Molekulare Nachweis Von Zirkulierenden Beta-Zellen Nach Der Insel-Transplantation

Diabetes. Mar, 2002  |  Pubmed ID: 11872650

Menschlichen Inseln Retransplantation Bei Einem Patienten Mit Typ I Diabetes

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

Kippschalter Fas-vermittelte Glucose-Signalisierung in Menschlichen Pankreatischen Beta-Zellen Vor Apoptose Zu Zellreplikation

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

Prostaglandin E (1) Schützt Menschlichen Leber Sinusförmigen Endothelzellen Vor Apoptose, Die Durch Hypoxie Induziert Reoxygenierung

Microvascular Research. Jul, 2002  |  Pubmed ID: 12074635

Mögliche Auswirkungen Der in Situ Leber Aufspaltung Von Der Anzahl Der Verfügbaren Transplantate

Transplantation. Jul, 2002  |  Pubmed ID: 12151735

Senkung Des Blutzuckers Variabilität Im Typ 1 Diabetiker Von Inselzellen Der Bauchspeicheldrüse Transplantation Behandelt: Interesse Der Kontinuierlichen Glukose-Monitoring

Diabetes Care. Dec, 2002  |  Pubmed ID: 12453970

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.

Nieren-Pankreas-Transplantation in Eine Langfristige Non-Progressor HIV-infizierten Empfänger

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

Intra-Portal Injektion Von 400 - Microm Mikrokapseln in Einer Großen Tiermodell

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

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.

Insulin Unabhängigkeit Nach Der Umstellung Auf Tacrolimus Und Sirolimus-basierte Immunsuppression Bei Insel-Nieren-Empfänger

Transplantation. Oct, 2003  |  Pubmed ID: 14557767

Aktivierung Humaner Makrophagen Durch Allogene Inseln Vorbereitungen: Hemmung Durch AOP-RANTES Und Heparinoide

Immunology. Apr, 2004  |  Pubmed ID: 15056378

Sind Kriterien Für Die Inselzellen Der Bauchspeicheldrüse Und Spender Hinreichend Verschieden, Um Wettbewerb Zu Minimieren?

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

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.

Makrophagen Depletion Verlängert Diskordanten Aber Nicht Konkordant Inselchen Xenograft Überleben

Transplantation. Mar, 2005  |  Pubmed ID: 15753843

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.

Mikrobielle Überwachung Während Der Menschlichen Inselzellen Der Bauchspeicheldrüse Isolation

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

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.

Wirkung Von Mikrokapselzusammensetzung Und Kurzfristige Immunsuppression Auf Intraportaler Biokompatibilität

Cell Transplantation. 2005  |  Pubmed ID: 15881425

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.

Behandlung Von Fulminantes Leberversagen Durch Transplantation Von Mikroverkapselten Primär- Oder Aufgrund Fortgesetzter Xenogeneic Hepatozyten

Xenotransplantation. Nov, 2005  |  Pubmed ID: 16202069

Ziel dieser Studie war, in vitro und in-vivo-Funktionen der isolierten Hepatozyten nach Immortalization, Kryokonservierung, Kapselung und Xenotransplantation in Mäuse mit fulminanten Leberversagen (FLF) zu bewerten.

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-basierte Immunsuppression Nach Lebertransplantation Für Hepatozellulären Karzinom: Langfristige Ergebnisse Und Nebenwirkungen

Transplantation. May, 2007  |  Pubmed ID: 17496530

Langfristige Ergebnisse und Nebenwirkungen berichten wir nach der Transplantation für hepatozellulären Karzinom (HCC) mit de Novo, Sirolimus-basierte Immunsuppression (IS).

