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1.
Ann Surg ; 272(5): 855-862, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889867

RESUMO

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.


Assuntos
Carcinoma Hepatocelular/cirurgia , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle , Sirolimo/uso terapêutico , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Análise de Intenção de Tratamento , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
2.
Liver Int ; 40(8): 1961-1971, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32418358

RESUMO

BACKGROUND & AIMS: The impact of gender and donor/recipient gender mismatch on LT outcomes is controversial. The aim of this study was to compare outcomes of LT in Europe, using the ELTR database, between male and female recipients, including donor/recipient gender mismatch. METHODS: Recipient, donor and transplant characteristics were compared between male and female patients. Patient survival was compared between groups, and the impact of donor/recipient gender matching as well as donor and recipient anthropometric characteristics were evaluated as potential risk factors for post-LT death/graft loss. RESULTS: A total of 46,334 LT patients were evaluated (70.5% men and 29.5% women). Ten-year survival rate was significantly higher in female than in male recipients (66% vs 59%, P < .0001). At multivariate analysis, adjusted for indication to LT and type of graft, donor/recipient gender mismatch (HR 1.12, 95% CI 1.04-1.2; P = .003), donor age > 60 years (HR 1.09, 95% CI 1.01-1.18; P = .027) and recipient age (HR 1.02, 95% CI 1.1-1.02; P < .0001) were significantly associated with post-LT lower survival rate in men. Conversely in female recipients, donor BMI > 30 (HR 1.32, 95% CI 1.09-1.6; P = .005), donor age > 60 years (HR 1.15, 95% CI 1.01-1.32; P = .027) and recipient age (HR 1.02, 95% CI 1.01-1.02; P < .0001) were significantly associated with lower post-LT survival rate. CONCLUSIONS: Donor/recipient gender mismatch in male recipients and the use of obese donor in female recipients are associated with reduced survival after LT. Therefore, the incorporation of donor and recipient anthropometric quantities in the allocation process should be a matter of further studies, as their matching can significantly influence long-term outcomes.


Assuntos
Transplante de Fígado , Europa (Continente) , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos
3.
J Hepatol ; 71(2): 313-322, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071367

RESUMO

BACKGROUND & AIMS: Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors. METHODS: We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival. RESULTS: Among 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH - an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, p <0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, p = 0.713) or grafts (HR 0.99; p = 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61-65 years: HR 2.07, p <0.001; >65: HR 1.72, p = 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, p = 0.048) and low (<18.5 kg/m2: HR 4.29, p = 0.048) or high (>40 kg/m2: HR 1.96, p = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors. CONCLUSIONS: The number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications. LAY SUMMARY: The prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.


Assuntos
Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/cirurgia , Adulto , Fatores Etários , Índice de Massa Corporal , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Europa (Continente) , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/mortalidade , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento
4.
Transpl Int ; 31(12): 1293-1317, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30259574

RESUMO

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.


Assuntos
Hepatopatias/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/estatística & dados numéricos , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Europa (Continente)/epidemiologia , Feminino , Geografia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reoperação , Inquéritos e Questionários , Tempo para o Tratamento , Doadores de Tecidos , Adulto Jovem
5.
Pancreatology ; 15(2): 179-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25579809

RESUMO

BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.


Assuntos
Amilases/análise , Fístula Pancreática/enzimologia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
6.
J Surg Oncol ; 110(3): 313-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24737685

RESUMO

BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.


Assuntos
Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Feminino , Fluordesoxiglucose F18 , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Seleção de Pacientes , Compostos Radiofarmacêuticos , Estudos Retrospectivos
7.
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
8.
Pancreatology ; 12(1): 8-15, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22487467

RESUMO

OBJECTIVE: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. RESULTS: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. CONCLUSIONS: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients.


