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1.
Liver Transpl ; 21(4): 512-23, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25675946

RESUMEN

In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/cirugía , Técnicas de Apoyo para la Decisión , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Selección de Paciente , Listas de Espera , Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/mortalidad , Distribución de Chi-Cuadrado , Urgencias Médicas , Francia , Humanos , Estimación de Kaplan-Meier , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Modelos Logísticos , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Listas de Espera/mortalidad
2.
J Hepatol ; 60(3): 579-89, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24211743

RESUMEN

BACKGROUND & AIMS: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long-term outcome of WD patients following LT. METHODS: The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18-66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7-53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). RESULTS: Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. CONCLUSIONS: Liver failure associated with WD is a rare indication for LT (<1%), which achieves an excellent long-term outcome, including renal function.


Asunto(s)
Degeneración Hepatolenticular/cirugía , Trasplante de Hígado , Adolescente , Adulto , Anciano , Niño , Femenino , Francia , Supervivencia de Injerto , Degeneración Hepatolenticular/mortalidad , Humanos , Terapia de Inmunosupresión , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
3.
Ann Surg ; 257(5): 807-15, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23532105

RESUMEN

OBJECTIVE: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.


Asunto(s)
Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Tumores Neuroendocrinos/secundario , Tumores Neuroendocrinos/cirugía , Selección de Paciente , Adolescente , Adulto , Anciano , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tumores Neuroendocrinos/mortalidad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
4.
J Hepatol ; 57(3): 564-71, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22613001

RESUMEN

BACKGROUND & AIMS: We aimed at determining the effect of maintenance therapy with ribavirin alone, after a year of combined peginterferon-alfa 2a (PegIFNα-2a) and ribavirin therapy, on viral response and liver histology after liver transplantation (LT). METHODS: Hundred and one patients with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring), 1-5years after LT, were enrolled. PegIFNα-2a and ribavirin were initiated at 90 µg/wk and 600 mg/d, respectively, then increased or adjusted as a function of tolerance. At 12 months, combination therapy was discontinued and patients were randomized to ribavirin or placebo for a further 12 months. Growth factor use was permitted. RESULTS: At 18 months, a sustained virological response (SVR) was obtained in 47.9% of patients in Per Protocol (PP) analysis, and was higher in patients with genotype 2 or 3 than in patients with genotype 1 or 4, in patients with genotypes 1+4 receiving ciclosporine than in those receiving tacrolimus, in patients with worse renal function, in those having received EPO, in patients with lower weight, and in those with lower viral load at 3 months. Using logistic regression, only the early viral response, recipient weight and renal function were independently associated with better SVR. SVR, viral load, activity, and fibrosis scores were similar, at M18 and M30, in patients randomized to ribavirin, or to placebo. CONCLUSIONS: A PP SVR was achieved in 47.9% of patients with established recurrent hepatitis C after LT. Maintenance therapy with ribavirin alone does not improve the virological response or the histological parameters.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Antivirales/efectos adversos , Ciclosporina/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Femenino , Genotipo , Hepacivirus/fisiología , Hepatitis C/complicaciones , Hepatitis C/patología , Humanos , Inmunosupresores/uso terapéutico , Quimioterapia de Inducción , Interferón-alfa/efectos adversos , Riñón/fisiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Trasplante de Hígado , Modelos Logísticos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Placebos/uso terapéutico , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Recurrencia , Ribavirina/efectos adversos , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Carga Viral
5.
J Hepatol ; 57(2): 297-305, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22521348

RESUMEN

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8 cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation < 12 months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ≥ 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Adolescente , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Niño , Preescolar , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Tasa de Supervivencia
6.
Clin Transplant ; 26(2): 199-207, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21517997