ABO-inkompatible Lebertransplantation Für Schwerkranke Erwachsenen Patienten

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

ABO inkompatibel (ABO-In) Lebertransplantation bleibt eine umstrittene Lösung für akute Leberversagen bei Erwachsenen. Erwachsene Leber Empfänger mit akutem Leberversagen oder stark Dekompensierte Endstadium Krankheit, überführt und/oder in der Intensivstation, wurden als ABO-In gruppiert (n = 14), ABO-kompatiblen (n = 29, ABO-C) und ABO-identisch (n = 65, ABO-Id). ABO-In empfangenen Vierbettzimmer Immunsuppression mit Antikörper abbauenden Induktions-Agenten (außer zwei), Calcineurin-Inhibitoren, Antimetaboliten und Steroide. Wurde kein signifikanter Unterschied von Patient und Transplantat-Überleben unter ABO, ABO-C und ABO-Id beobachtet: Pfropfen überleben waren 64 %, 62 % und 67 %, jeweils in 1 Jahr und 56 %, 54 % und 60 %, bzw. in 5 Jahren; Patienten überleben 86 %, 69 % und 67 %, bzw., in 1 Jahr und 77 %, 61 % und 62 %, bzw. in 5 Jahren. Drei ABO-In Transplantate wurden (eine hyper-akute Ablehnung und zwei hepatische Arterie Thrombose) verloren. Chirurgische und infektiöse Komplikationen wurden ebenso zwischen Gruppen, außer die hepatische Arterie Thrombose, häufiger im ABO-In verteilt (2, 14 %) als ABO-ich (1, 1,5 %, P < 0,05). Im Gegensatz zu früheren Studien konnte kein signifikanter Unterschied von Patient und Transplantat-Überleben unter allen ABO-Kompatibilitätseinstellungen beobachtet werden. Unsere Ergebnisse legen nahe, dass ABO-inkompatible Transplantation eine wichtige therapeutische Option bei erwachsenen Patienten mit akutem Leberversagen, die Erwartung eines Dringlichkeitsverfahrens verstanden werden darf.

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.

Gesamt Tumorvolumen Prognostiziert Risiko Eines Rückfalls Nach Lebertransplantation Bei Patienten Mit Hepatozellulären Karzinom

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

Kriterien für die Auswahl der Kandidaten für eine Lebertransplantation in Anwesenheit von hepatozellulären Karzinom (HCC) sollte genau vorhersagen, posttransplant Wiederholung während der Kandidatur nicht übermäßige Anzahl von Patienten auszuschließen. Vorhandene Kriterien stehen vor der Herausforderung durch die begrenzte Genauigkeit der radiologische Bewertung. Die gesamte Tumorvolumen (TTV) wurde durch die Hinzufügung des Volumens jedes einzelnen Tumor berechnet. Eine vorläufige Analyse erfolgte am HCC Patientendaten aus dem Alberta Leber Transplant-Programm (52 Patienten) und dann auf die Populationen der Universitäten von Toronto und Colorado Programme (154 und 82 Patienten) validiert. Eine TTV Eckfrequenz von 115 cm(3) wurde auf der Grundlage das Risiko eines Rückfalls mit Einsatz eines Empfängers Betrieb Kennlinie ausgewählt. Radiologie korreliert enger, Pathologie mit TTV als mit Milan und University of California in San Francisco (UCSF) Kriterien (91 % im Vergleich zu 69 % und 75 % der Patienten, P < 0,0001). Obwohl mehr Patienten Qualifikationskriterien für die Transplantation mit TTV (28 % - 53 % mehr als Milan und 16-26 % mehr als UCSF) erfüllt, zeigte sich keine Verschlechterung des Ergebnisses in einer Analyse der Patienten innerhalb von TTV < oder = 115 cm(3) im Vergleich zu denen Mailand oder UCSF Klassifizierungen an alle Einrichtungen treffen. Patienten mit TTV > 115 cm(3) erlebt mehr Wiederholungen und niedrigere Patienten Überleben in der Alberta und Colorado-Serie (P < 0,05). Wenn TTV mit einem Lieferstopp von 115 cm(3) für Auswahl der Kandidaten verwendet wird, ist die Genauigkeit der pretransplant radiologische Bewertung unterscheidet sich nicht von denen mit Mailand und UCSF Klassifikationen trotz einer integrativeren Patientengruppe erreicht posttransplant Behandlungsergebnisse verbessert.

