Par Transplantation D'îlots Pancréatiques: Intérêt De La Surveillance Du Glucose En Continu

Diabetes Care. Dec, 2002  |  Pubmed ID: 12453970

Afin de comparer les profils glycémiques des patients atteints de diabète de type 1 traités par pompe à insuline implantable ou du pancréas ou de la transplantation d'îlots par le biais du système de surveillance du glucose en continu (CGMS; Minimed, Sylmar, CA).

Hepatocellular Adenoma and Polycystic Ovary Syndrome

Liver International : Official Journal of the International Association for the Study of the Liver. Feb, 2003  |  Pubmed ID: 12640725

Various identified risk factors predispose to hepatocellular adenomas. We present the case of a young woman with liver adenoma in a context of polycystic ovary syndrome, associated with high levels of androgens and following a high dose hormonal therapy. In view of this complication, we recommend a close screening of patients with such hormonal imbalance, especially those who are treated with high doses of hormones, with repeated liver tests and ultrasonographies.

Rein-pancréas Transplantation Dans Un Long Terme Non-progresseur Infectée Par Le VIH Bénéficiaire

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. May, 2003  |  Pubmed ID: 12752321

Avec l'introduction de la thérapie antirétrovirale hautement active (HAART), l'infection à VIH est devenue une maladie chronique avec plus fréquentes défaillances d'organes en phase terminale. En conséquence, la question de la transplantation chez les patients VIH est soulevée plus souvent. Bien qu'il soit encore l'objet de controverses, l'infection à VIH n'est plus une contre-indication absolue à la transplantation d'organe solide. Nous rapportons un cas de combinés transplantation rein-pancréas chez un receveur VIH. Du VIH est restée stable, sans traitement antiviral pour un maximum de 2 ans après la transplantation et a atteint les critères pour l'inclusion dans le nonprogressor à long terme (LTNP) du groupe. Organes greffés démontré un bon fonctionnement sans rejet. Ce cas met l'accent sur la nécessité d'envisager LTNP patients atteints du VIH comme un sous-groupe spécifique, lors de l'examen de transplantation d'organe solide. Multithérapie n'est pas nécessaire, évitant ainsi les interactions médicamenteuses et de leurs caractéristiques immunologiques uniques, comme la mutation CCR5, pourrait prévenir le rejet. Ce sous-groupe de patients atteints du VIH devrait être offert un accès moins restreint à la transplantation.

Intra-portail D'injection De 400 - Microcapsules Microm Dans Un Grand Modèle-animal

Transplant International : Official Journal of the European Society for Organ Transplantation. Jun, 2003  |  Pubmed ID: 12819871

À ce jour, les greffes encapsulés ont généralement été implanté dans la cavité péritonéale. Ce site est, cependant, pas l'idéal, principalement en raison de son approvisionnement en sang. Nous avons étudié la faisabilité des échanges intra-portail injection de (400 microm) microcapsules chez le porc. Dix-mille microcapsules par kilogramme de poids corporel ont été injectés dans six porcs Large White. La pression portale, différents tests biologiques, portographies et histologie hépatique ont été enregistrées avant et à différents moments après l'injection. En conséquence, la pression portale accrue après l'injection (15 + / -2,3 vs 8,7 + / -1,7 mmHg) mais il est resté dans une fourchette acceptable (<20 mmHg) et a renvoyé à des valeurs normales à 3 mois (8,5 + / -3,7 mmHg) . Au cours du mois 3-suivi, la fonction hépatique et des tests hépatiques sont restés stables. Portographies montré une implantation homogène de la capsule, avec le flux porte toujours dirigé vers le foie. À l'examen histologique après 3 mois, les capsules ont démontré des degrés divers de la fibrose. Nous pouvons donc conclure que ces résultats démontrent que le commerce intra-portail d'injection de microcapsules est réalisable dans un grand modèle-animal. Hémodynamique, les résultats biologiques et radiologiques sont similaires à ceux observés dans les essais cliniques de libre-transplantation d'îlots.

Acquired and Reversible Pelger-Huët Anomaly of Polymorphonuclear Neutrophils in Three Transplant Patients Receiving Mycophenolate Mofetil Therapy

American Journal of Hematology. Aug, 2003  |  Pubmed ID: 12879427

Deficient nuclear segmentation and abnormal chromatin condensation define Pelger-Huët anomaly of polymorphonuclear neutrophils. Next to the hereditary irreversible form, acquired forms both reversible and irreversible have been described. We describe three transplant patients who were all investigated for a left shift in the absence of symptoms or signs of infection and in whom acquired reversible Pelger-Huët anomaly was discovered. The abnormal PMN phenotype was induced by mycophenolate mofetil (MMF). MMF is a necessary but not sufficient condition for the development of the anomaly. In our three patients a dose-response effect was observed regarding plasma MMF concentration and severity of neutrophil dysplasia. Except for one slightly elevated value, the patients' plasma MMF levels were within the therapeutic range. None of the patients, one who was neutropenic at presentation and two who were non-neutropenic, developed infectious complications. From our three cases as well as those of other authors, we identify previous graft rejection episodes as a potential predisposing factor for the development of PHA. In the first patient, drug withdrawal led to normalization of PMN morphology. In the other two patients, the left shift disappeared after dose reduction. In these latter two patients, a form of desensitization to the effect of MMF on neutro- phils was observed following re-augmentation of MMF dose.

Insulino-indépendance Après La Conversion à Tacrolimus Et Du Sirolimus Immunosuppresseur à Base De Islet-rénaux Bénéficiaires

Transplantation. Oct, 2003  |  Pubmed ID: 14557767

Activation Des Macrophages Humains Par Les Préparatifs îlots Allogéniques: Inhibition Par AOP-RANTES Et Héparinoïdes

Immunology. Apr, 2004  |  Pubmed ID: 15056378

Lors de la transplantation, les îlots pancréatiques libèrent des chimiokines qui favorisent l'attraction des macrophages, ce qui entrave la prise de greffe d'îlots. L'objectif de cette étude était de moduler la chimiotaxie et la réponse immunitaire des macrophages humains induits par des îlots. L'homme dérivées de monocytes macrophages de sujets sains ont été exposés à des surnageants d'îlots humains. Chimiotactisme, facteur de nécrose tumorale-alpha (TNF-alpha) et l'interleukine-1beta (IL-1beta) libération ont été évalués. Pour moduler la migration, les macrophages humains ont été incubées en présence de aminooxypentane-régulée sur l'activation, normal, des cellules T a exprimé, et sécrétée (AOP-RANTES), un antagoniste puissant de CCR5. Activité chimiotactique des îlots surnageant a été modulé par l'addition d'héparine ou les héparinoïdes [pentosane et calix [8S] arène (C8)]. AOP-RANTES considérablement réduit, de manière dose-dépendante, la chimiotaxie des macrophages et la libération de cytokines induite par îlots surnageant. L'indice chimiotactique a été réduit de 3,05 + / - 0,27 à 0,71 + / - 12, le TNF-alpha à partir de 1205 + / - 52 à 202 + / - 12 pg / ml, et de l'IL-1beta à partir de 234 + / - 12 à 10 + / - 6 pg / ml. Le piégeage des chimiokines par héparinoïdes réduit l'activité chimiotactique des îlots surnageant de 3,05 + / - 0,27 à 1,2 + / - 0,1 avec de l'héparine ou de pentosan et à 1,72 + / - 0,22, C8, et a également diminué la libération de TNF-alpha par les macrophages humains à partir de 1205 + / - 35 à 1000 + / - 26 (C8), 250 + / - 21 (héparine) et 320 + / - 19 (pentosane) pg / ml, et de l'IL-1beta à partir de 234 + / - 13 à 151 + / - 5 (C8), 50 + / - 3 (héparine) et 57 + / - 4 (pentosane) pg / ml. En conclusion, l'AOP-RANTES et héparinoïdes inhiber l'activation des macrophages humains et les migrations induites par îlots surnageant.

Les Critères Pour Les Donneurs De Pancréas Et D'îlots De Langerhans Suffisamment Différentes Pour Réduire La Concurrence?

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. May, 2004  |  Pubmed ID: 15084172

La greffe d&#39;îlots du pancréas et peut concourir pour un nombre limité d&#39;organes. Nous avons analysé les dossiers à partir du Registre national suisse de transplantation au cours d&#39;une période de 4 ans afin d&#39;étudier la proportion de donneurs qui sont appropriés pour l&#39;îlot et de la transplantation du pancréas. Aptitude à la transplantation du pancréas a été principalement défini comme suit: âge 10-45 ans; poids <or= 80 kg; BMI <or= 25 kg/m(2); amylasemia <or= 150 U/l; ICU stay <or= 3 days and absence of severe hypotension (MAP <or= 60 mmHG). Between 1.1.1997 and 31.12.2000, data of 407 donors were collected, from which 321 donors were included in the study. Thirty-three (10%), 143 (45%), and 23 (7%) donors fulfilled the criteria for pancreas, islet transplantation, and both procedures, respectively. Giving priority to pancreas transplantation and accepting the absence of one selection criterion, 90 (28%) pancreas and 100 (31%) islet donors were identified. We conclude that with current allocation policies prioritizing pancreas transplantation, pancreas and islet transplantation may coexist with little competition.

