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1.
Liver Transpl ; 21(4): 512-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25675946

RESUMO

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.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Técnicas de Apoio para a Decisão , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Seleção de Pacientes , Listas de Espera , Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Distribuição de Qui-Quadrado , Emergências , França , Humanos , Estimativa de Kaplan-Meier , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Modelos Logísticos , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Listas de Espera/mortalidade
2.
J Hepatol ; 60(3): 579-89, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24211743

RESUMO

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.


Assuntos
Degeneração Hepatolenticular/cirurgia , Transplante de Fígado , Adolescente , Adulto , Idoso , Criança , Feminino , França , Sobrevivência de Enxerto , Degeneração Hepatolenticular/mortalidade , Humanos , Terapia de Imunossupressão , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
3.
Ann Surg ; 257(5): 807-15, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23532105

RESUMO

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.


Assuntos
Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Seleção de Pacientes , Adolescente , Adulto , Idoso , Europa (Continente) , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/mortalidade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
J Hepatol ; 57(3): 564-71, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22613001

RESUMO

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.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Antivirais/efeitos adversos , Ciclosporina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Genótipo , Hepacivirus/fisiologia , Hepatite C/complicações , Hepatite C/patologia , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Interferon-alfa/efeitos adversos , Rim/fisiologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Transplante de Fígado , Modelos Logísticos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Recidiva , Ribavirina/efeitos adversos , Tacrolimo/uso terapêutico , Resultado do Tratamento , Carga Viral
5.
J Hepatol ; 57(2): 297-305, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22521348

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Criança , Pré-Escolar , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Taxa de Sobrevida
6.
Clin Transplant ; 26(2): 199-207, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21517997

RESUMO

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.


Assuntos
Transplante de Fígado , Soluções para Preservação de Órgãos , Adenosina , Adulto , Alopurinol , Dissacarídeos , Eletrólitos , Feminino , Glutamatos , Glutationa , Sobrevivência de Enxerto , Histidina , Humanos , Insulina , Transplante de Fígado/efeitos adversos , Masculino , Manitol , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/diagnóstico , Rafinose
7.
Transpl Int ; 25(3): 283-93, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22239105

RESUMO

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.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Fígado , Tacrolimo/administração & dosagem , Adulto , Idoso , Biomarcadores/metabolismo , Creatinina/metabolismo , Estudos Cross-Over , Esquema de Medicação , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Resultado do Tratamento
8.
Liver Int ; 31(6): 792-801, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21645209

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diferenciação Celular , Técnicas de Apoio para a Decisão , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Seleção de Pacientes , Adulto , Algoritmos , Carcinoma Hepatocelular/mortalidade , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , França , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
J Gastroenterol Hepatol ; 26(12): 1772-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22097939

RESUMO

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.


Assuntos
Antígenos HLA/genética , Hepatite C/genética , Hepatite C/terapia , Histocompatibilidade/genética , Transplante de Fígado , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
10.
JSLS ; 15(1): 86-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21902950

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Robótica/métodos , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Laparoscopia/métodos , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
11.
BMC Cancer ; 10: 190, 2010 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-20459775

RESUMO

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).


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Imunossupressores/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Sirolimo/uso terapêutico , Austrália , Canadá , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Europa (Continente) , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Estudos Prospectivos , Proteínas Serina-Treonina Quinases/metabolismo , Recidiva , Fatores de Risco , Serina-Treonina Quinases TOR , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento
12.
Transpl Int ; 23(3): 313-24, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19843296

RESUMO

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.


Assuntos
Corticosteroides/administração & dosagem , Soro Antilinfocitário/administração & dosagem , Ciclosporina/administração & dosagem , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Adolescente , Adulto , Idoso , Animais , Emulsões , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Estudos Prospectivos , Coelhos , Linfócitos T/imunologia , Adulto Jovem
13.
J Gastroenterol Hepatol ; 25(3): 591-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19968745

RESUMO

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.


Assuntos
Veias Hepáticas , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Derivação Portocava Cirúrgica , Adulto , Idoso , Anastomose Cirúrgica/métodos , Estudos de Viabilidade , Feminino , Sobrevivência de Enxerto , Veias Hepáticas/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Turk J Pediatr ; 52(6): 662-4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21428204

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Transplante de Fígado , Síndrome de Reye/cirurgia , Humanos , Lactente , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/cirurgia , Masculino , Síndrome de Reye/induzido quimicamente , Síndrome de Reye/patologia , Síndrome de Reye/fisiopatologia
15.
Transplantation ; 85(3): 486-90, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18301342

RESUMO

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.


Assuntos
Ciclosporina/farmacologia , Transplante de Rim , Sirolimo/farmacologia , Doadores de Tecidos , Doença Aguda , Adolescente , Adulto , Idoso , Ciclosporina/efeitos adversos , Relação Dose-Resposta a Droga , Rejeição de Enxerto , Humanos , Imunossupressores/farmacologia , Rim/fisiopatologia , Pessoa de Meia-Idade , Projetos Piloto , Sirolimo/efeitos adversos
16.
Clin Dev Immunol ; 2008: 715769, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19277202

RESUMO

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.


Assuntos
Linfócitos B/imunologia , Reação Enxerto-Hospedeiro/imunologia , Transplante de Fígado/imunologia , Sistema ABO de Grupos Sanguíneos/imunologia , Animais , Hemólise/imunologia , Humanos , Síndrome , Transplante Homólogo/imunologia
17.
Bull Acad Natl Med ; 192(8): 1657-67; discussion 1667-8, 2008 Nov.
Artigo em Francês | MEDLINE | ID: mdl-19445379

RESUMO

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.


Assuntos
Hepatite C Crônica/prevenção & controle , Transplante de Fígado , Antivirais/uso terapêutico , Epitopos/imunologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/imunologia , Hepacivirus/fisiologia , Anticorpos Anti-Hepatite C/imunologia , Antígenos da Hepatite C/imunologia , Hepatócitos/virologia , Interações Hospedeiro-Patógeno , Humanos , Terapia de Imunossupressão/efeitos adversos , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/virologia , Recidiva , Virulência , Ligação Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Replicação Viral
18.
J Cardiovasc Surg (Torino) ; 58(2): 351-359, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27998045

RESUMO

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.


Assuntos
Transplante de Rim/métodos , Equipe de Assistência ao Paciente , Papel Profissional , Especialização , Cirurgiões , Procedimentos Cirúrgicos Vasculares , Aortografia , Comportamento Cooperativo , Embolização Terapêutica/efeitos adversos , Humanos , Comunicação Interdisciplinar , Transplante de Rim/efeitos adversos , Nefrectomia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiopatologia , Artéria Renal/cirurgia , Obstrução da Artéria Renal/etiologia , Obstrução da Artéria Renal/terapia , Retratamento , Cirurgiões/psicologia , Coleta de Tecidos e Órgãos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/métodos
20.
Bull Acad Natl Med ; 190(7): 1495-506; dsicussion 1506-9, 2006 Oct.
Artigo em Francês | MEDLINE | ID: mdl-17450682

RESUMO

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.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma Neuroendócrino/cirurgia , Cistadenocarcinoma/cirurgia , Veias Mesentéricas/cirurgia , Pâncreas/cirurgia , Neoplasias Pancreáticas/cirurgia , Veia Porta/cirurgia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Implante de Prótese Vascular , Causas de Morte , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia , Pancreaticojejunostomia , Complicações Pós-Operatórias , Fatores de Risco , Estômago/cirurgia
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