RESUMEN

The purpose of this prospective, nine-center, non-randomized study was to assess the efficacy and safety of Celsior preservation fluid in liver transplantation using unselected donors. As data comparing allograft outcomes following liver transplantation using Celsior and University of Wisconsin (UW) preservation fluids are limited, we also compared our cohort with matched controls selected from the European Liver Transplant Registry (ELTR) who received total liver grafts preserved with UW solution during the same period. One hundred and forty patients who received livers preserved with Celsior were included. The primary endpoint, graft loss at one-yr post-transplantation, was observed in 24 patients (17.1%) which was not significantly different from the 20.0% pre-defined threshold rate (95% confidence interval [CI] 10.9, 23.4; p=0.398). Predictive factors for graft loss on univariate analysis were moderate-to-severe steatosis on the donor graft (5/22 patients with graft loss vs. 8/107 patients without, p=0.046) and duration of warm ischemia (1.4±1.1 h in patients with graft loss vs. 0.9±0.5 h in patients without, p=0.034). Hepatic artery thrombosis and stenosis occurred in seven (5.0%) and six (4.3%) patients, respectively. The comparison of our patients to 420 ELTR controls showed that one-yr graft survival rates (Celsior: 82.9%, 95% CI 75.8, 88.2; UW: 78.6%, 95% CI 74.4, 82.2) and Kaplan-Meier one-yr graft survival distributions (p=0.285) were similar. Within the cold ischemia time achieved in our study, liver preservation with Celsior appeared efficient and safe. Comparison with ELTR patients suggested that liver allograft survival was similar using Celsior or UW solution for preservation of unselected donor grafts.


Asunto(s)
Trasplante de Hígado , Soluciones Preservantes de Órganos , Adenosina , Adulto , Alopurinol , Disacáridos , Electrólitos , Femenino , Glutamatos , Glutatión , Supervivencia de Injerto , Histidina , Humanos , Insulina , Trasplante de Hígado/efectos adversos , Masculino , Manitol , Persona de Mediana Edad , Disfunción Primaria del Injerto/diagnóstico , Rafinosa
7.
Transpl Int ; 25(3): 283-93, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22239105

RESUMEN

This multicenter, open-label, phase III study assessed renal function, safety, and efficacy in stable adult liver transplant recipients converted from tacrolimus twice-daily (BID) to once-daily (QD). Patients received tacrolimus BID for 6weeks before conversion to tacrolimus QD (1:1 [mg:mg] total daily dose basis) for 12weeks. Primary endpoint: change in steady state creatinine clearance (CrCl) between treatment phases. Of 112 patients enrolled, 98 were converted to QD dosing (full analysis set [FAS]). Mean (SD) tacrolimus dose was 3.7 (1.7) mg/day during BID and at conversion, and 3.9 (1.8) mg/day at Week 12. 74.5% of patients required no dose adjustment on conversion (FAS). Mean tacrolimus whole blood trough levels were at the lower end of the recommended range during tacrolimus BID and QD; the difference between mean steady-state trough levels was statistically significant (7.5ng/ml vs. 6.5ng/ml; P<0.0001). Following conversion, mean tacrolimus trough levels were reduced by 15% (about 1ng/ml) without any cases of acute rejection, remained stable during the remainder of the study, and were more consistent, showing reduced between- and within-patient variability in trough levels. Renal function remained stable, demonstrating noninferiority of tacrolimus QD versus BID (relative difference in mean calculated CrCl -0.1% [±6.3%]). Patient and graft survival were 100%. Adverse events incidence was low during both treatment phases.


Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Tacrolimus/administración & dosificación , Adulto , Anciano , Biomarcadores/metabolismo , Creatinina/metabolismo , Estudios Cruzados , Esquema de Medicación , Femenino , Supervivencia de Injerto , Humanos , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Tacrolimus/farmacocinética , Tacrolimus/uso terapéutico , Resultado del Tratamiento
8.
Liver Int ; 31(6): 792-801, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21645209

RESUMEN

AIM: To generate a new score with improved accuracy compared with Milan criteria to select patients. PATIENTS: The training cohort comprised 373 patients transplanted for hepatocellular carcinoma (HCC) between 1988 and 1998 (cohort 1). An algorithm was derived from the analysis of patient data by the proportional hazard Cox regression model. The area under the receiver operating characteristic (AUROC) was used to determine a cut-off value. The validation cohort comprised 140 patients transplanted between 1999 and 2001 (cohort 2). RESULTS: Multivariate analysis identified three predictors of 5-year tumour-free survival: tumour differentiation (P=0.02), diameter (P<0.0001) and number of nodules (P=0.04). A cut-off value of 4 was derived from the AUROC of the final score. Five-year tumour-free survival was 60.2 ± 3.1% in patients with as score <4 and 36.4 ± 4.7% in individuals with a score ≥4, P<0.0001. In the validation cohort, 5-year tumour-free survival was 82.8 ± 3.6% (score <4) and 50.0 ± 10.7% (score ≥4), P=0.0003. In patients with a score <4, there was no significant difference in 5-year tumour-free survival between Milan+ and Milan- patients, either in cohort 1 or 2. Five-year tumour-free survival of Milan- patients was significantly better in individuals with a score <4 compared with those with a score ≥4, both in cohort 1 (61.5 ± 9.1 vs 31.4 ± 4.6%, P=0.009) and in cohort 2 (P=0.02). CONCLUSION: A novel score taking into account tumour differentiation shows higher accuracy than Milan criteria in predicting 5-year tumour-free survival following liver transplantation for HCC. Prospective studies should validate these findings.


