SUMMARY Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole exome sequencing and DNA copy number analyses, and 196 HCC also by DNA methylation, RNA, miRNA, and proteomic expression. DNA sequencing and mutation analysis identified significantly mutated genes including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or down-regulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Purpose:The aim of this study was to analyse the changes in transfusion requirements, in patients submitted to orthotopic liver transpantation from cadaveric donors, with the use of intraoperative red blood cell salvage (Cell Saver). Methods: Data from 41 transplants were analysed. Intraoperative blood loss was calculated from the cell salvage, suction and the swabs. The autologous and heterologous transfusions were recorded The red blood salvage was performed using the Cell Saver 5 System (Haemonetics).. For analysis the patients were divided in two groups: one that used the Cell Saver and another that didn´t. Results: The median age of the patients was 50 years and the main indication for liver transplantation was cirrhosis (35 cases -85.3%). The median blood loss was 8362 + 3994 ml (with the Cell Saver) and 10824 + 7002 ml (without the Cell Saver) and the median transfusion of heterologous packed red blood cells was 9,6 + 8 units (with the Cell Saver) compared to 22,3 + 21 units (without the Cell Saver). Conclusions: The Cells Saver has the potential to reduce the need for heterologous blood transfusion reducing the risks of transmissible diseases. Key words: Liver Transplantation. Cell Saver. Blood Transfusion. Liver Surgery. RESUMO Objetivo: O objetivo desse estudo foi analisar as mundanças na quantidade de transfusão necessária com uso doIntraoperative red blood cell salvage (Cell saver), em pacientes submetidos a transplante ortotópico de fígado, doador cadáver. Métodos: Foram avaliados dados de 41 pacientes submetidos a transplante de fígado. O sangramento foi calculado de acordo com débito do aspirador, compressas e captação do Cell saver. A reposição necessária foi avaliada de acordo com a quantidade de transfusão heteróloga e autóloga. Para análise dos dados os pacientes foram dividos em dois grupos: com e sem uso de Cell saver. Resultados: A mediana de idade foi 50 anos e principal indicação de transplante foi cirrose hepática com 35 casos (85,3%). A mediana de sangramento durante o procedimento cirúrgico 8362 + 3994 ml (com cell saver) e 10824 + 7002 ml (sem cell saver) e a mediana de transfusão de concentrado de hemácias heterólogo, durante o período de internação hospitalar 9,6 + 8 unidades (com cell saver) compar 22,3 + 21 unidades (sem cell saver). Conclusão: Uso de Cell Saver tem um potential para reduzir a quantidade de transfusão heteróloga, dimuindo o risco de transmissão de doenças.

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RESUMOO sucesso dos transplantes de fígado certamente seria comprometido se a avaliação pré-operatória dos pacientes não fosse realizada de forma adequada. Isto se justifica devido ao reconhecimento de que o sucesso da cirurgia depende, em princípio, do diagnóstico da doença de base, da determinação de sua extensão e do grau de repercussão sistêmica. No final das décadas de setenta a noventa os progressos da hepatologia na identificação das hepatites virais e no manejo da ascite e da síndrome hepatorrenal melhoraram sobremaneira a expectativa de vida do doente portador de doença hepática crônica. Mas, sem dúvida o transplante ortotópico do fígado (TOF) foi o espetacular avanço da hepatologia moderna. Atualmente o transplante é um tratamento eficaz das hepatopatias crônicas, e o índice de sobrevivência global aos 3 anos é ao redor de 80%. É, portanto, uma alternativa de tratamento indicada nos casos terminais, onde a mortalidade com tratamentos conservadores pode atingir até 70% ao final de 12 meses. Neste artigo, os autores comentam aspectos do TOF, relacionados à indicação e a sobrevida. Disponível em URL: http://www.scielo.br/acb Descritores -Transplante de fígado; Doadores; Receptores; Hepatopatias crônicas. ABSTRACTThe success of liver transplantation would be certainly compromised if the pre-operative evaluation was not adequately performed. The success of the liver transplantation depends on the diagnosis of the underlying hepatic disease, the determination of its extension and the degree of systemic repercussion. In the last 30 years, the progress in hepatology, the identification of viral hepatitis and the better management of ascitis and hepatorenal syndrome have increased the life expectancy of patients with chronic liver failure. Undoubtedly, orthotopic liver transplantation represents a great advance in modern hepatology. Nowadays, liver transplantation represents a valid therapeutic option for chronic liver diseases with (and presents) a mean survival rate of about 80% in 3 years. Thus, it is an indicated treatment in situations where the conservative treatment (would) could lead to a (incur) mortality rate as high as 70% in one year. In this article the authors comment (on) various aspects of Orthotopic Liver

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