Positron-emission Tomography Imaging of Early Events After Transplantation of Islets of Langerhans

Transplantation. Feb, 2005  |  Pubmed ID: 15699768

The aim of our study was to assess cell trafficking and early events after intraportal islet transplantation. Sprague-Dawley rat islets were incubated for various times, with various concentrations of 2-[F]fluoro-2deoxy-D-glucose (FDG), and in presence of various glucose concentrations. FDG-labeled syngeneic islets or FDG alone were injected in rats. Radioactivity was measured in the liver and in various organs by positron-emission tomography for 6 hours. FDG uptake increased with incubation time or FDG concentration and decreased in presence of glucose. In vivo, all islets implanted in the liver, with an uptake 4.4 times higher than controls (44.2% vs. 10.1%, P=0.02). Radioactivity in the liver decreased at the same rate after injection of labeled-islets and FDG alone. Ex vivo labeling of islets and imaging of posttransplant early events were feasible. Islets engrafted exclusively in the liver. No islet loss could be demonstrated 6 hours after transplantation.

Intussusception As a Cause of Bowel Obstruction in Adults

Swiss Medical Weekly. Feb, 2005  |  Pubmed ID: 15729613

Due to its unspecific presentation, intussusception is often diagnosed with delay in adults.

L&#39;épuisement Des Macrophages Prolonge Discordante, Mais Ne Concordent Pas La Survie Des Xénogreffes Islet

Transplantation. Mar, 2005  |  Pubmed ID: 15753843

Cellules T et les macrophages jouent un rôle majeur dans le rejet des îlots xénogreffées. Selon la disparité phylogénétique, présentation de l&#39;antigène directe ou indirecte est prédominante. Le but de cette étude était d&#39;analyser in vitro de la prédominance de la présentation directe ou indirecte en appauvrissant cellules présentatrices d&#39;antigène dans concordant et discordant combinaisons xénogéniques. In vivo, nous avons analysé l&#39;effet de l&#39;épuisement des macrophages sur la survie des îlots xénogreffe concordante et discordante à évaluer dans quelle combinaison de cette stratégie peut être utilisée comme outil thérapeutique.

Impact of HLA Matching on the Outcome of Simultaneous Pancreas-kidney Transplantation

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. May, 2005  |  Pubmed ID: 15814550

Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of human leukocyte antigen (HLA) matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study.

Surveillance Microbienne Lors De L&#39;isolement Des îlots Pancréatiques Humaines

Transplant International : Official Journal of the European Society for Organ Transplantation. May, 2005  |  Pubmed ID: 15819808

L&#39;objectif de cette étude était d&#39;enquêter sur le taux de contamination microbiologique lors de l&#39;isolement des îlots pancréatiques humains. Entre 1996 et 2002, les médias de préservation du pancréas et préparations d&#39;îlots post-purification ont été testés pour la contamination microbiologique. Après l&#39;arrivée dans le laboratoire, pancréas ont été lavées avant la perfusion enzymatique avec une solution soit saline équilibrée de Hank (Groupe I, n = 170, de 1996 à 2001) ou décontaminés avec polyvidonum-iode, céfazoline, et amphotéricine B (Groupe II, n = 45 , de 2001 à 2002). La contamination microbiologique des milieux de conservation a été observée dans 56% et 84% pour les groupes I et II, respectivement. Analyse de contaminants révélé 74% à Gram positif, 21% bactéries Gram-négatives et les champignons 5%. Durée de transport ont eu une influence sur le taux de contamination (P &lt;0,05). Après isolement des îlots, Groupe I a présenté la contamination microbienne des 16 préparations d&#39;îlots (9,4%) [c.-à-bactéries Gram-positives (n = 10), bactéries à Gram négatif (n = 4), et les champignons (n ​​= 2)]. Dans le groupe II, à seulement 2 préparations d&#39;îlots (4,4%) ont présenté une contamination microbienne. La contamination microbienne au cours de l&#39;approvisionnement du pancréas se produit fréquemment. La plupart des micro-organismes sont éliminés lors de l&#39;isolement des îlots, et De contaminations au cours de novo d&#39;isolement des îlots sont rares. La décontamination du pancréas diminue le risque d&#39;infection de la préparation des îlots finale.

Logistics and Transplant Coordination Activity in the GRAGIL Swiss-French Multicenter Network of Islet Transplantation

Transplantation. May, 2005  |  Pubmed ID: 15880070

Since the Edmonton trial in 2000, increasing numbers of transplant centers have been implementing islet transplantation programs. Some institutions have elected to associate in multicenter networks, such as the Swiss-French GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d'Ilots de Langerhans) consortium.

Effet De La Composition De Microcapsules Et à Court Terme Sur La Biocompatibilité Immunosuppression Intraportale

Cell Transplantation. 2005  |  Pubmed ID: 15881425

Avec plus de nutriments et d&#39;oxygène et un contact étroit avec le sang, la veine porte est une alternative possible à la cavité péritonéale pour la transplantation de cellules encapsulées. Les données concernant la biocompatibilité intraportale de microcapsules font défaut. Microcapsules ont été compilés à partir de cinq types d&#39;alginate se différenciant par leur masse molaire et mannuronique / guluronique rapports des acides par formation de complexes avec les cations divalents (baryum ou de calcium) ou des mélanges de cations divalents et des polycations. Ils ont été injectés dans la veine porte de rats, et cellulaire et fibreuse d&#39;épaisseur a été mesurée infiltration pericapsular 3 et 7 jours après l&#39;implantation. Prolifération a été caractérisée par différentes colorations ou immunohistochimie (hématoxyline et l&#39;éosine, Giemsa, ED-1 pour des monocytes / macrophages, l&#39;alpha-actine pour myofibroblastes, CD31 pour les cellules endothéliales). L&#39;impact de court terme immunosuppression (chlorure de gadolinium IV 20 mg / kg / jour les jours - 1 et 4 ainsi que les 10 jours de la rapamycine PO 1 mg / kg / jour, le tacrolimus PO 3 mg / kg / jour, ou des combinaisons de la rapamycine / tacrolimus ou de gadolinium / tacrolimus) a en outre été évalué 3, 7 et 42 jours après l&#39;implantation. Dans l&#39;ensemble, la prolifération a augmenté de jour 3 au jour 7 (p &lt;0,05). Trois et sept jours après l&#39;implantation, polycation contenant des microcapsules a induit plus de réaction que les microbilles (p &lt;0,0001 et p &lt;0,01). Considérant polycation-libres perles, de baryum-alginate induit la plus faible réaction. Biocompatibilité des microbilles était indépendante de la proportion d&#39;acide mannuronique / guluronique et la masse molaire de l&#39;alginate. Infiltration est principalement une réaction à corps monocytes / macrophages riche étrangère, mais une réaction immuno-allergique contenant des éosinophiles a également été observée. À court terme immunosuppression considérablement réduit l&#39;infiltration dans toutes les conditions et jusqu&#39;à 42 jours après l&#39;implantation. Biocompatibilité après intraportale perfusion était le meilleur pour le baryum-alginate microbilles les plus pauvres et pour polycation contenant des microcapsules. Prolifération à court et à long terme pourrait être considérablement réduite par une immunosuppression à court terme.

Islet Transplantation in a Recipient Presenting the Factor V Leiden Mutation

Transplantation. Jun, 2005  |  Pubmed ID: 15973190

Expression and Secretion of Alpha1-proteinase Inhibitor Are Regulated by Proinflammatory Cytokines in Human Pancreatic Islet Cells

Diabetologia. Aug, 2005  |  Pubmed ID: 16001235

Alpha1-proteinase inhibitor (alpha1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of alpha1-PI is the liver, but other tissues, including pancreatic islets, also synthesise this molecule. The aims of this study were to assess the islet cell types that produce alpha1-PI, to determine whether alpha1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated.

Traitement D'une Insuffisance Hépatique Fulminante Par Transplantation De Microencapsulés Hépatocytes Xénogéniques Primaires Ou Immortalisées

Xenotransplantation. Nov, 2005  |  Pubmed ID: 16202069

Le but de cette étude était d'évaluer les fonctions in vitro et in vivo d'hépatocytes isolés après l'immortalisation, cryoconservation, encapsulation et xénotransplantation dans des souris présentant une insuffisance hépatique fulminante (FLF).

Impairment of Renal Function After Islet Transplant Alone or Islet-after-kidney Transplantation Using a Sirolimus/tacrolimus-based Immunosuppressive Regimen

Transplant International : Official Journal of the European Society for Organ Transplantation. Nov, 2005  |  Pubmed ID: 16221151

The immunosuppressive (IS) regimen based on sirolimus/low-dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low-dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6 months follow up were reviewed. There were five islet-after-kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long-established kidney graft were associated with poorer outcome.