Asunto(s)
Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Diferenciación Celular , Técnicas de Apoyo para la Decisión , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Selección de Paciente , Adulto , Algoritmos , Carcinoma Hepatocelular/mortalidad , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Francia , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
9.
J Gastroenterol Hepatol ; 26(12): 1772-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22097939

RESUMEN

BACKGROUND AND AIM: The objective of this 11-year cohort retrospective study conducted in adult patients with chronic hepatitis C virus (HCV) who underwent liver transplantation (LT) was to identify whether human leukocyte antigen (HLA) mismatching is associated with the recurrence of HCV and with the time to recurrence of HCV. METHODS: Among the 181 patients (74% men; mean age: 54 years, range 25-71) who underwent a LT between 1995 and 2006 in the study center, 163 had relevant data in their medical chart documenting HCV recurrence, and 107 (65.64%) reported a histological evidence of HCV recurrence. RESULTS: Survival was 78% at 5 years. There was no significant relationship between the total score of HLA-mismatches and the recurrence of HCV. Similarly, there was no significant relationship between the total score of HLA mismatches and the time to recurrence of HCV. For the analyses at each individual locus, a significant relationship between the individual scores of HLA-mismatches and the recurrence of HCV were observed. Out of the 40 patients who experienced a rejection, the rate of recurrence was not different according to the severity of the rejection (75% mild, 64% moderate and 64% for severe rejection). CONCLUSIONS: In conclusion, this large study did not demonstrate any relationship between the total score of HLA mismatches and HCV-recurrence. Contrarily a significant relationship between the individual scores of HLA mismatches (HLA-A3, HLA-B35, HLA-DR3, HLA-DR7, HLA-DQ2, HLA-DQ2-0) and the recurrence of HCV were observed.


Asunto(s)
Antígenos HLA/genética , Hepatitis C/genética , Hepatitis C/terapia , Histocompatibilidad/genética , Trasplante de Hígado , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos
10.
JSLS ; 15(1): 86-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21902950

RESUMEN

BACKGROUND: The surgical robotic system is superior to traditional laparoscopy in regards to 3-dimensional images and better instrumentation. Robotic surgery for hepatic resection has not yet been extensively reported. The aim of this article is to report the first known case of liver resection with the use of a robot in France. METHODS: A 61-year-old male with hepatitis C liver cirrhosis and hepatocellular carcinoma was referred for surgical treatment. Preoperative clinical evaluation and laboratory data disclosed a Child-Pugh class A5 patient. Magnetic resonance imaging showed a 3.4-cm tumor in segment III. Liver size was normal, and there were not signs of portal hypertension. Five trocars were used. RESULTS: Liver transection was achieved with Harmonic scalpel and bipolar forceps without pedicle clamping. Hemostasis of raw surface areas was accomplished with interrupted stitches. Operative time was 180 minutes. Blood loss was minimal, and the patient did not receive transfusion. The recovery was uneventful, and the patient was discharged on the fifth postoperative day without ascites formation. CONCLUSION: The robotic approach may enable liver resection in patients with cirrhosis. The da Vinci robotic system allowed for technical refinements of laparoscopic liver resection due to 3-dimensional visualization of the operative field and instruments with wrist-type end-effectors.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Robótica/métodos , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Laparoscopía/métodos , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
11.
BMC Cancer ; 10: 190, 2010 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-20459775

RESUMEN

BACKGROUND: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. METHODS/DESIGN: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. DISCUSSION: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. TRIAL REGISTER: Trial registered at http://www.clinicaltrials.gov: NCT00355862(EudraCT Number: 2005-005362-36).


