RESUMO
OBJECTIVE: To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE). METHODS: We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE. RESULTS: Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97 months (p = 0.001) and 3.1 months vs. 5.8 months (p < 0.001). In subgroup patients, the median OS and PFS of negative and positive lipiodol deposition groups were 4.7 months vs. 10.5 months (p < 0.001) and 3.5 months vs. 7.0 months (p < 0.001), respectively. CONCLUSIONS: The patients with positive lipiodol deposition in PVTT had a longer OS than those with negative lipiodol deposition. Furthermore, the positive lipiodol deposition in PVTT can further differentiate HCC patients with favourable prognosis from SD patients. KEY POINTS: ⢠Lipiodol deposition in PVTT is a prognostic indicator for HCC patients after TACE treatment. ⢠Positive lipiodol deposition in PVTT is associated with a better prognosis.
Assuntos
Antineoplásicos/farmacocinética , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Óleo Etiodado/farmacocinética , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/metabolismo , Veia Porta/patologia , Prognóstico , Estudos Retrospectivos , Trombose/patologia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos , Procedimentos Cirúrgicos Vasculares/mortalidade , Adulto JovemRESUMO
Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, hepatitis B virus (HBV)-infected, hepatitis C virus (HCV)-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively). A polymerase chain reaction (PCR) array was used to detect the changes in transcription factor (TF) expression in hepatic stellate cells (HSCs) with SYK knockdown. The effects of SYK antagonism on liver fibrogenesis were studied in LX-2 cells, TWNT-4 cells, primary human HSCs, and three progressive fibrosis/cirrhosis animal models, including a CCL4 mouse model, and diethylnitrosamine (DEN) and bile duct ligation (BDL) rat models. We found that SYK protein in HSCs and hepatocytes correlated positively with liver fibrosis stage in human liver tissue. HBV or HCV infection significantly increased SYK and cytokine expression in hepatocytes. Increasing cytokine production further induced SYK expression and fibrosis-related gene transcription in HSCs. Up-regulated SYK in HSCs promoted HSC activation by increasing the expression of specific TFs related to activation of HSCs. SYK antagonism effectively suppressed liver fibrosis via inhibition of HSC activation, and decreased obstructive jaundice and reduced HCC development in animal models. Conclusion: SYK promotes liver fibrosis via activation of HSCs and is an attractive potential therapeutic target for liver fibrosis and prevention of HCC development. (Hepatology 2018).
Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Indazóis/uso terapêutico , Cirrose Hepática Experimental/enzimologia , Pirazinas/uso terapêutico , Quinase Syk/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Indazóis/farmacologia , Cirrose Hepática Experimental/prevenção & controle , Masculino , Camundongos Endogâmicos C57BL , Pirazinas/farmacologia , Ratos , Quinase Syk/antagonistas & inibidoresRESUMO
OBJECTIVE: The present study aimed to investigate the effectiveness of parenteral nutritional support with ω-3 PUFAs-based lipid emulsions in patients after liver resection. METHODS: A total of 119 patients were randomly assigned to the immunonutrition (IM) group (n = 59) and control group (n = 60). The IM group was continuously given Omegaven(®) 10% 100 mL/day rather than regular nutrition for five days postoperatively. Venous blood samples were obtained from all subjects before surgery and D1, D3 and D7 after surgery. RESULTS: No significant difference was found in baseline characteristics of the two groups. On D1 after surgery, no statistically significant differences were observed in the blood sample tests between the two groups. On D3 after surgery, the levels of white blood cell count (WBC), alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (TBil) were dramatically decreased in the IM group (t = 3.065, p = 0.003; t = 2.149, p = 0.034; t = 5.313, p= 0.001; and t = 2.419, p = 0.017, respectively). Furthermore, on D7 after surgery, not only could a significant decrease be observed in the IM group concerning the levels of WBC, ALT and TBil (t = 3.025, p = 0.003; t = 2.094, p = 0.038; and t = 2.046, p = 0.043, respectively), but it was also seen in the level of Δprothrombintime (PT) (t = 2.450, p = 0.016). An increase in the level of prealbumin (Pre-Alb) in the IM group was observed on D7 after surgery (t = 2.237, p = 0.027). The frequency of total complications in the IM group were significantly lower than in the control group (χ² = 4.225, p = 0.040 and χ² = 3.174, p = 0.075). The trend favored the IM group in reducing the total infective complications rate (χ² = 3.174, p = 0.075). A significant decrease in the duration of the hospital stay after surgery was also observed in the IM group (t = 2.012, p = 0.047). CONCLUSION: ω-3 PUFAs-based lipid emulsions for treatment of patients after hepatectomy are safe and effective in controlling inflammation, protecting liver function, and consequently reducing the rate of total complications and the duration of the hospital stay.