RESUMO
The underlying causes of chronic rejection (CR) after liver transplantation (LT) are not completely known. The main aim of this study was to explore the involvement of the minor histocompatibility antigen glutathione S-transferase T1 (GSTT1) in CR. We retrospectively studied 611 patients who underwent LTs at University Hospital Virgen del Rocío between 2003 and 2016 with a median follow-up of 7.4 ± 4.2 years. The GSTT1 genotype was determined by polymerase chain reaction. We defined GSTT1 mismatch as a specific donor/recipient combination in which a recipient who was homozygous for the deletion allele received a transplant from a positive donor. The prevalence of CR in our whole cohort was 11.6% (71/611), and the prevalence in the GSTT1-mismatched group was 18.8% (16/85) versus 10.5% (55/526) in the GSTT1-matched group. In the cyclosporine A (CsA) group, the prevalence was 26.3% (26/99), much higher than the 8.8% (45/512) observed in the tacrolimus (Tac) group. For statistical analysis, the patients were distributed into 2 groups: group 1, regarded as GSTT1 mismatched, which included the donor (D)+/recipient (R)- allelic combination; and group 2, regarded as GSTT1 matched, which included the other allelic combinations of D+/R+, D-/R-, and D-/R+. All relevant clinical information was collected, and a diagnosis of CR was always confirmed by liver biopsy. GSTT1 mismatch (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.08-3.66; P = 0.03) and use of CsA/Tac (P < 0.001) were independent risk factors for CR. CR increased the risk of mortality (HR, 2; 95% CI, 1.2-3.6; P = 0.01). Out of the 71 CR patients, 12 (16.9%) needed retransplantation. In conclusion, the GSTT1 D+/R- allelic mismatch is an independent risk factor for CR. A long follow-up of LT patients is recommended because the incidence of CR in adults seems to be underestimated.
Assuntos
Transplante de Fígado , Adulto , Aloenxertos , Genótipo , Glutationa Transferase/genética , Humanos , Fígado , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation. METHODS: This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders. RESULTS: Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation. CONCLUSION: Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.
Assuntos
Carcinoma Hepatocelular/cirurgia , Everolimo/administração & dosagem , Imunossupressores/administração & dosagem , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Esquema de Medicação , Everolimo/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
This review focused in the perioperative management of patients with pancreatic cancer in order to improve the outcome of the disease. We consider that the most controversial points in pancreatic cancer management are jaundice management, vascular resection and neo-adjuvant therapy. Preoperative biliary drainage is recommended only in patients with severe jaundice, as it can lead to infectious cholangitis, pancreatitis and delay in resection, which can lead to tumor progression. The development of a phase III clinical trial is mandatory to clarify the role of neo-adjuvant radiochemotherapy in pancreatic adenocarcinoma. Venous resection does not adversely affect postoperative mortality and morbidity, therefore, the need for venous resection should not be a contraindication to surgical resection in selected patients. The data on arterial resection alone, or combined with vascular resection at the time of pancreatectomy are more heterogeneous, thus, patient age and comorbidity should be evaluated before a decision on operability is made. In patients undergoing R0 resection, arterial resection can also be performed.