Assuntos
Biomarcadores Tumorais/análise , Biópsia por Agulha Fina/métodos , Endossonografia/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/análise , Feminino , Fixadores , Formaldeído , Proteínas de Homeodomínio/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Fatores de Transcrição HES-1 , Ultrassonografia de Intervenção
9.
Nephrol Dial Transplant ; 27(5): 1729-36, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22547750

RESUMO

Primary hyperoxaluria Type 1 is a rare autosomal recessive inborn error of glyoxylate metabolism, caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase. The disorder results in overproduction and excessive urinary excretion of oxalate, causing recurrent urolithiasis and nephrocalcinosis. As glomerular filtration rate declines due to progressive renal involvement, oxalate accumulates leading to systemic oxalosis. The diagnosis is based on clinical and sonographic findings, urine oxalate assessment, enzymology and/or DNA analysis. Early initiation of conservative treatment (high fluid intake, pyridoxine, inhibitors of calcium oxalate crystallization) aims at maintaining renal function. In chronic kidney disease Stages 4 and 5, the best outcomes to date were achieved with combined liver-kidney transplantation.


Assuntos
Testes Genéticos , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/terapia , Mutação/genética , Transaminases/genética , Hidratação , Humanos , Hiperoxalúria Primária/metabolismo , Rim/diagnóstico por imagem , Transplante de Rim , Oxalatos/metabolismo , Citrato de Potássio/uso terapêutico , Ultrassonografia , Vitamina B 6/uso terapêutico
10.
Surgeon ; 10(5): 267-72, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22959160

RESUMO

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for benign adrenal resection, and has been performed at our centre since 2000. We present a retrospective audit of our ten-year experience, and discuss the learning curve. METHODS: Creating a retrospective database, clinical and outcome data were collected for all resections performed over a ten-year period (2000-2010). Patients were chronologically divided into an 'early' (first 40 cases) and 'late' (subsequent cases) group to provide an insight into the learning curve. RESULTS: Over this period, 134 laparoscopic resections were performed, predominantly for benign adenomas (80.3%), with 48% of patients having primary hyperaldosteronism. There was almost equal sex distribution and mean age was 50.2 years, with a median BMI of 28.2. The mean operating time for left and right procedures were 127 and 124 min respectively, with 56.7% of resections being left sided. Our rate of conversion to open was 3.9%. Median length of stay was 4 days post-operatively. There was no mortality and 8.7% patients experienced a surgical complication. Analysis of the grouped data demonstrated a statistically significant reduction in open conversion rate (p = 0.017) and operative time (p = 0.011) in the 'late' group. Among the two groups there was no statistically significant difference in the length of stay and surgical complication rate. All results were comparable to published series in the literature. CONCLUSION: LA has proven to be a safe procedure with a low complication rate at our centre. Our data provide evidence that operative time and conversion rate improves with experience.


Assuntos
Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Feocromocitoma/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Curva de Aprendizado , Tempo de Internação , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Adulto Jovem
11.
Liver Transpl ; 16(4): 461-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20373456

RESUMO

The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for primary biliary cirrhosis (PBC; used as the reference group) or alcoholic cirrhosis (used as an example of a nonautoimmune liver disease). The 5-year survival of patients undergoing transplantation for AIH (n = 827) was 0.73 [95% confidence interval (CI) = 0.67-0.77]. This was similar to that of patients undergoing transplantation for alcoholic cirrhosis (0.74, 95% CI = 0.72-0.76, n = 6424) but significantly worse than that of patients undergoing transplantation for PBC (0.83, 95% CI = 0.80-0.85, n = 1588). Fatal infectious complications occurred at an increased rate in patients with AIH (hazard ratio = 1.8, P = 0.002 with PBC as the reference). The outcome of pediatric AIH patients was similar to that of adult patients undergoing transplantation up to the age of 50 years. However, the survival of AIH patients undergoing transplantation beyond the age of 50 years (0.61 at 5 years, 95% CI = 0.51-0.70) was significantly reduced in comparison with the survival of young adult AIH patients (0.78 at 18-34 years, 95% CI = 0.70-0.86) and in comparison with the survival of patients of the same age group with PBC or alcoholic cirrhosis. In conclusion, age significantly affects patient survival after liver transplantation for AIH. The increased risk of dying of infectious complications in the early postoperative period, especially above the age of 50 years, should be acknowledged in the management of AIH patients with advanced-stage liver disease who are listed for liver transplantation. It should be noted that not all risk factors relevant to patient and graft survival could be analyzed with the European Liver Transplant Registry database.