Management of Hepatocellular Adenoma: Solitary-uncomplicated, Multiple and Ruptured Tumors

World Journal of Gastroenterology : WJG. Sep, 2005  |  Pubmed ID: 16237767

While hepatocellular adenomas (HAs) have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs.

Does Mycophenolate Mofetil Reduce the Risk of Late Acute Rejection After Liver Transplantation?

Nature Clinical Practice. Gastroenterology & Hepatology. Dec, 2006  |  Pubmed ID: 17130874

De Novo Sirolimus Immunosuppresseur à Base Après Transplantation Hépatique Pour Carcinome Hépatocellulaire: Résultats à Long Terme Et Effets Secondaires

Transplantation. May, 2007  |  Pubmed ID: 17496530

Nous rapportons les résultats à long terme et les effets secondaires après la transplantation pour carcinome hépatocellulaire (CHC) à l&#39;aide de novo, le sirolimus basée sur l&#39;immunosuppression (IS).

Transplantation Du Foie ABO-incompatible Pour Les Patients Adultes Gravement Malades

Transplant International : Official Journal of the European Society for Organ Transplantation. Aug, 2007  |  Pubmed ID: 17521384

ABO incompatibles transplantation du foie (ABO-In) reste une solution controversée à une insuffisance hépatique aiguë chez les adultes. Bénéficiaires du foie adultes atteints d&#39;insuffisance hépatique aiguë ou gravement décompensée fin stade de la maladie, intubé et / ou dans l&#39;unité de soins intensifs, ont été regroupés comme ABO-In (n = 14), ABO compatible (n = 29, ABO-C) et ABO-identique (n = 65, ABO-Id). ABO-en immunosuppression quadruple reçu avec des agents d&#39;induction d&#39;anticorps qui appauvrissent (sauf deux), les inhibiteurs de la calcineurine, antimétabolites et des stéroïdes. Aucune différence significative de survie des patients et des greffons a été observée chez ABO-In, ABO et ABO-C-Id: survivances de greffe était de 64%, 62% et 67%, respectivement, en 1 an et 56%, 54% et 60%, respectivement, en 5 ans; survivances des patients 86%, 69% et 67%, respectivement, en 1 an et 77%, 61% et 62%, respectivement, dans les 5 ans. Trois ABO dans les greffes ont été perdus (un hyper-rejet aigu et deux thrombose de l&#39;artère hépatique). Les complications chirurgicales et infectieuses étaient également distribués entre les groupes, à l&#39;exception de la thrombose de l&#39;artère hépatique, plus fréquentes dans le système ABO Dans (2, 14%) que ABO-I (1, 1,5%, P &lt;0,05). Contrairement aux études précédentes, aucune différence significative de survie des patients et des greffons a pu être observée parmi tous les paramètres de compatibilité ABO. Nos résultats suggèrent que le système ABO incompatibles greffes devrait être considérée comme une option thérapeutique importante chez les patients adultes atteints d&#39;insuffisance hépatique aiguë en attente d&#39;une procédure d&#39;urgence.

Quality of Life After Islet Transplant: Impact of the Number of Islet Infusions and Metabolic Outcome

Transplantation. Sep, 2007  |  Pubmed ID: 17876283

The health-related quality of life (HRQL; Health Utilities Index Mark 2) and the fear of hypoglycemia (Hypoglycemia Fear Survey) were assessed after islet transplant; the impact of a single islet infusion and of the metabolic outcome were determined. A control group included 166 patients with type 1 diabetes. Islet transplant had no impact on overall HRQL. Prior to transplant, islet recipients had more fear of hypoglycemia than controls (P<0.000001), but this improved up to 36 months after transplant (P<0.00001, pretransplant vs. each time point). With a single islet infusion, this fear improved substantially (P<0.00001), but improved further with subsequent islet infusions (P

The Caspase Selective Inhibitor EP1013 Augments Human Islet Graft Function and Longevity in Marginal Mass Islet Transplantation in Mice

Diabetes. Jun, 2008  |  Pubmed ID: 18356409

Clinical islet transplantation can provide insulin independence in patients with type 1 diabetes, but chronic graft failure has been observed. This has been attributed in part to loss of >or=60% of the transplanted islets in the peritransplant period, resulting in a marginal implant mass. Strategies designed to maximize survival of the initial islet mass are likely to have major impact in enhancing long-term clinical outcomes. EP1013 (N-benzyloxycabonyl-Val Asp-fluoromethyl ketone [zVD-FMK]), is a broad-spectrum caspase selective inhibitor with no observed toxicity in rodents.

Volume Total De La Tumeur Prédit Le Risque De La Transplantation Hépatique Chez Les Patients De Récurrence Suivante Atteints De Carcinome Hépatocellulaire

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Aug, 2008  |  Pubmed ID: 18668667

Critères de sélection des candidats à une transplantation du foie dans la présence d&#39;un carcinome hépatocellulaire (CHC) devrait prédire avec précision récidive post-transplantation tout en n&#39;excluant pas un nombre excessif de patients de poser leur candidature. Critères existants sont remis en cause par la précision limitée de l&#39;évaluation radiologique. Le volume total de la tumeur (VTT) a été calculé par l&#39;addition du volume de chaque tumeur individuelle. Une analyse préliminaire a été réalisée sur les données des patients HCC du Programme de transplantation hépatique de l&#39;Alberta (52 patients) et ensuite validés sur des populations des universités de Toronto et au Colorado programmes (154 et 82 patients). Une coupure TTV de 115 cm (3) a été choisi sur la base du risque de récidive avec l&#39;utilisation d&#39;une courbe caractéristique de fonctionnement du récepteur. Radiologie en corrélation plus étroite à la pathologie avec TTV qu&#39;avec Milan et l&#39;Université de Californie à San Francisco (UCSF) critères (91% contre 69% et 75% des patients, p &lt;0,0001). Bien que plus de patients répondaient aux critères de qualification pour la transplantation avec TTV (28% -53% de plus que Milan et 16% -26% de plus que l&#39;UCSF), aucune détérioration du résultat a été démontré dans une analyse des patients au sein de TTV &lt;ou = 115 cm (3 ) en comparaison avec ces classifications Milan ou UCSF réunion de tous les établissements. Les patients atteints de TTV&gt; 115 cm (3) a connu plus de récidives et la survie des patients dans le bas de l&#39;Alberta et le Colorado série (P &lt;0,05). Lorsque TTV avec une coupure de 115 cm (3) est utilisé pour la sélection des candidats, la précision de l&#39;évaluation radiologique avant la transplantation est rehaussée, avec des résultats transplantés pas différents de ceux obtenus avec les classifications de Milan et de l&#39;UCSF, malgré une population de patients plus inclusive.

The Role of Macrophage Migration Inhibitory Factor in Mouse Islet Transplantation

Transplantation. Nov, 2008  |  Pubmed ID: 19034004

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by many tissues including pancreatic beta-cells.

Porcine Marginal Mass Islet Autografts Resist Metabolic Failure over Time and Are Enhanced by Early Treatment with Liraglutide

Endocrinology. May, 2009  |  Pubmed ID: 19131571

Although insulin independence is maintained in most islet recipients at 1 yr after transplant, extended follow-up has revealed that many patients will eventually require insulin therapy. Previous studies have shown that islet autografts are prone to chronic failure in large animals and humans, suggesting that nonimmunological events contribute to islet graft functional decay. Early intervention with therapies that promote graft stability should provide a measurable benefit over time. In this study, the efficacy of the long-acting glucagon-like peptide-1 analog liraglutide was explored in a porcine marginal mass islet autograft transplant model. Incubation with liraglutide enhanced porcine islet survival and function after prolonged culture. Most vehicle-treated (83%) and liraglutide-treated (80%) animals became insulin independent after islet autotransplantation. Although liraglutide therapy did not improve insulin independence rates or blood glucose levels after transplant, a significant increase in insulin secretion and acute-phase insulin response was observed in treated animals. Surprisingly, no evidence for deterioration of graft function was observed in any of the transplanted animals over more than 18 months of follow-up despite significant weight gain; in fact, an enhanced response to glucose developed over time even in control animals. Histological analysis showed that intraportally transplanted islets remained highly insulin positive, retained alpha-cells, and did not form amyloid deposits. This study demonstrates that marginal mass porcine islet autografts have stable long-term function, even in the presence of an increasing metabolic demand. These results are discrepant with previous large animal studies and suggest that porcine islets may be resistant to metabolic failure.

Protein Kinase C Inhibitor, AEB-071, Acts Complementarily with Cyclosporine to Prevent Islet Rejection in Rats

Transplantation. Jan, 2009  |  Pubmed ID: 19136892

AEB-071 (AEB) is a specific inhibitor of protein kinase C, which prevents T-lymphocyte activation. The present study investigated the effect of AEB on rat islet allotransplantation alone or in combination with CTLA4-Ig, mycophenolate mofetil, or cyclosporine A (CsA).