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Inmunosupresores/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Sirolimus/uso terapéutico , Australia , Canadá , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/mortalidad , Supervivencia sin Enfermedad , Europa (Continente) , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Estimación de Kaplan-Meier , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Estudios Prospectivos , Proteínas Serina-Treonina Quinasas/metabolismo , Recurrencia , Factores de Riesgo , Serina-Treonina Quinasas TOR , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento
12.
Transpl Int ; 23(3): 313-24, 2010 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-19843296

RESUMEN

We conducted the first prospective, randomized, open-label multicenter study in low-immunologic risk adult recipients of primary cadaver kidney transplants receiving rabbit anti-T-lymphocyte globulin, mycophenolate mofetil, cyclosporine microemulsion introduced on day 5, with and without corticosteroids. Patients were randomly assigned according to age and cold ischemia time to receive corticosteroids for at least 6 months or no corticosteroids at all. The main efficacy evaluation criterion was acute rejection (including all treated episodes and those biopsy-confirmed) during the first year following transplantation. For this purpose, this report includes the actual results of the whole 12-month follow-up of all randomized patients. For efficacy analysis, 98 patients were evaluated in the Steroid avoidance group and 99 in the Steroid maintenance group. Taken as a whole, 81% of the patients (n = 159) never received anti-rejection treatment. From the 38 patients who received anti-rejection treatment, 25 (25.5%) were in the Steroid avoidance group and 13 (13.1%) in the Steroid maintenance group (P < 0.031), experiencing respectively 17 (17.3%) and 7 (7.1%) biopsy-proven first episodes of acute rejection (P < 0.031). Borderline changes (6 vs. 3) were not considered as biopsy-proven acute rejections. Onset of first rejection was significantly shorter in the Steroid avoidance group (P < 0.027). First-line anti-rejection treatment response, need for any rescue therapy, as well as histologic severity of rejection episodes did not statistically differ between the groups. One-year post-transplantation analysis showed no differences in delayed graft function, serum creatinine, creatinine clearance, 24-h proteinuria, as well as serious adverse events between the groups. De novo diabetes (P < 0.07) or dyslipidemia (P < 0.01) as well as newly diagnosed malignancies (P < 0.059) were however more frequently observed in the Steroid maintenance group. At the end of the first post-transplant year, 99% of patients in the Steroid avoidance group and 97% of patients in the Steroid maintenance group were respectively alive (P = 0.34), with respectively 95% and 93.2% of functioning kidney grafts (P = 0.62). Our results showed that total avoidance of corticosteroids from the day of transplantation was associated with a significantly increased number of clinically diagnosed and treated, and biopsy-proven acute rejections during the first year of transplantation. Nevertheless, overall outcome, 1-year patient and graft survival as well as renal function were similar, and the patients in the Steroid avoidance group exhibited a lower incidence of de novo dyslipidemia, diabetes mellitus and malignancies often associated with steroid treatment.


Asunto(s)
Corticoesteroides/administración & dosificación , Suero Antilinfocítico/administración & dosificación , Ciclosporina/administración & dosificación , Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Adolescente , Adulto , Anciano , Animales , Emulsiones , Femenino , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/administración & dosificación , Estimación de Kaplan-Meier , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Estudios Prospectivos , Conejos , Linfocitos T/inmunología , Adulto Joven
13.
J Gastroenterol Hepatol ; 25(3): 591-6, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19968745

RESUMEN

BACKGROUND AND AIMS: The aim of this study is to analyze a single-center experience in orthotopic liver transplantation with the piggy-back technique (PB) realized with a cuff of three veins without temporary portacaval shunt. Outcome parameters were graft and patient survival and the surgical complications. METHODS: The records of 423 liver transplantation in 396 adult recipients were reviewed. PB was performed in all cases also in patients with transjugular intrahepatic portosystemic shunts and redo transplants without temporary portacaval shunt. No hemodynamic instability was observed during venous reconstruction. RESULTS: Operation time, cold ischemia time and anhepatic phase were, respectively, 316, 606 and 82 min, respectively. The mean intraoperative transfusion of packed red blood cells was 3.2 (range 1-48). Surgical complications were observed in 25% of the orthotopic liver transplantation and 2% of these was related to caval anastomosis. No case of caval thrombosis was observed; a stenosis was noted in seven patients, always treated with an endovascular approach. A postoperative ascites was observed in seven cases. Retransplantation was required in 6.3% patients. Overall in-hospital mortality was 5.3%, but no patient died through technical problems or complications related to PB procedure. One-, 3- and 5-year grafts and patients were 94%, 83% and 75%, and 92%, 86% and 79%, respectively. CONCLUSION: This experience indicates that our approach is feasible with a low specific risk and can be performed without portacaval shunt, with minimal outflow venous complications.


