RESUMO
BACKGROUND: ALPPS procedure has been introduced to increase the volume of future liver remnant. The mechanisms underlying the accelerated regeneration observed with ALPPS are unknown. It was hypothesized that AMPK/mTOR is activated as an integrating pathway for metabolic signals leading to proliferation and cell growth. Our aim was to analyze increase in liver volume, proliferation parameters and expression of AMPK/mTOR pathway-related molecules in patients undergoing ALPPS. METHODS: A single center prospective study of patients undergoing ALPPS was performed from 2013 to 2015. Liver and serum samples, clinical laboratory results and CT-scan data were obtained. ELISA, Ki-67 immunostaining and qRT-PCR were performed in deportalized and remnant liver tissue in both stages of the procedure. RESULTS: 11 patients were enrolled. Remnant liver volume increased 112 ± 63% (p < 0.05) in 9.1 ± 1.6 days. Proliferation-related cytokines IL-6, TNF-α, HGF and EGF significantly increased, while higher Ki-67 immunostaining and cyclin D expression were observed in remnant livers after ALPPS. mTOR, S6K1, 4E-BP1, TSC1 and TSC2 expression were significantly increased in remnant livers at second stage, while AMPK and Akt increased only in deportalized liver samples. CONCLUSION: Rapid liver regeneration with ALPPS might be associated with hepatocyte proliferation induced by mTOR pathway activation.
Assuntos
Hepatectomia/métodos , Regeneração Hepática , Fígado/irrigação sanguínea , Fígado/cirurgia , Veia Porta/cirurgia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Idoso , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Citocinas/metabolismo , Ativação Enzimática , Feminino , Hepatectomia/efeitos adversos , Hepatócitos/enzimologia , Hepatócitos/patologia , Humanos , Ligadura , Fígado/diagnóstico por imagem , Fígado/enzimologia , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiopatologia , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
La evaluación psiquiátrica inicial es de suma importancia para establecer programas de operación en los distintos niveles; asistenciales, docentes y de investigación. El presente artículo describe y propone los fundamentos, características y ventajas de una unidad de evaluación psiquiátrica inicial sobre la base de un afronte interdisciplinario en el Instituto Nacional de Salud Mental Honorio Delgado-Hideyo Noguchi. Intenta, así, presentar alternativas de atención en países como el Perú, donde existen serias limitaciones en recursos humanos y materiales.
The psychiatric initial assessment is of great importance to design programs at different levels: mental health care, teaching and research. This paper describes and proposes the bases and advantages of a psychiatric interdisciplinary initial assessment unit in the National Institute of Mental health Honorio-Hideyo Noguchi. Such approach is in accordance with the scattered resources of a country like Peru.