Réévaluer Les Critères De Sélection Avant De Transplantation Hépatique Pour Carcinome Hépatocellulaire Utilisant Le Registre Scientifique De Receveurs De Greffes De Base De Données

Hepatology (Baltimore, Md.). Mar, 2009  |  Pubmed ID: 19152426

Le modèle actuel d&#39;attribution des greffons hépatiques en place aux États-Unis favorise la transplantation des patients atteints de carcinomes hépatocellulaires (CHC petits) dans les critères de Milan (une tumeur unique jusqu&#39;à 5 cm de diamètre ou jusqu&#39;à trois lésions, aucun supérieur à 3 cm) . Bien que plusieurs rapports ont suggéré que ces critères pourrait être étendu, il n&#39;existe actuellement aucun accord sur les outils de sélection de nouvelles. Dans cette étude, nous avons effectué une vue d&#39;ensemble de 6478 bénéficiaires adultes d&#39;une première greffe de foie isolé inscrit dans le Registre scientifique de receveurs d&#39;une transplantation (SRTR) base de données. De Mars 2002 à Janvier 2008, un nombre croissant de patients en dehors de Milan critères (P <or= 0.001) have been registered for a transplant, but they still represent less than 5% of the transplants performed for HCC. Of all the tested variables (tumor number, largest tumor size, and Milan and University of California San Francisco criteria), only total tumor volume (TTV; P <or= 0.05) and alpha fetoprotein (AFP; P <or= 0.001) could predict patient survival. While these two parameters demonstrated independent behaviors (no patient demonstrated an increase in both values), a composite score was defined, with patients with a TTV > 115 cm (3) ou une AFP&gt; 400 ng / mL étant critères extérieurs. Le combiné TTV / AFP score de survie post-transplantation efficacement prédit (rapport de risque = 2, intervalle de confiance à 95% = 1.7 à 2.4, P <or= 0.001); patients not meeting these criteria had a survival below 50% at 3 years. Conclusion: According to the present SRTR data, Milan criteria are too restrictive, and patients with larger TTV can enjoy satisfactory posttransplant survivals. A composite patient selection score combining TTV and AFP was the most effective of all tested staging criteria for the prediction of posttransplant patient survival for candidates with HCC.

Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD Mice

Diabetes. Jun, 2009  |  Pubmed ID: 19289457

The T helper 17 (Th17) population, a subset of CD4-positive T-cells that secrete interleukin (IL)-17, has been implicated in autoimmune diseases, including multiple sclerosis and lupus. Therapeutic agents that target the Th17 effector molecule IL-17 or directly inhibit the Th17 population (IL-25) have shown promise in animal models of autoimmunity. The role of Th17 cells in type 1 diabetes has been less clear. The effect of neutralizing anti-IL-17 and recombinant IL-25 on the development of diabetes in NOD mice, a model of spontaneous autoimmune diabetes, was investigated in this study.

Le Nombre Estimé De Patients Atteints De Carcinome Hépatocellulaire Sélectionné Pour La Transplantation Du Foie En Fonction De Critères De Sélection élargis

Transplant International : Official Journal of the European Society for Organ Transplantation. Sep, 2009  |  Pubmed ID: 19386075

Récemment, plusieurs groupes ont introduit des critères élargis pour la sélection des patients atteints de carcinome hépatocellulaire (CHC) avant la greffe, mais le nombre exact de patients potentiels nouvellement recrutés reste incertaine. Cette étude basée sur le Registre évalué 270 patients diagnostiqués avec un CHC. Le nombre potentiel de candidats à la transplantation a été fondée sur l&#39;âge (&lt;ou = 65 ans), absence de métastases et macro-vasculaires invasion, et le 12 déjà parus, les critères de sélection élargis. Un large éventail d&#39;augmentation du nombre de candidats à la transplantation a été observée (de 12 à 63% lorsque comparé avec le nombre de ces candidats qui ont été sélectionnés uniquement sur la base des critères de Milan). Les critères les plus conservatrices étaient Séoul (Kwon, 2007; augmentation de 12%), Valence (Silva, 2008; 16%), le total des tumeurs de volume / alpha-foetoprotéine (Toso, 2009; 20%) et de l&#39;UCSF (Yao, 2007, 20 %). Ces données aideront centres et organismes de la politique dans la prévision de la nécessité pour les ressources liées à un élargissement des critères d&#39;.

Costimulatory Blockade with Belatacept in Clinical and Experimental Transplantation - a Review

Expert Opinion on Biological Therapy. Jun, 2009  |  Pubmed ID: 19426116

Current maintenance immunosuppression agents have been critical to the improved graft and patient survival rates in solid organ transplantation observed over the past decade. However, long-term follow-up has revealed that these agents are associated with troublesome side effects and chronic toxicity, contributing to graft loss and death.

Immunomodulation by Blockade of the TRANCE Co-stimulatory Pathway in Murine Allogeneic Islet Transplantation

Transplant International : Official Journal of the European Society for Organ Transplantation. Sep, 2009  |  Pubmed ID: 19453995

We explore herein the effect of TNF-related activation-induced cytokine (TRANCE) co-stimulatory pathway blockade on islet survival after allograft transplantation. Expression of TRANCE on murine C57Bl/6 (B6) CD4+ T cells after allogeneic activation was analyzed by fluorescence-activated cell sorter (FACS). The effect of a TRANCE receptor fusion protein (TR-Fc) and anti-CD154 antibody (MR1) on B6 spleen cell proliferation after allogeneic activation was assessed by mixed lymphocyte reaction (MLR). Three groups of B6 mice were transplanted with allogeneic islets (DBA2): Control; short-term TR-Fc-treatment (days 0-4); and prolonged TR-Fc-treatment (days -1 to 13). Donor-specific transfusion (DST) was performed at the time of islet transplantation in one independent experiment. Transplantectomy samples were analyzed by immunohistochemistry. TRANCE expression was upregulated in stimulated CD4+ T cells in vitro. In MLR experiments, TR-Fc and MR1 both reduced spleen cell proliferation, but less than the combination of both molecules. Short-course TR-Fc treatment did not prolong islet graft survival when compared with controls (10.6 +/- 1.9 vs. 10.7 +/- 1.5 days) in contrast to prolonged treatment (20.7 +/- 3.2 days; P < 0.05). After DST, primary non function (PNF) was observed in half of control mice, but never in TR-Fc-treated mice. Immunofluorescence staining for Mac-1 showed a clear decrease in macrophage recruitment in the treated groups. TRANCE-targeting may be an effective strategy for the prolongation of allogeneic islet graft survival, thanks to its inhibitory effects on co-stimulatory signals and macrophage recruitment.

Histologic Graft Assessment After Clinical Islet Transplantation

Transplantation. Dec, 2009  |  Pubmed ID: 19996928

An accurate monitoring would help understanding the fate of islet grafts after transplantation.

Effect of Different Induction Strategies on Effector, Regulatory and Memory Lymphocyte Sub-populations in Clinical Islet Transplantation

Transplant International : Official Journal of the European Society for Organ Transplantation. Feb, 2009  |  Pubmed ID: 18713144

This prospective study assessed lymphocyte subsets in the peripheral blood of 42 islet allograft recipients using flow cytometry from 2 weeks and up to 2 years post-transplantation. Subjects received daclizumab (n = 16), Thymoglobulin (n = 12) or alemtuzumab (n = 14). Alemtuzumab was associated with an early (within 1 month) and transient (up to 6 months) increase in the frequency of CD3(+) CD4(+) Foxp3(+) T cells, while daclizumab induced a near complete loss of these cells (P

In Vivo Study of HCV in Mice with Chimeric Human Livers

Methods in Molecular Biology (Clifton, N.J.). 2009  |  Pubmed ID: 19009277

Estimates of hepatitis C virus infection include 170 million people worldwide, who face increased risk of development of cirrhosis, liver failure, and hepatocellular carcinoma. Standard of care therapy with pegylated interferon and ribavirin is effective in just half of patients, is challenged by substantial treatment-related morbidity, and is prohibitively expensive in most parts of the world. New therapeutics for treatment and prevention are clearly needed. Development of effective therapies has been significantly hampered by difficulties in establishing in vitro and in vivo models of viral replication. This chapter reviews development, validation, and early application of a mouse model with a chimeric human liver.

L&#39;impact De Sirolimus Sur La Prolifération Des Hépatocytes Après Transplantation Donneur De Foie Habitable

Clinical Transplantation. Sep-Oct, 2010  |  Pubmed ID: 20002466

Il ya un manque de données sur l&#39;utilisation du sirolimus après transplantation hépatique partielle, en particulier quant à son impact sur la régénération post-transplantation.