Asunto(s)
Venas Hepáticas , Hepatopatías/cirugía , Trasplante de Hígado/métodos , Derivación Portocava Quirúrgica , Adulto , Anciano , Anastomosis Quirúrgica/métodos , Estudios de Factibilidad , Femenino , Supervivencia de Injerto , Venas Hepáticas/cirugía , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
14.
Turk J Pediatr ; 52(6): 662-4, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21428204

RESUMEN

Reye syndrome is a rare, but severe and often fatal disease. The etiology of the classical Reye syndrome is unknown, but it is typically preceded by a viral infection with a free interval of three to five days. The main physiopathological hypothesis is a mitochondrial metabolism insult causing acute liver failure and encephalopathy. Survivors present serious neurological sequelae. The treatment of Reye syndrome is usually medical with intensive care management. Herein, we present the clinical case of a six-month-old baby diagnosed with Reye syndrome with a fulminant hepatitis, who was successfully liver transplanted with an auxiliary partial orthotopic liver transplantation.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Trasplante de Hígado , Síndrome de Reye/cirugía , Humanos , Lactante , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/cirugía , Masculino , Síndrome de Reye/inducido químicamente , Síndrome de Reye/patología , Síndrome de Reye/fisiopatología
15.
Transplantation ; 85(3): 486-90, 2008 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-18301342

RESUMEN

A 6-month, open-label, multicenter prospective pilot study was conducted to evaluate the effects of sirolimus (SRL) versus cyclosporine (CsA) in recipients of kidneys from expanded criteria donors. All patients also received antithymocyte globulins induction, mycophenolate mofetil, and steroids. Sixty-nine patients (33 SRL, 36 CsA) were randomized. More patient were withdrawn in the SRL group (16 vs. 6, P<0.01), because of delayed graft function and surgical complications. Delayed graft function tended to be more frequent with SRL than with CsA (45.4% vs. 30.6%, P=0.22). Graft survival was numerically lower in the SRL group (87.5% vs. 97%, P=0.19). At 6 months, there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance (SRL 12.1% vs. CsA 8.3%; P=0.7 and 44.7+/-16.6 vs. 41.9+/-15.2 mL/min; P=0.54 respectively). These results do not support the use of SRL immediately after transplantation in expanded criteria donor recipients.


Asunto(s)
Ciclosporina/farmacología , Trasplante de Riñón , Sirolimus/farmacología , Donantes de Tejidos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Ciclosporina/efectos adversos , Relación Dosis-Respuesta a Droga , Rechazo de Injerto , Humanos , Inmunosupresores/farmacología , Riñón/fisiopatología , Persona de Mediana Edad , Proyectos Piloto , Sirolimus/efectos adversos
16.
Clin Dev Immunol ; 2008: 715769, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19277202

RESUMEN

The authors reviewed the passenger lymphocyte syndrome (PLS) that has appeared after transplantation. The definition, mechanism, serological, clinical features, and treatment for PLS after solid organ transplantation, especially liver transplantation, are described. The PLS refers to the clinical phenomenon of alloimmune hemolysis resulting from the adoptive transfer of viable lymphocytes from donor during solid organ or hematopoietic stem cell transplant. Sometimes, it is very severe and may cause "unexplained" hemolysis during the postoperative period. The authors reviewed literature about the PLS in liver transplantation.


Asunto(s)
Linfocitos B/inmunología , Reacción Injerto-Huésped/inmunología , Trasplante de Hígado/inmunología , Sistema del Grupo Sanguíneo ABO/inmunología , Animales , Hemólisis/inmunología , Humanos , Síndrome , Trasplante Homólogo/inmunología
17.
Bull Acad Natl Med ; 192(8): 1657-67; discussion 1667-8, 2008 Nov.
Artículo en Francés | MEDLINE | ID: mdl-19445379

RESUMEN

Hepatitis C virus (HCV) is a major cause of chronic liver disease. About 170 million people worldwide are chronically infected. No preventive or therapeutic vaccine is available. Current antiviral combinations based on pegylated interferon alpha (IFN-alpha) and ribavirin have limited efficacy, poor tolerability and high cost. End-stage liver disease due to chronic HCV infection is a leading indication for liver transplantation (LT). However, re-infection of the liver graft is inevitable, with a high risk of cirrhosis within 5 years. To infect the graft, circulating virions need to attach to and enter hepatocytes, via viral envelope glycoproteins E1-E2. E1-E2 can react with cell receptors despite the presence of neutralizing antibodies. [corrected] A better understanding of the early steps of viral attachment and escape from neutralizing antibodies could lead to novel antiviral strategies.


