RESUMO
BACKGROUND: Portal vein embolization is a treatment option to achieve a sufficient future remnant liver volume for patients with central liver tumours requiring an extended resection with an extensive parenchymal loss. However, molecular mechanisms of this intervention are up to now poorly understood. The objective of this prospective pilot study was the characterization of molecular events leading to late hypertrophy of the non-embolized liver tissue in the human liver. METHODS: Liver tissue of ten patients was collected before and intraoperatively more than one month after embolization. Investigation of molecular features was performed by pangenomic chips, polymerase chain reaction, immunostaining of proliferation marker Ki-67 and immunofluorescence measurements. RESULTS: Significantly elevated genes hint towards angiogenesis and signalling by insulin-like growth factor and associated binding proteins. Increased transcript levels of activator protein 1 complex members like c-jun were reflecting potential molecular events of liver growth after embolization. Immunofluorescence data confirmed a predominant upregulation of ß-catenin and c-jun (p<0.1) supported by Ki-67 (p<0.05) in the non-embolized liver. In silico analysis of transcriptomic dysplasia and hepatocellular carcinoma data showed divergent signatures compared to embolization. CONCLUSIONS: Our findings indicate a sustained regeneration after portal vein embolization reflected in hyperplasia and angiogenesis in the human liver and provide novel molecular mechanisms of interlobe crosstalk.
Assuntos
Embolização Terapêutica , Neoplasias Hepáticas/terapia , Regeneração Hepática/genética , Fígado/metabolismo , Fator 3 Ativador da Transcrição/genética , Idoso , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Hiperplasia/genética , Hiperplasia/metabolismo , Proteína 1 Inibidora de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/genética , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Neovascularização Fisiológica/genética , Projetos Piloto , Veia Porta , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-fos , Proteínas Proto-Oncogênicas c-jun/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Fator de Transcrição AP-1/genética , Transcrição Gênica , Fator de Crescimento Transformador beta/genética , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , beta Catenina/genéticaRESUMO
BACKGROUND: The nested stromal epithelial tumor (NSET) of the liver is a rare tumor entity which is being reported in young girls. CASE REPORT: In our 16-year-old female patient, we have performed a liver transplantation (LTX) for a non-metastasizing non-resectable liver tumor. The patient was tumor free in the follow-up. At 28 months postoperatively, we detected lung metastases in the F18-FDG-PET/CT. The patient died 37 months after LTX from progressive pulmonary metastases. CONCLUSION: LTX should not have been generally recommended for NSET. Further statements about the value of LTX for NSET will be possible only after evaluation of the course of the disease in a larger number of transplanted patients.