Vascular Endothelial Growth Factor Expression in Hepatic Epithelioid Hemangioendothelioma: Implications for Treatment and Surgical Management

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Feb, 2010  |  Pubmed ID: 20104492

Epithelioid hemangioendothelioma (EHE) is a low-grade, malignant vascular tumor that most commonly presents within the liver. Patients with hepatic EHE are often candidates for liver transplantation as the disease is usually multifocal at diagnosis. Although these patients achieve excellent early outcomes post-transplant, there are very few data regarding tumor markers that can further direct chemotherapy in hepatic EHE to prevent recurrent disease. The purpose of this study was to analyze the expression of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors in hepatic EHE. Six patients with hepatic EHE were assessed for liver transplantation at our center. Pathology specimens of primary and recurrent EHE were analyzed by hematoxylin and eosin staining and by immunofluorescence for VEGF, fetal liver kinase 1 (Flk-1), and fms-related tyrosine kinase 1 (Flt-1) expression. Five patients underwent liver transplantation, and 1 patient underwent liver resection. Biopsy-proven recurrent EHE occurred in 3 patients. VEGF expression was present in 100% of the EHE specimens examined, whereas Flt-1 expression was present in only 1 sample, and Flk-1 was not observed in any of the specimens. In 1 patient with recurrent hepatic EHE post-liver transplantation, a progressive increase in the VEGF fluorescence intensity and distribution was observed. In conclusion, in this series, VEGF expression was observed in all hepatic EHE specimens analyzed. These data suggest that anti-VEGF chemotherapeutic agents will be of use in patients with hepatic EHE, particularly as a means of reducing the tumor volume prior to resection, as a means of treating unresectable or metastatic disease, or as an adjuvant therapy in the setting of liver transplantation.

Supplemental Islet Infusions Restore Insulin Independence After Graft Dysfunction in Islet Transplant Recipients

Transplantation. Feb, 2010  |  Pubmed ID: 20145529

The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide.

Insulin-heparin Infusions Peritransplant Substantially Improve Single-donor Clinical Islet Transplant Success

Transplantation. Feb, 2010  |  Pubmed ID: 20177350

Successful islet transplantation can result in insulin independence in many patients with type 1 diabetes mellitus, but it often requires more than one islet infusion. The ability to achieve insulin independence with a single donor is an important goal in clinical islet transplantation due to the limited organ supply.

Le Sirolimus Est Basée Sur L&#39;immunosuppression Associée à Une Survie Accrue Après Transplantation Hépatique Pour Carcinome Hépatocellulaire

Hepatology (Baltimore, Md.). Apr, 2010  |  Pubmed ID: 20187107

La transplantation hépatique est une option thérapeutique importante pour les patients sélectionnés atteints de carcinome hépatocellulaire non résécable (HCC). Plusieurs rapports ont suggéré un risque moindre de récidive de la tumeur après la greffe avec l&#39;utilisation du sirolimus et un autre plus élevé avec inhibiteurs de la calcineurine, mais la sélection d&#39;un protocole immunosuppresseur idéal est encore un sujet de débat. Le but de cette étude était de définir l&#39;immunosuppression associée à la meilleure survie après transplantation hépatique pour carcinome hépatocellulaire. Il a été basé sur le registre scientifique de greffés et inclus 2.491 receveurs adultes de transplantation hépatique pour carcinome hépatocellulaire isolé et 12,167 pour les non-HCC diagnostics entre Mars 2002 et Mars 2009. Tous les patients sont restés stables sur protocoles d&#39;immunosuppression d&#39;entretien pour au moins 6 mois transplantés. Dans une analyse multivariée, seul un traitement d&#39;entretien anti-CD25 induction d&#39;anticorps et de sirolimus à base ont été associés à l&#39;amélioration des survivances après la transplantation pour carcinome hépatocellulaire (rapport de risque relatif [RR] 0,64, intervalle de confiance à 95% [IC]: 0,45 à 0,9, P &lt;ou = 0,01; HR 0,53, IC 95%: de 0,31 à 0.92, P &lt;ou = 0,05, respectivement). Les autres médicaments étudiés, y compris les inhibiteurs de la calcineurine, n&#39;ont pas démontré un impact significatif. Dans un effort pour comprendre si les effets observés étaient dus à un impact direct du médicament sur la tumeur ou plus sur la greffe de foie en général, nous avons effectué une analyse similaire sur la non-HCC patients. Bien que l&#39;induction anti-CD25 a été de nouveau associée à une tendance vers une amélioration de la survie, le sirolimus a montré une tendance à la baisse des taux de survie en situation de non-HCC bénéficiaires, ce qui confirme la spécificité de son impact bénéfique pour les patients atteints de cancer. Conclusion: D&#39;après ces données, le sirolimus immunosuppresseur à base a des effets transplantés sur des patients HCC uniques qui conduisent à une meilleure survie.

Role of Imaging in Clinical Islet Transplantation

Radiographics : a Review Publication of the Radiological Society of North America, Inc. Mar, 2010  |  Pubmed ID: 20228322

Islet transplantation is an innovative and effective clinical strategy for patients with type 1 diabetes whose clinical condition is inadequately managed even with the most aggressive medical treatment regimens. In islet transplantation, purified islets extracted from the pancreas of deceased donors are infused into the portal vein of the recipient liver. Engrafted islets produce insulin and thus restore euglycemia in many patients. After islet transplantation performed with the original Edmonton protocol, 80% of patients were insulin independent at 1 year and approximately 20% were insulin independent at 5 years. With more recent technical advances, 50% of patients or more maintain insulin independence 5 years after islet transplantation. The success rate with single-donor islet infusions has markedly improved over time. Even in patients who lose insulin independence, islet transplantation is considered successful because it provides improved glycemic control and a higher quality of life. Imaging plays an important role in islet transplantation and is routinely used to evaluate potential recipients, guide the transplantation process, and monitor patients for posttransplantation complications. Because of the success of islet transplantation and its increasing availability worldwide, familiarity with the role of imaging is important.

Caspase Inhibitor Therapy Synergizes with Costimulation Blockade to Promote Indefinite Islet Allograft Survival

Diabetes. Jun, 2010  |  Pubmed ID: 20332344

Costimulation blockade has emerged as a selective nontoxic maintenance therapy in transplantation. However, these drugs must be combined with other immunomodulatory agents to ensure long-term graft survival.

The Place of Downstaging for Hepatocellular Carcinoma

Journal of Hepatology. Jun, 2010  |  Pubmed ID: 20385428

In the treatment of hepatocellular carcinomas, therapies such as trans-arterial chemo-embolisation, trans-arterial radioembolisation, percutaneous ethanol injection and radio-frequency ablation can decrease the size (and overall viability) of the tumours, thus potentially increasing the proportion of patients qualifying for resection and transplantation. While the use of such downstaging therapies is straightforward when resection is the aim, in a similar way to other neo-adjuvant treatments in the surgery of tumours that are too large or awkwardly placed to be primarily resected the issues related to transplantation are more complex. In the context of transplantation the word "downstaging" designates not only a neo-adjuvant treatment, but also a selection strategy to allow patients who are initially outside accepted listing criteria to benefit from transplantation should the neo-adjuvant therapy be successful in reducing tumour burden. The effectiveness of downstaging as a selection strategy, at first questioned because of methodological bias in the studies that described it, has been recently demonstrated by more solid prospective investigations. Several issues however remain open, such as inclusion criteria before the strategy is implemented (size/number, surrogate markers of differentiation/vascular invasion such as alpha-fetoprotein), the choice of which downstaging therapy, the end-points of treatment, and the need and duration of a period of observation proving disease response or stabilisation before the patient can be listed. The present review discusses which treatments and strategies are available for downstaging HCC on the basis of the published literature.

Calcifying Bowel Inflammation: a Case Report

Gastroenterology Research and Practice. 2010  |  Pubmed ID: 20490272

We report about a previously healthy 72-year-old woman, presented with 6 days of left lower quadrant abdominal pain and constipation. There was no report of fever, melena, hematochezia or change in appetite. The physical exam demonstrated a distended abdomen with palpable left lower quadrant pain, without guarding. CT showed images compatible with a sigmoid diverticulitis and a calcification of the sigmoid colon. After antibiotic threatment, a colonoscopy was performed which revealed the presence of a shell in the sigmoid colon. Our case illustrates the need for a colonoscopy following an attack of diverticulitis to look for a cancer or rarely a foreign body.

