Protocolo de transplante hepático para metástase colorretal irressecável / Protocol for liver transplantation in unresectable colorectal metastasis

RESUMO - RACIONAL: O câncer colorretal é a terceira neoplasia mais frequente e metade dos pacientes desenvolvem metástase hepática. O melhor fator prognóstico na metástase hepática de câncer colorretal (MHCCR) é a possibilidade de ressecção com margens livres, porém a maioria permanece irressecável. O racional em realizar transplante hepático (TH) em pacientes portadores de MHCCR está na ampliação do número de pacientes ressecáveis através de uma hepatectomia total. OBJETIVO: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com MHCCR irressecável. MÉTODO: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela Universidade de Oslo. A elaboração foi dividida em 4 etapas. RESULTADO: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. CONCLUSÃO: Foi possível elaborar protocolo de transplante hepático para MHCCR irressecável a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

ABSTRACT - BACKGROUND: Colorectal cancer (CRC) is the third most common neoplasm, and half of the patients with CRC develop liver metastasis. The best prognostic factor for colorectal liver metastasis (CRLM) is the possibility of performing a resection with free margins; however, most of them remain unresectable. The justification for performing liver transplantation (LT) in patients with CRLM regards an increase in the number of resectable patients by performing total hepatectomy. AIM: The aim of this study was to provide a Brazilian protocol for LT in patients with unresectable CRLM. METHOD: The protocol was carried out by two Brazilian institutions, which perform a large volume of resections and LTs, based on the study carried out at the University of Oslo. The elaboration of the protocol was conducted in four stages. RESULT: A protocol proposal for this disease is presented, which needs to be validated for clinical use. CONCLUSION: The development of an LT protocol for unresectable CRLM aims to standardize the treatment and to enable a better evaluation of surgical results.

Protocol for liver transplantation in hilar cholangiocarcinoma / Protocolo de transplante hepático para colangiocarcinoma hilar

ABSTRACT Background: Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy. Aim: To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma. Method: The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages. Result: A protocol proposal for this disease is presented, which needs to be validated for clinical use. Conclusion: The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.

RESUMO Racional: O colangiocarcinoma hilar representa mais da metade de todos os casos de colangiocarcinoma; tem prognóstico reservado e sobrevida global mediana de 12- 24 meses após o diagnóstico. A proposta de realizar transplante hepático surgiu para ampliar a possibilidade de margens livres através de hepatectomia total nos portadores de tumoresirressecáveis com melhor prognóstico. Objetivo: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com colangiocarcinoma hilar. Método: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela MayoClinic. A elaboração foi dividida em quatro etapas. Resultado: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. Conclusão: Foi possível elaborar protocolo de transplante hepático para colangiocarcinoma a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

Tiempo para el trasplante como predictor de la recurrencia del Carcinoma Hepatocelular después del trasplante hepático: Un estudio de cohorte retrospectivo / Time to transplantation as predictor of hepatocellular recurrence after liver transplantation: a retrospective cohort study

Hepatocellular recurrence after liver transplantation (LTx) is a major cause of morbidity and mortality. We aimed to investigate the association between waiting time and hepatocellular carcinoma (HCC) recurrence in patients undergoing LTx for HCC. We studied 250 patients who underwent LTx between 2007-2015. Survival and recurrence curves were calculated according to the Kaplan­Meier method and compared by the log-rank test. Univariate hazard ratios for predictors of post-LTx HCC recurrence were determined by Cox proportional hazards regressions. There were no signifcant differences in recurrence rates when stratifed by wait time to transplant. There were also no signifcant differences in rates of recurrence when the short (< 165 days) and long (> 335 days) wait-time groups were combined, although in this pooled group the 1-year and 5-year cumulative likelihoods of HCC recurrence were higher than in the group with a wait time of 165-334 days. Other predictors of recurrence were microvascular invasion, explant beyond Milan Brazil criteria and tumor diameter ≥ 2.6. This study found no association between wait time to transplantation and recurrence rates in patients who received LTx for HCC and confrmed that variables associated with tumor biology are associated with HCC recurrence.

La recurrencia hepatocelular después del trasplante de hígado (TxH) es una de las principales causas de morbi-mortalidad. Nuestro objetivo fue investigar la asociación entre el tiempo de espera y la recurrencia del carcinoma hepatocelular (CHC) en pacientes sometidos a TxH para CHC. Estudiamos 250 pacientes que se sometieron a TxH entre 2007-2015. Las curvas de supervivencia y recurrencia se calcularon de acuerdo con el método Kaplan-Meier y se compararon mediante logrank test. Las proporciones de riesgo univariados para los predictores de recurrencia posterior al TxH fueron determinadas por las regresiones proporcionales de riesgos de Cox. No hubo diferencias signifcativas en las tasas de recurrencia cuando se estratifcaron por el tiempo de espera para el trasplante. Tampoco hubo diferencias signifcativas en las tasas de recurrencia cuando se combinaron los grupos de tiempo de espera cortos (< 165 días) y largos (> 335 días), aunque en este ultimo grupo las probabilidades acumuladas de recurrencia de HCC de 1 año y 5 años fueron mayores que en el grupo con un tiempo de espera de 165-334 días. Otros predictores de recurrencia fueron la invasión microvascular, nu cumplir con criterios de Milán Brasil y el diámetro del tumor ≥2,6. Este estudio no encontró ninguna asociación entre el tiempo de espera para trasplante y las tasas de recurrencia en pacientes que recibieron LTx para HCC y confrmó que las variables asociadas con la biología tumoral están asociadas con la recurrencia del HCC.