Assuntos
Hepatite Autoimune/diagnóstico , Hepatite Autoimune/terapia , Transplante de Fígado/métodos , Sistema de Registros , Adolescente , Adulto , Europa (Continente) , Feminino , Humanos , Isquemia , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento
12.
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
13.
Nephrol Dial Transplant ; 25(3): 960-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19892752

RESUMO

UNLABELLED: The Model for End-Stage Liver Disease (MELD) or similar scoring system is proposed in the UK for prioritization for liver transplantation. We evaluated the reproducibility of creatinine measurements and therefore MELD scores in four liver transplant units in the UK. METHODS: All transplant units were invited to participate; four agreed to do so, contributing 36 patients awaiting liver transplantation. Blood was collected from these 36 and divided into aliquots then sent to the four participating centres. Every centre measured creatinine and bilirubin for every patient. The results were analysed for the degree of agreement between centres for creatinine and MELD scores using the Bland-Altman method and Wilcoxon rank test. RESULTS: The mean creatinine value varied from 101 mumol/l in centre C to 110 micromol/l for the same sample in centre A, with significant differences between the four centres (P < 0.05, Wilcoxon signed-rank test). The MELD scores were significantly different between centre C and all other centres (P < 0.05). CONCLUSION: This study demonstrates lack of agreement in measurement of serum creatinine and MELD scoring between four UK transplant centres. A difference in two MELD points can have a significant impact on patient outcome, and these factors will have to be addressed if a UK-wide transplant list is to be initiated.


Assuntos
Creatinina/sangue , Hepatopatias/sangue , Hepatopatias/cirurgia , Transplante de Fígado , Índice de Gravidade de Doença , Adulto , Idoso , Bilirrubina/sangue , Feminino , Humanos , Irlanda , Rim/fisiopatologia , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Reprodutibilidade dos Testes , Reino Unido , Listas de Espera
14.
JOP ; 11(3): 226-9, 2010 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-20442516

RESUMO

CONTEXT: Pancreatic leak following pancreaticoduodenectomy has a major impact on postoperative mortality. However, it is not clear whether pancreatic leaks affect long term survival in patients with pancreatic ductal adenocarcinoma. OBJECTIVE: The aim of this study is to compare the long term outcome in patients who underwent pancreaticoduodenectomy, with and without postoperative pancreatic leak. PATIENTS: All 133 patients who underwent a pancreaticoduodenectomy at the HepatoPancreatoBiliary Unit, Addenbrooke's Hospital, Cambridge, between June 2002 and June 2007 were identified from a prospectively held database. The study was restricted to 47 patients who had a confirmed diagnosis of pancreatic ductal adenocarcinoma. SETTING: Pancreatic leak was defined as drain fluid amylase more than three times the serum level for more than 3 days post operatively. MAIN OUTCOME MEASURE: Long term survival of patients with and without leaks were compared using Kaplan-Meier curves and significance was measured using the log-rank test. RESULTS: Median follow-up was 30.8 months. The median actuarial survival of all ductal adenocarcinoma patients was 19 months. Pancreatic leaks occurred in 9 patients (19.1%). There were no significant differences in the overall survival or presence of recurrence between the two groups. CONCLUSIONS: Pancreatic leak following pancreaticoduodenectomy does not appear to impact on long-term outcome of patients with pancreatic ductal adenocarcinoma.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/cirurgia , Amilases/metabolismo , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/mortalidade , Carcinoma Papilar/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Bases de Dados Factuais , Neoplasias Duodenais/mortalidade , Neoplasias Duodenais/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/metabolismo
15.
Transplantation ; 104(5): 1019-1025, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31403552