Macrophage Migration Inhibitory Factor Deficiency Leads to Age-dependent Impairment of Glucose Homeostasis in Mice

The Journal of Endocrinology. Sep, 2010  |  Pubmed ID: 20566490

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by many cells and tissues including pancreatic beta-cells, liver, skeletal muscle, and adipocytes. This study investigates the potential role of MIF in carbohydrate homeostasis in a physiological setting outside of severe inflammation, utilizing Mif knockout (MIF-/-) mice. Compared with wild-type (WT) mice, MIF-/- mice had a lower body weight, from birth until 4 months of age, but subsequently gained weight faster, resulting in a higher body weight at 12 months of age. The lower weight in young mice was related to a higher energy expenditure, and the higher weight in older mice was related to an increased food intake and a higher fat mass. Fasting blood insulin level was higher in MIF-/- mice compared with WT mice at any age. After i.p. glucose injection, the elevation of blood insulin level was higher in MIF-/- mice compared with WT mice, at 2 months of age, but was lower in 12-month-old MIF-/- mice. As a result, the glucose clearance during intraperitoneal glucose tolerance tests was higher in MIF-/- mice compared with WT mice until 4 months of age, and was lower in 12-month-old MIF-/- mice. Insulin resistance was estimated (euglycemic-hyperinsulinemic clamp tests), and the phosphorylation activity of AKT was similar in MIF-/- mice and WT mice. In conclusion, this mouse model provides evidence for the role of MIF in the control of glucose homeostasis.

Factors Affecting Hepatocyte Isolation, Engraftment, and Replication in an in Vivo Model

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Aug, 2010  |  Pubmed ID: 20677288

Human hepatocyte transplantation is an alternative treatment for acute liver failure and liver diseases involving enzyme deficiencies. Although it has been successfully applied in selected recipients, both isolation and transplantation outcomes have the potential to be improved by better donor selection. This study assessed the impact of various donor variables on isolation outcomes (yield and viability) and posttransplant engraftment, using the SCID/Alb-uPA (severe combined immunodeficient/urokinase type plasminogen activator under the control of an albumin promoter) human liver chimeric mouse model. Human hepatocytes were obtained from 90 human liver donor specimens and were transplanted into 3942 mice. Multivariate analysis revealed improved viability with younger donors (P = 0.038) as well as with shorter warm ischemic time (P = 0.012). Hepatocyte engraftment, assessed by the posttransplant level of serum human alpha1-antitrypsin, was improved with shorter warm ischemia time. Hepatocytes isolated from older donors (>or=60 years) had lower viability and posttransplant engraftment (P

Assessment of Human Islet Labeling with Clinical Grade Iron Nanoparticles Prior to Transplantation for Graft Monitoring by MRI

Cell Transplantation. 2010  |  Pubmed ID: 20719068

Ex vivo labeling of islets with superparamagnetic iron oxide (SPIO) nanoparticles allows posttransplant MRI imaging of the graft. In the present study, we compare two clinical grade SPIOs (ferucarbotran and ferumoxide) in terms of toxicity, islet cellular uptake, and MRI imaging. Human islets (80-90% purity) were incubated for 24 h with various concentrations of SPIOs (14-280 μg/ml of iron). Static incubations were performed, comparing insulin response to basal (2.8 mM) or high glucose stimulation (16.7 mM), with or without cAMP stimulation. Insulin and Perl's (assessment of iron content) staining were performed. Electronic microscopy analysis was performed. Labeled islets were used for in vitro or in vivo imaging in MRI 1.5T. Liver section after organ removal was performed in the same plane as MRI imaging to get a correlation between histology and radiology. Postlabeling islet viability (80 ± 10%) and function (in vitro static incubation and in vivo engraftment of human islets in nude mice) were similar in both groups. Iron uptake assessed by electron microscopy showed iron inclusions within the islets with ferucarbotran, but not with ferumoxide. MRI imaging (1.5T) of phantoms and of human islets transplanted in rats, demonstrated a strong signal with ferucarbotran, but only a weak signal with ferumoxide. Signal persisted for >8 weeks in the absence of rejection. An excellent correlation was observed between radiologic images and histology. The hepatic clearance of intraportally injected ferucarbotran was faster than that of ferumoxide, generating less background. A rapid signal decrease was observed in rejecting xenogeneic islets. According to the present data, ferucarbotran is the most appropriate of available clinical grade SPIOs for human islet imaging.

Are Stem Cells a Cure for Diabetes?

Clinical Science (London, England : 1979). Jan, 2010  |  Pubmed ID: 19807695

With the already heightened demand placed on organ donation, stem cell therapy has become a tantalizing idea to provide glucose-responsive insulin-producing cells to Type 1 diabetic patients as an alternative to islet transplantation. Multiple groups have developed varied approaches to create a population of cells with the appropriate characteristics. Both adult and embryonic stem cells have received an enormous amount of attention as possible sources of insulin-producing cells. Although adult stem cells lack the pluripotent nature of their embryonic counterparts, they appear to avoid the ethical debate that has centred around the latter. This may limit the eventual application of embryonic stem cells, which have already shown promise in early mouse models. One must also consider the potential of stem cells to form teratomas, a complication which would prove devastating in an immunologically compromised transplant recipient. The present review looks at the progress to date in both the adult and embryonic stem cells fields as potential treatments for diabetes. We also consider some of the limitations of stem cell therapy and the potential complications that may develop with their use.

Liraglutide, a Long-acting Human Glucagon-like Peptide 1 Analogue, Improves Human Islet Survival in Culture

Transplant International : Official Journal of the European Society for Organ Transplantation. Mar, 2010  |  Pubmed ID: 19821955

The culture of human islets is associated with approximately 10-20% islet loss, occasionally preventing transplantation. Preconditioning of the islets to improve postculture yields would be of immediate benefit, with the potential to increase both the number of transplanted patients and their metabolic reserve. In this study, the effect of liraglutide, a long-acting human glucagon-like peptide 1 analogue, on cultured human islets was examined. Culture with liraglutide (1 micromol/l) was associated with a preservation of islet mass (significantly more islets at 24 and 48 h, compared to control; P < or = 0.05 at 24 and 48 h) and with the presence of larger islets (P < or = 0.05 at 48 h). These observations were supported by reduced apoptosis rates after 24 h of treatment. We also demonstrated that human islet engraftment is improved in C57Bl/6-RAG(-/-) mice treated with liraglutide 200 microg/kg sc twice daily (P < or = 0.05), suggesting that liraglutide should be continued after transplantation. Overall, these data demonstrate the beneficial effect of liraglutide on cultured human islets, preserving islet mass. They support the design of clinical studies looking at the effect of liraglutide in clinical islet transplantation.

Selection of Patients with Hepatocellular Carcinoma Before Liver Transplantation: Need to Combine Alpha-fetoprotein with Morphology?

Hepatobiliary & Pancreatic Diseases International : HBPD INT. Oct, 2010  |  Pubmed ID: 20943453

Detecting Rejection After Mouse Islet Transplantation Utilizing Islet Protein-stimulated ELISPOT

Cell Transplantation. 2011  |  Pubmed ID: 21054945

Improved posttransplant monitoring and on-time detection of rejection could improve islet transplantation outcome. The present study explored the possibility of detecting harmful events after mouse islet transplantation measuring the immune responsiveness against islet extracts. Mouse islet transplantations were performed using various donor/recipient combinations, exploring autoimmune (NOD/SCID to NOD, n = 6) and alloimmune events (C57BL/6 to BALB/c, n = 20), a combination of both (C57BL/6 to NOD, n = 8), the absence of both (BALB/c to BALB/c, n = 21), or naive, nontransplanted control mice (n = 14). The immune reactivity was measured by ELISPOT, looking at the ex vivo release of IFN-γ from splenocytes stimulated by islet donor extracts (sonicated islets). The immune reactivity was not altered in the syngeneic and autoimmune models, demonstrating similar levels as nontransplanted controls (p = 0.46 and p = 0.6). Conversely, the occurrence of an allogeneic rejection alone or in combination to autoimmunity was associated to an increase in the level of immune reactivity (p = 0.023 and p = 0.003 vs. respective controls). The observed increase was transient and lost in the postrejection period or after treatment with CTLA4-Ig. Overall, allogeneic rejection was associated to a transient increase in the reactivity of splenocytes against islet proteins. Such a strategy has the potential to improve islet graft monitoring in human and should be further explored.

Immune Monitoring of Pancreatic Islet Graft: Towards a Better Understanding, Detection and Treatment of Harmful Events

Expert Opinion on Biological Therapy. Jan, 2011  |  Pubmed ID: 21073277

Long-term clinical outcomes of islet transplantation are hampered by rejection and recurrence of autoimmunity, which lead to a gradual decrease in islet function usually taking place over the first five years after transplantation. An accurate monitoring strategy could allow for the detection and treatment of harmful immune events, potentially resulting in higher rates of insulin-independence.

L&#39;impact De Sirolimus Sur L&#39;hépatite C Après Transplantation Hépatique Récidive

Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. Jan, 2011  |  Pubmed ID: 21258665

Bien que certaines stratégies d&#39;immunosuppression peut accélérer l&#39;hépatite C (VHC) récidive après transplantation hépatique (TH), l&#39;impact de sirolimus (SRL) n&#39;est pas connue.

The Impact of Waiting List Alpha-fetoprotein Changes on the Outcome of Liver Transplant for Hepatocellular Carcinoma

Journal of Hepatology. Oct, 2011  |  Pubmed ID: 21334400

Liver transplantation is a recognized treatment for selected patients with hepatocellular carcinoma (HCC), but transplant criteria still need to be refined, especially in the case of more advanced or downstaged tumors.