Asunto(s)
Hepatitis C Crónica/prevención & control , Trasplante de Hígado , Antivirales/uso terapéutico , Epítopos/inmunología , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/inmunología , Hepacivirus/fisiología , Anticuerpos contra la Hepatitis C/inmunología , Antígenos de la Hepatitis C/inmunología , Hepatocitos/virología , Interacciones Huésped-Patógeno , Humanos , Terapia de Inmunosupresión/efectos adversos , Cirrosis Hepática/etiología , Cirrosis Hepática/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/virología , Recurrencia , Virulencia , Acoplamiento Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Replicación Viral
18.
J Cardiovasc Surg (Torino) ; 58(2): 351-359, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27998045

RESUMEN

Kidney transplantation is a surgical procedure involving both vascular and ureteric anastomoses. As a matter of fact, it can be performed either by urologists or vascular surgeons. However, vascular surgeon's expertise can be helpful at different times. In the present paper we describe how can vascular surgeons help at the different stages of kidney transplantation process in modern care: 1) before kidney transplantation for recipient preparation in order to allow subsequent graft implantation, either by performing percutaneous embolization of renal arteries in the setting of polycystic kidney disease or treatment of aneurysmal or occlusive lesions that would contra-indicate graft implantation; 2) at the time of surgery graft back table preparation and repair; and 3) after surgery for long-term follow-up, including transplant renal artery stenosis treatment or transplant nephrectomy.


Asunto(s)
Trasplante de Riñón/métodos , Grupo de Atención al Paciente , Rol Profesional , Especialización , Cirujanos , Procedimientos Quirúrgicos Vasculares , Aortografía , Conducta Cooperativa , Embolización Terapéutica/efectos adversos , Humanos , Comunicación Interdisciplinaria , Trasplante de Riñón/efectos adversos , Nefrectomía , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/terapia , Arteria Renal/diagnóstico por imagen , Arteria Renal/fisiopatología , Arteria Renal/cirugía , Obstrucción de la Arteria Renal/etiología , Obstrucción de la Arteria Renal/terapia , Retratamiento , Cirujanos/psicología , Recolección de Tejidos y Órganos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/métodos
20.
Bull Acad Natl Med ; 190(7): 1495-506; dsicussion 1506-9, 2006 Oct.
Artículo en Francés | MEDLINE | ID: mdl-17450682

RESUMEN

Pancreatic resection is currently the only treatment offering the possibility of long-term survival for patients with pancreatic cancer. Mesentericoportal vein involvement used to be considered a contraindication to pancreatic resection, but recent advances in vascular surgery have gradually extended the indications of curative pancreatic resection to such cases. We report hereby our experience of 100 pancreatic resections combined with mesentericoportal vein resection for pancreatic malignancies, performed between 1989 and 2005. This is one of the largest reported series. The overall mortality rate was 4% and the morbidity rate was 39%. Among the 76 patients who had pancreatic adenocarcinoma, the 5-year survival rate in case of limited mesenterico-portal vein wall involvement (up to the adventitia) was similar to that among patients without histological involvement of the portal vein wall (35.8% and 26.7%, respectively). These results support aggressive management consisting of resection and reconstruction of the mesentericoportal veins in patients with venous involvement, provided curative R0 resection is feasible.


Asunto(s)
Adenocarcinoma/cirugía , Carcinoma Neuroendocrino/cirugía , Cistadenocarcinoma/cirugía , Venas Mesentéricas/cirugía , Páncreas/cirugía , Neoplasias Pancreáticas/cirugía , Vena Porta/cirugía , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Implantación de Prótesis Vascular , Causas de Muerte , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Pancreaticoduodenectomía , Pancreatoyeyunostomía , Complicaciones Posoperatorias , Factores de Riesgo , Estómago/cirugía
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