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).

Die Neubewertung Auswahlkriterien Vor Lebertransplantation Für Hepatozellulären Karzinom Unter Verwendung Der Wissenschaftlichen Registrierung Von Transplant Empfänger-Datenbank

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

Das aktuelle Modell der Leber Transplantat Zuteilung im Ort in den Vereinigten Staaten bevorzugt Transplantation von Patienten mit kleinen hepatozellulären Karzinomen (HCCs) innerhalb der Milan-Kriterien (ein einzelner Tumor bis 5 cm im Durchmesser oder bis zu drei Läsionen, keine größer als 3 cm). Obwohl mehrere Berichte suggerieren, dass diese Kriterien ausgeweitet werden könnte, gibt es derzeit keine Einigung über neue Auswahl-Werkzeuge. In dieser Studie führten wir eine Übersicht der 6478 erwachsen Dienstleistungsempfänger eine isolierte erste Lebertransplantation in der wissenschaftlichen Registrierung von Transplant Empfänger (SRTR)-Datenbank registriert. Von März 2002 bis Januar 2008, steigende Zahl von Patienten außerhalb der Milan-Kriterien (P < oder = 0,001) für eine Transplantation, aber sie noch stellen weniger als 5 % der Transplantationen durchgeführt für HCC registriert wurden. Alle getesteten Variablen (Tumor-Anzahl, größte Tumor-Größe und Mailand und der Universität von Kalifornien in San Francisco-Kriterien) nur Gesamtvolumen Sie Tumor (TTV; P < oder = 0,05) und alpha-Fetoprotein (AFP; P < oder = 0,001) könnten Patienten überleben vorherzusagen. Während diese beiden Parameter unabhängige Verhalten gezeigt hat (kein Patient zeigte eine Zunahme der beiden Werte), wurde eine zusammengesetzte Partitur mit Patienten mit einer TTV > 115 cm(3) oder ein AFP > 400 ng/mL wird außen Kriterien definiert. Die kombinierte TTV/AFP Ergebnis effizient vorhergesagten posttransplant Überleben (Hazard-Ratio = 2, 95 % Konfidenzintervall = 1,7-2.4, P < oder = 0,001); ein Überleben weniger als 50 % in 3 Jahren hatten Patienten, die diesen Kriterien nicht entsprechen. Fazit: Nach den vorliegenden Daten SRTR, Milan-Kriterien sind zu restriktiv, und Patienten mit größeren TTV zufriedenstellende posttransplant überleben genießen können. Eine zusammengesetzte Patientenselektion Partitur Kombination TTV und AFP war die effektivste aller getesteten staging-Kriterien für die Vorhersage des posttransplant Patienten Überleben für Kandidaten mit 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.

Die Geschätzte Anzahl Von Patienten Mit Hepatozellulären Karzinom, Die Für Eine Lebertransplantation Von Erweiterte Selektionskriterien Ausgewählt

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

In letzter Zeit mehrere Gruppen haben erweiterte Kriterien für die Auswahl von Patienten mit Hepatozelluläres Karzinom (HCC) vor der Transplantation eingeführt, aber die genaue Zahl der potentiellen neu eingestellte Patienten bleibt unklar. Diese Registrierung basierende Studie bewertet 270 Patienten mit HCC diagnostiziert. Die mögliche Anzahl der Transplantation Kandidaten wurde auf der Grundlage von Alter (< oder = 65 Jahre), Fehlen von Metastasen und Makro-vaskuläre Invasion, sowie auf 12 zuvor veröffentlicht, Auswahlkriterien erweitert. Eine Vielzahl von Zunahme der Zahl der Transplantation Kandidaten wurde beobachtet (12-63 % im Vergleich mit der Anzahl der solche Kandidaten, die ausgewählt wurden ausschließlich auf der Grundlage der Milan-Kriterien). Die konservativsten Kriterien waren Seoul (Kwon, 2007, um 12 %), Valencia (Silva, 2008; 16 %), Gesamt Tumor Volume/alpha-fetoprotein (Toso, 2009; 20 %) und UCSF (Yao, 2007; 20 %). Diese Daten helfen bei der Vorhersage der Bedarf an Ressourcen, die zu einer Erweiterung der Kriterien verknüpft Zentren und Politik-Agenturen.