Influence of Donor Age on Islet Isolation and Transplantation Outcome

Transplantation. Feb, 2011  |  Pubmed ID: 21344706

It has been suggested that the age of human organ donors might influence islet isolation and transplantation outcome in a negative way due to a decrease of in vivo function in islets isolated from older donors.

Liver Mass with Central Calcification

Hepatology (Baltimore, Md.). Apr, 2011  |  Pubmed ID: 21480344

Appendectomy During the Third Trimester of Pregnancy in a 27-year Old Patient: Case Report of a "near Miss" Complication

Patient Safety in Surgery. 2011  |  Pubmed ID: 21575272

The management of acute appendicitis during pregnancy is not fully established, especially regarding the choice between open and laparoscopic surgery during the third trimester. We report herein the case of a major uterine variecele hemorrhage during a laparoscopic appendectomy in a 27-year old pregnant patient at 33 weeks of amenorrhea. After conversion to a Pfannenstiel incision, the baby was delivered, the bleeding stopped and the appendectomy completed. While both mother and child fully recovered, this «near miss» complication underlines the challenges linked to the management of acute appendicitis during pregnancy. Based on a literature review, we propose an algorithm favoring the laparoscopic approach during the first and second trimesters, and the open approach during the third trimester (especially after the 26th week of amenorrhea). In case of unclear pre-operative diagnosis, a laparoscopy should be conducted even during the third trimester with a Mc Burney conversion when the diagnosis of appendicitis is confirmed.

Which Matters Most: Number of Tumors, Size of the Largest Tumor, or Total Tumor Volume?

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Oct, 2011  |  Pubmed ID: 21584928

The Caspase Inhibitor IDN-6556 (PF3491390) Improves Marginal Mass Engraftment After Islet Transplantation in Mice

Surgery. Jul, 2011  |  Pubmed ID: 21596412

Islet transplantation has become a viable option for selected type 1 diabetic patients; however, a significant portion need to return to exogenous insulin. The predominant factors include impaired islet engraftment and early islet loss. Caspase inhibition is a potent way to improve islet engraftment, but all tested compounds so far have not been clinically relevant. IDN-6556 (PF3491390) has already been used clinically and can be delivered orally with high portal vein concentrations.

Demographics and Outcomes of Severe Herpes Simplex Virus Hepatitis: a Registry-based Study

Journal of Hepatology. Dec, 2011  |  Pubmed ID: 21703210

Herpes simplex virus hepatitis is a rare, but severe disease, thus far only documented by case reports and short series. The present study was based on the SRTR registry, and included all listed patients for liver transplantation from 1985 to 2009 with a diagnosis of HSV hepatitis.

Complications of Elective Liver Resections in a Center with Low Mortality: a Simple Score to Predict Morbidity

Archives of Surgery (Chicago, Ill. : 1960). Nov, 2011  |  Pubmed ID: 21768406

To develop a score predicting the morbidity of liver resections in a center with low mortality.

Noninvasive Imaging Techniques in Islet Transplantation

Current Diabetes Reports. Oct, 2011  |  Pubmed ID: 21800023

Since the Edmonton trials, insulin independence can reproducibly be achieved after islet transplantation. However, a majority of patients resume insulin treatment in the first 5 years after transplantation. Several mechanisms have been proposed but are difficult to pinpoint in one particular patient. Current tools for the metabolic monitoring of islet grafts indicate islet dysfunction when it is too late to take action. Noninvasive imaging of transplanted islets could be used to study β-cell mass and β-cell function just after infusion, during vascularization or autoimmune and alloimmune attacks. This review will focus on the most recent advances in various imaging techniques (bioluminescence imaging, fluorescence optical imaging, MRI, and positron emission tomography). Emphasis will be placed on pertinent approaches for translation to human practice.

Impact of the Number of Infusions on 2-year Results of Islet-after-kidney Transplantation in the GRAGIL Network

Transplantation. Nov, 2011  |  Pubmed ID: 21926944

Insulin independence after islet transplantation is generally achieved after multiple infusions. However, single infusion would increase the number of recipients. Our aim was to evaluate the results of islet-after-kidney transplantation according to the number of infusions.

AEB071 (sotrastaurin) Does Not Exhibit Toxic Effects on Human Islets in Vitro, nor After Transplantation into Immunodeficient Mice

Islets. Nov-Dec, 2011  |  Pubmed ID: 21934354

AEB071 (AEB, sotrastaurin), a specific inhibitor of protein kinase C, reduces T-lymphocyte activation and cytokine release. AEB delays islet allograft rejection in rats and prevents rejection when combined with cyclosporine. Since many immunosuppressive agents have toxic effects on the function of transplanted islets, we investigated whether this was also the case with AEB. Human islets were transplanted into Rag-knockout mice randomly assigned to vehicle control, AEB or sirolimus treatment groups. Non-fasting blood glucose levels, body weight and glucose tolerance was measured in recipients. In a separate experiment, human islets were cultured in the presence of AEB and assayed for glucose dependent insulin secretion and level of β-cell apoptosis. Eighty-six percent of the AEB-treated recipients achieved normoglycemia following transplant (compared with none in sirolimus-treated group, p < 0.05). AEB-treated recipients exhibited similar glucose homeostasis as vehicle-treated controls, which was better than in sirolimus-treated recipients. Human islets cultured with AEB showed similar rates of β-cell apoptosis (p = 0.98 by one-way ANOVA) and glucose stimulated insulin secretion (p = 0.15) as those cultured with vehicle. These results suggest that AEB is not associated with toxic effects on islet engraftment or function. AEB appears to be an appropriate immunosuppressive candidate for clinical trials in islet transplantation.

Splenic Rupture After Colonoscopy

The American Journal of Emergency Medicine. Feb, 2011  |  Pubmed ID: 20825894

Further Evidence for Amyloid Deposition in Clinical Pancreatic Islet Grafts

Transplantation. Jan, 2012  |  Pubmed ID: 22193043

The reasons for the long-term complete or partial loss of islet graft function are unknown, but there are obviously other reasons than just pure allogeneic graft rejection. Earlier studies have shown that deposition of islet amyloid polypeptide amyloid in transplanted islets may indicate a mechanism for loss of β cells.

A Score Predicting Survival After Liver Retransplantation for Hepatitis C Virus Cirrhosis

Transplantation. Apr, 2012  |  Pubmed ID: 22267157

Approximately one fourth of patients transplanted for hepatitis C virus (HCV)-induced liver failure progress to cirrhosis within 5 years, potentially requiring retransplantation. Although the relisting decision can be difficult in these patients, a score could help in selection of candidates with the best potential outcomes.

A Model for Dropout Assessment of Candidates with or Without Hepatocellular Carcinoma on a Common Liver Transplant Waiting List

Hepatology (Baltimore, Md.). Jan, 2012  |  Pubmed ID: 22271250

In many countries, the allocation of liver grafts is based on the Model of End-stage Liver Disease (MELD) score and the use of exception points for patients with hepatocellular carcinoma (HCC). With this strategy, HCC patients have easier access to transplantation than non-HCC ones. In addition, this system does not allow for a dynamic assessment, which would be required to picture the current use of local tumor treatment. This study was based on the Scientific Registry of Transplant Recipients and included 5,498 adult candidates of a liver transplantation for HCC and 43,528 for non-HCC diagnoses. A proportional hazard competitive risk model was used. The risk of dropout of HCC patients was independently predicted by MELD score, HCC size, HCC number, and alpha-fetoprotein. When combined in a model with age and diagnosis, these factors allowed for the extrapolation of the risk of dropout. Because this model and MELD did not share compatible scales, a correlation between both models was computed according to the predicted risk of dropout, and drop-out equivalent MELD (deMELD) points were calculated. CONCLUSION: The proposed model, with the allocation of deMELD, has the potential to allow for a dynamic and combined comparison of opportunities to receive a graft for HCC and non-HCC patients on a common waiting list.

Herpes Simplex Virus Load to Monitor Antiviral Treatment After Liver Transplantation for Acute Herpetic Hepatitis

Antiviral Therapy. 2012  |  Pubmed ID: 22290285

Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF), primarily affecting immunocompromised patients. So far, 148 cases have been published, of which 9 underwent liver transplantation (LT). The reported post-transplant survival is poor, with over 60% dying in the first year. Dosing and duration of antiviral therapy after LT are not established. Concerns include both the risk of hepatic recurrence after LT and emergence of viral resistance during prolonged therapy. HSV DNA plasma levels might be helpful to monitor therapeutic response and guide duration of therapy. We present a case of ALF complicating a primary HSV-1 infection in an immunocompetent host, who required emergency LT. We further discuss the value of measuring serial HSV DNA plasma loads to monitor antiviral therapy.