RESUMO

BACKGROUND: The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS). METHODS: Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP. The primary endpoint, delayed graft function, was analyzed by "intention-to-treat" evaluation. RESULTS: There was no difference in the incidence of delayed graft function between CS and MP (32/51 (62.8%) and 30/51 (58.8%) P = 0.69, respectively), although the trial stopped early due to difficulty with recruitment. There was no difference in the incidence of acute rejection, or in graft or patient survival between the CS and MP groups. Median estimated glomerular filtration rate at 3 months following transplantation was significantly lower in the CS group compared with MP (CS 34 mL/min IQR 26-44 vs MP 45 mL/min IQR 36-60, P = 0.006), although there was no significant difference in estimated glomerular filtration rate between CS and MP at 12 months posttransplant. CONCLUSIONS: This study is underpowered, which limits definitive conclusions about the use of MP, as an alternative to static CS. It did not demonstrate that the use of MP reduces the incidence of delayed graft function in donation after circulatory death kidney transplantation.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Adolescente , Adulto , Idoso , Criopreservação/métodos , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/fisiopatologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Sobrevivência de Enxerto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido/epidemiologia , Adulto Jovem
16.
Liver Transpl ; 15(7): 747-53, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19562708

RESUMO

Aprotinin is an antifibrinolytic drug that reduces blood loss during orthotopic liver transplantation (OLT). Case reports have suggested that aprotinin may be associated with an increased risk of thromboembolic complications. Recent studies in cardiac surgery also have suggested a higher risk of renal failure and postoperative mortality. Despite these concerns, no large-scale safety assessment has been performed in OLT. In a retrospective observational study involving 1492 liver transplants, we studied the occurrence of postoperative thromboembolic or thrombotic events and mortality in patients who received aprotinin (n = 907) and patients who did not (n = 585). The overall incidence of hepatic artery thrombosis and central venous complications (pulmonary embolism or inferior vena cava thrombosis) was 3.2% and 0.9%, respectively. In propensity score-adjusted analyses (C-index = 0.79), aprotinin was not associated with an increased risk of hepatic artery thrombosis [odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.50-2.01, P = 0.86]. Although central venous complications were found more frequently in patients receiving aprotinin, the difference was not statistically significant (OR = 2.95, 95% CI = 0.54-16.23, P = 0.32). In addition, no significant differences were found in 1-year mortality (OR = 1.21, 95% CI = 0.86-1.71, P = 0.32). In conclusion, this study did not demonstrate an increased risk of thrombotic complications or mortality when aprotinin is used during OLT.


Assuntos
Aprotinina/farmacologia , Transplante de Fígado/métodos , Trombose/etiologia , Adulto , Feminino , Hemostáticos/farmacologia , Artéria Hepática/patologia , Humanos , Falência Hepática/complicações , Falência Hepática/terapia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Risco , Trombose/complicações , Resultado do Tratamento
17.
World J Surg Oncol ; 7: 55, 2009 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-19549298

RESUMO

BACKGROUND: Hepatic embryonal sarcoma (HES) is a rare but aggressive primary tumor of the liver occurring most frequently in childhood. CASE PRESENTATION: We report a case of a 52 year old woman having previously undergone treatment for ovarian serous papillary carcinoma who subsequently presented with a large solitary mass in the liver. Initially this was presumed to be metastasis from the ovarian primary however, on further examination it was shown to be a primary hepatic embryonal sarcoma. CONCLUSION: Primary liver tumors should be considered in differential diagnoses in patients with ovarian cancer who subsequently present with liver tumors. This is particularly important when there is no direct evidence of recurrence of ovarian cancer.