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.

Die Auswirkungen Der Sirolimus Hepatozyten Verbreitung Nach Lebenden Spender Leber-Transplantation

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

Gibt es einen Mangel an Daten über die Nutzung von Sirolimus nach teilweiser Lebertransplantation, insbesondere im Hinblick auf ihre Auswirkungen auf die nach der Transplantation Aufbereitung.

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.

Sirolimus-basierte Immunsuppression Ist Erhöhte Überleben Nach Lebertransplantation Für Hepatozellulären Karzinom Zugeordnet

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

Lebertransplantation ist eine wichtige Behandlungsoption bei ausgewählten Patienten mit operierbarem Hepatozelluläres Karzinom (HCC). Mehrere Berichte haben ein geringeres Risiko des Wiederauftretens posttransplant Tumor mit dem Einsatz von Sirolimus und ein höherer mit Calcineurin-Inhibitoren vorgeschlagen, aber die Auswahl eines idealen Immunsuppression-Protokolls ist noch Gegenstand der Diskussion. Ziel dieser Studie war die Immunsuppression verbunden mit dem besten Überleben nach Lebertransplantation für HCC zu definieren. Sie wurde auf der Grundlage der wissenschaftlichen Registry Transplant Empfänger und enthielt 2.491 Erwachsenen Empfänger der isolierten Lebertransplantation für HCC und 12.167 für nicht-HCC Diagnosen von März 2002 bis März 2009. Alle Patienten blieb auf stabile Wartung Immunsuppression Protokolle für mindestens 6 Monate Posttransplant. In einer multivariaten Analyse nur Anti-CD25 Antikörper Induktions- und Erhaltungstherapie mit Sirolimus basierende wurden mit verbesserten Überleben nach der Transplantation für HCC (Hazard-Ratio [HR] 0.64, 95 % Konfidenzintervall [CI]: 0,45-0.9, P < oder = 0,01; HR 0.53, 95 % CI: 0.31-0.92, P < oder = 0,05, beziehungsweise). Die anderen untersuchten Drogen, einschließlich Calcineurin-Inhibitoren, erhebliche Auswirkungen nicht nachweisen. In einer Bemühung zu verstehen, ob die beobachteten Effekte durch einen direkten Einfluss der Droge auf Tumor oder mehr auf Leber wurden transplant im Allgemeinen, wir haben eine ähnliche Analyse auf nicht-HCC-Patienten durchgeführt. Obwohl Anti-CD25 Induktion wieder ein Trend zu verbesserten überleben zugeordnet wurde, zeigten Sirolimus Trend zu niedrigeren Raten des Überlebens in nicht-HCC-Empfänger, die Besonderheit ihrer positiven Auswirkungen Krebspatienten bestätigt. Fazit: Diese Angaben zufolge wirkt Sirolimus-basierte Immunsuppression einzigartige posttransplant auf HCC-Patienten, die zu verbesserten überleben führen.

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.

Die Auswirkungen Der Sirolimus Auf Hepatitis C Wiederholung Nach Lebertransplantation

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

Während einige Strategien Immunsuppression Hepatitis C-Virus (HCV) Wiederholung nach Lebertransplantation (LT) beschleunigen können, ist die Auswirkung der Sirolimus (SRL) nicht bekannt.

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