Adult Hepatoblastoma: Learning from Children

Journal of Hepatology. Jun, 2012  |  Pubmed ID: 22326463

Hepatoblastoma is the most common malignant liver tumour in infants and young children. Its occurrence in the adult population is debated and has been questioned. The aim of this paper is to review the histological and clinical features of adult hepatoblastoma as described in the adult literature, and to compare the findings with those of paediatric hepatoblastoma. The developmental and molecular aspects of hepatoblastoma are reviewed and their potential contribution to diagnosis of adult hepatoblastoma discussed. Case reports of adult hepatoblastoma identified by a PubMed search of the English, French, German, Italian, and Spanish literature through March 2011 were reviewed. Forty-five cases of hepatoblastoma were collected. Age at presentation was variable. Survival was uniformly poor, except for the rare patients who presented with the relatively differentiated, foetal type. The common denominator between adult and paediatric cases is the occurrence of embryonal or immature aspect of the tumours. Whether the adult cases of hepatoblastoma represent blastemal tumours, stem cell tumours, or unusual differentiation patterns in otherwise more frequent adult liver tumours remains to be established. Adult tumours labelled as hepatoblastoma are characterised by malignant appearing mesenchymal components. Surgical management is the cornerstone of therapy in children and also appears to confer an improved prognosis in adults. Whether adult hepatoblastoma exists, remains controversial. Indeed, several features described in adult cases are markedly different from hepatoblastoma as it is understood in children, and other differential diagnoses should also be entertained. Nonetheless, hepatoblastoma should be considered in adults presenting with primary liver tumours in the absence of pre-existing liver disease. Adult and paediatric patients with immature hepatoblastoma appear to have worse outcomes, and adults presenting with presumed hepatoblastoma have an overall poorer prognosis than children with hepatoblastoma. In all patients, surgery should be the treatment of choice, neoadjuvant chemotherapy is advisable.

Management of a Ruptured Hydatid Cyst Involving the Ribs: Dealing with a Challenging Case and Review of the Literature

International Journal of Surgery Case Reports. 2012  |  Pubmed ID: 22503916

Hydatid liver cysts can rupture into neighboring structures in 15-60% of patients, and most often involves the bile duct, the bronchi, and the peritoneal/pleural cavities. Rarely, chest or abdominal wall involvement occurs that are challenging to manage. This case report and literature review describes the management of patients with chest wall and rib invasion.

Factors Predicting Survival After Post-transplant Hepatocellular Carcinoma Recurrence

Journal of Hepato-biliary-pancreatic Sciences. Jun, 2012  |  Pubmed ID: 22710887

Although factors associated with an increased risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been extensively studied, the history of patients with a post-transplant recurrence is poorly known.

Posttransplant Cellular Immune Reactivity Against Donor Antigen Correlates with Clinical Islet Transplantation Outcome: Towards a Better Posttransplant Monitoring

Cell Transplantation. 2012  |  Pubmed ID: 22963841

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-γ (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine quantification (Bioplex). Islet function correlated with the number of IFN-γ-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 ≤ 0.0001), while no difference was observed in CD8(+)Ki67(+) and CD56(+)Ki67(+) cells. IFN-γ, IL-5, and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFN-γ-ELISpot, proliferation, and cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 ± 0.088, 0.85 ± 0.084, and 0.88 ± 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.

A Survival Analysis of the Liver-first Reversed Management of Advanced Simultaneous Colorectal Liver Metastases: a LiverMetSurvey-based Study

Annals of Surgery. Nov, 2012  |  Pubmed ID: 23095621

Liver-first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver-directed chemotherapy, the resection of the CRLM, and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80% of patients can successfully undergo a complete RM, whereas less than 30% of those undergoing classical management (CM) do so. This registry-based study compared the 2 approaches.

Takotsubo Syndrome Secondary to Adrenal Adenocarcinoma: Cortisol As a Possible Culprit

American Journal of Respiratory and Critical Care Medicine. Nov, 2012  |  Pubmed ID: 23155219

Donor Hypernatremia Influences Outcomes Following Pediatric Liver Transplantation

European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery ... [et Al] = Zeitschrift Für Kinderchirurgie. Feb, 2013  |  Pubmed ID: 23165516

With the rising demand for liver transplantations (LTs), and the shortage of organs, extended criteria including donor hypernatremia have been adopted to increase the donor pool. Currently, there is conflicting evidence on the effect of donor hypernatremia on outcomes following LT. Our aim was to investigate differences in outcome in patients receiving grafts from hypernatremic donors compared with patients receiving grafts from normonatremic donors in the pediatric population.

The Impact of Wait List Body Mass Index Changes on the Outcome After Liver Transplantation

Transplant International : Official Journal of the European Society for Organ Transplantation. Feb, 2013  |  Pubmed ID: 23199077

Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post-transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13-1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84-0.96, and HR = 0.86, 95% CI: 0.79-0.93 respectively). Female patients gaining weight over 18.5 kg/m(2) while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28-0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m(2) . Obesity does not constitute an absolute contraindication to liver transplantation.

Image of the Month. Abscess Due to a "lost" Stone During the Previous Cholecystectomy

JAMA Surgery. Jan, 2013  |  Pubmed ID: 23324846

International Workshop: Islet Transplantation Without Borders Enabling Islet Transplantation in Greece with International Collaboration and Innovative Technology

Clinical Transplantation. Mar, 2013  |  Pubmed ID: 23330863

Recently, initiatives have been undertaken to establish an islet transplantation program in Athens, Greece. A major hurdle is the high cost associated with the establishment and maintenance of a clinical-grade islet manufacturing center. A collaboration was established with the University Hospitals of Geneva, Switzerland, to enable remote islet cell manufacturing with an established and validated fully operational team. However, remote islet manufacturing requires shipment of the pancreas from the procurement to the islet manufacturing site (in this case from anywhere in Greece to Geneva) and then shipment of the islets from the manufacturing site to the transplant site (from Geneva to Athens). To address challenges related to cold ischemia time of the pancreas and shipment time of islets, a collaboration was initiated with the University of Arizona, Tucson, USA. An international workshop was held in Athens, December 2011, to mark the start of this collaborative project. Experts in the field presented in three main sessions: (i) islet transplantation: state-of-the-art and the "network approach"; (ii) technical aspects of clinical islet transplantation and outcomes; and (iii) islet manufacturing - from the donated pancreas to the islet product. This manuscript presents a summary of the workshop.

Systematic Review and Meta-analysis of Fibrin Sealants for Patients Undergoing Pancreatic Resection

HPB : the Official Journal of the International Hepato Pancreato Biliary Association. Mar, 2013  |  Pubmed ID: 23461684

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.

NK Cell Isolation from Liver Biopsies: Phenotypic and Functional Analysis of Low Cell Numbers by Flow Cytometry

Frontiers in Immunology. 2013  |  Pubmed ID: 23482713

Natural killer (NK) cells are considered to play a critical role in liver disease. However, the available numbers of intrahepatic lymphocytes (IHL) derived from liver biopsies (LB) for ex vivo analysis of intrahepatic NK cells is very limited; and the isolation method may hamper not only yields and viability, but also phenotype and function of IHL. The aim of the present study was therefore to (1) refine and evaluate the cell yields and viability of a modified isolation protocol from standard size needle LB; and (2) to test the effects of mechanical dissociation and enzymatic tissue digestion, as well as the analysis of very low cell numbers, on the phenotype and function of intrahepatic NK cells. Peripheral blood mononuclear cells (PBMC) and IHL, freshly isolated from the peripheral blood, LB (n = 11) or partial liver resections (n = 5), were used for phenotypic analysis by flow cytometry. NK cell function, i.e., degranulation and cytokine production, was determined by staining of CD107a and intracellular IFN-γ following in vitro stimulation. The mean weight of the LB specimens was 9.1 mg, and a mean number of 7,364 IHL/mg were obtained with a viability of >90%. Exposure of IHL and PBMC to 0.5 mg/ml collagenase IV and 0.02 mg/ml DNase I for 30 min did affect neither the viability, NK cell function, nor the percentages of CD56(+), NKp46(+), and CD16(+) NK cells, whereas the level of CD56 surface expression was reduced. The phenotype of LB-derived NK cells was reliably characterized by acquiring as few as 2,500 IHL per tube for flow cytometry. The functional assay of intrahepatic NK cells was miniaturized by culturing as few as 25,000 IHL in 25 μl (10(6)/ml) using 96-well V-bottom plates with IL-2 and IL-12 overnight, followed by a 4 h stimulation with K562 cells at a NK:K562 ratio of 1:1. In summary, we report reliable phenotypic and functional analyses of small numbers of intrahepatic NK cells isolated from LB specimens providing us with a tool to better address the emerging role of human NK cell immunobiology in liver diseases.

Integrating Sorafenib into an Algorithm for the Management of Post-transplant Hepatocellular Carcinoma Recurrence

Journal of Hepatology. Apr, 2013  |  Pubmed ID: 23567081

Three-dimensional Laparoscopy: a Step Toward Advanced Surgical Navigation

Surgical Endoscopy. Feb, 2013  |  Pubmed ID: 22806536