Assuntos
Carcinoma Papilar/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias Hepáticas/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Segunda Neoplasia Primária/patologia , Neoplasias Ovarianas/patologia , Sarcoma/patologia , Antígeno Ca-125/sangue , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/terapia , Sarcoma/terapia
18.
Surg Today ; 39(8): 669-74, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19639433

RESUMO

PURPOSE: An aberrant right hepatic artery (ARHA) is a common anomaly and its implications for patients undergoing a pancreaticoduodenectomy (PD) have not yet been previously reported. We compared the outcomes following PD in patients with and without an ARHA. A novel classification of the anatomical course of ARHA, and surgical techniques for its identification and preservation are described herein. METHODS: All patients undergoing PD between June 1, 2002, and May 31, 2007, were divided into two groups, one with ARHA and the other without. These groups were compared to identify differences in the intraoperative variables, the oncological clearance, the postoperative complications, and the survival. RESULTS: A total of 135 patients underwent PD of which 28 (20.8%) patients were found to have either accessory or replaced right hepatic arteries (ARHA group). There were no significant differences in the intraoperative variables (blood loss and operative time) and the incidence of postoperative complications (pancreatic leak and delayed gastric emptying). Oncological clearance (nodal yield and resection margins) and survival were also similar in the two groups. CONCLUSIONS: The surgical and oncological outcomes of PD remain unaffected by the presence of ARHA provided that the anatomy is recognized and appropriately managed. Aberrant right hepatic artery can be classified into three types according to their anatomical relationship with the head of the pancreas.


Assuntos
Artéria Hepática/anormalidades , Pancreaticoduodenectomia , Perda Sanguínea Cirúrgica , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Esvaziamento Gástrico , Artéria Hepática/cirurgia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Liver Transpl ; 14(10): 1473-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18825684

RESUMO

Liver transplantation provides a return to a satisfactory quality of life (QOL) for the majority of patients in the short to medium term (first 5 years), but there is very little information on the QOL in the longer term and the factors influencing it. We therefore undertook a single-center cross-sectional analysis to determine QOL in patients 10 or more years after liver transplantation. All liver transplant recipients who were followed up at the Cambridge Transplant Unit for 10 or more years (transplanted between 1968 and 1994) and resident in the United Kingdom were asked to complete by post the Short Form 36 version 2 and the Ferrans and Powers questionnaires to evaluate their QOL. Univariate and multivariate analysis were performed to assess the relationship between a range of clinical parameters and QOL. One hundred two patients were invited to participate, and 61 (59.8%) responded. Overall, the patients reported a satisfactory QOL. On the Ferrans and Powers questionnaire, the patients had a mean Quality of Life Index score of 24.5. Factors associated with reduced physical functioning were age > 50 years at transplantation, female gender, and recurrence of the primary liver disease. On the Short Form 36 version 2 questionnaire, recipients had reduced physical functioning but normal mental health parameters in comparison with the normal population. Age > 60 years at the time of survey, female gender, and posttransplant complications were associated with reduced physical functioning. In conclusion, patients 10 or more years after liver transplantation generally have a good QOL, although physical functioning is reduced. Addressing issues such as recurrent disease and posttransplant problems such as osteoporosis may help to improve long-term QOL.


Assuntos
Transplante de Fígado , Qualidade de Vida , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias , Fatores de Tempo , Reino Unido , Adulto Jovem
20.
World J Gastroenterol ; 14(44): 6867-8, 2008 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-19058316

RESUMO

Percutaneous aspiration and drainage of post-operative abdominal fluid collections is a well established standard technique. However, some fluid collections are not amenable to percutaneous drainage either due to location or the presence of surrounding visceral structures. Endoscopic Ultrasound (EUS) has been widely used for the drainage of pancreatitis-related abdominal fluid collections. However, there are no reports on the use of this technique in the post-operative setting. We report a case where the EUS-guided technique was used to drain a percutaneously inaccessible post-operative collection which had developed after Whipple's resection.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Drenagem/métodos , Endossonografia , Complicações Pós-Operatórias/cirurgia , Ultrassonografia de Intervenção , Abdome , Anastomose em-Y de Roux , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Derivação Gástrica , Humanos , Pessoa de Meia-Idade , Pancreaticojejunostomia , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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