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1.
World J Clin Cases ; 7(20): 3194-3201, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31667169

RESUMO

BACKGROUND: Mesenchymal tumors such as perivascular epithelioid cell neoplasm (PEComa) and inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDC sarcoma) are relatively uncommon in the liver and are particularly rare in the caudate lobe. The clinical manifestations and available imaging tests lack specificity for hepatic mesenchymal tumors. To the best of our knowledge, no caudate PEComa or IPT-like FDC sarcoma has been completely resected by laparoscopy. The standard laparoscopic technique, surgical approaches, and tumor margins for potentially malignant or malignant caudate mesenchymal tumors are still being explored. AIM: To assess both the safety and feasibility of laparoscopic resection for rare caudate mesenchymal neoplasms. METHODS: Eleven patients who underwent isolated caudate lobe resection from 2003 to 2017 were identified from a prospective database. Three consecutive patients with rare caudate mesenchymal tumors underwent laparoscopic resection. Patient demographic data, intraoperative parameters, and postoperative outcomes were assessed and compared with the open surgery group. RESULTS: All procedures for the three resection patients with caudate mesenchymal tumors were completed using a total laparoscopic technique by two different approaches. The average operative time was 226 min, and the estimated blood loss was 133 mL. The average length of postoperative hospital stay was 6.3 ± 0.3 d for the laparoscopy group and 15.5 ± 2.3 d for the open surgery group (P < 0.05). There were no perioperative complications or patient deaths in this series. CONCLUSION: Laparoscopic isolated caudate lobe resection for rare mesenchymal neoplasms is a feasible and curative surgical option in selected patients.

2.
J Cancer ; 10(10): 2299-2311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258733

RESUMO

Background: Lymphocytes were reported to play a significant part in host anticancer immune responses and influence tumour prognosis. Few studies have focused on the prognostic values of aspartate aminotransferase (AST) to lymphocyte ratio (ALRI), aspartate aminotransferase to platelet count ratio index (APRI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) treated with palliative treatments. Methods: Five hundred and ninety-eight HCC patients treated with palliative therapies were retrospectively analysed. We randomly assigned patients into the training cohort (429 patients) and the validation cohort I (169 patients). Receiver operating characteristic (ROC) curves were used to identify the best cut-off values for the ALRI, APRI and SII in the training cohort and the values were further validated in the validation cohort I. Correlations between ALRI and other clinicopathological factors were also analysed. A prognostic nomogram including ALRI was established. We validated the prognostic value of the ALRI, SII and APRI with two independent cohorts, the validation cohort II of 82 HCC patients treated with TACE and the validation cohort III of 150 HCC patients treated with curative resection. In the training cohort and all the validation cohorts, univariate analyses by the method of Kaplan-Meier and multivariate analysis by Cox proportional hazards regression model were carried out to identify the independent prognostic factors. Results: The threshold values of ALRI, APRI and SII were 86.3, 1.37 and 376.4 respectively identified by ROC curve analysis in the training cohort. Correlation analysis showed that ALRI>86.3 was greatly associated with higher rates of Child-Pugh B&C, portal vein tumor thrombosis (PVTT) and ascites (P < 0.05). Correspondingly, ALRI level of HCC patients with Child-Pugh B&C, PVTT and ascites was evidently higher than that of HCC patients with Child-Pugh A, without PVTT and without ascites (P < 0.001). In the training cohort and the validation cohort I, II, III, the OS of patients with ALRI >86.3 was obviously shorter than patients with ALRI ≤86.3 (P <0.001). We identified ALRI as an independent prognostic factor by univariate and multivariate analyses both in training Cohort (HR=1.481, P=0.004), validation cohort I (HR=1.511, P=0.032), validation cohort II (HR=3.166, P=0.005) and validation cohort III (HR=3.921, P=0.010). The SII was identified as an independent prognostic factor in training cohort (HR=1.356, P=0.020) and the validation cohort II (HR=2.678, P=0.002). The prognostic nomogram including ALRI was the best in predicting 3-month, 6-month, 1-year, 2-year survival And OS among TNM, ALRI, ALRI-TNM and nomogram. Conclusions: The ALRI was a novel independent prognostic index for the HCC patients treated with palliative treatments.

3.
Aging (Albany NY) ; 10(8): 1902-1920, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089704

RESUMO

Hepatic ischemia-reperfusion (I/R) injury fundamentally influences the performance of aged liver grafts. The significance of mitophagy in the age dependence of sensitivity to I/R injury remains poorly understood. Here, we show that aging aggravated hepatic I/R injury with decreased mitophagy in mice. The enhancement of mitophagy resulted in significant protection against hepatic I/R injury. Parkin, an E3 ubiquitin ligase, was found depleted by I/R in aged livers. In oxygen-glucose deprivation reperfusion (OGD-Rep.)-treated L02 cells, parkin silencing impaired mitophagy and aggravated cell damage through a relative large mitochondrial membrane potential transition. The phosphorylation of the endoplasmic reticulum stress response protein EIF2α, which was also reduced in the aged liver, induced parkin expression both in vivo and vitro. Forty-six hepatic biopsy specimens from liver graft were collected 2 hours after complete revascularization, followed by immunohistochemical analyses. Parkin expression was negatively correlated to donor age and the peak level of aspartate aminotransferase within first week after liver transplantation. Our translational study demonstrates that aging aggravated hepatic I/R injury by impairing the age-dependent mitophagy function via an insufficient parkin expression and identifies a new strategy to evaluate the capacity of an aged liver graft in the process of I/R through the parkin expression.


Assuntos
Envelhecimento/fisiologia , Fator de Iniciação 2 em Eucariotos/metabolismo , Fígado/lesões , Traumatismo por Reperfusão/patologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular , Cinamatos/farmacologia , Fator de Iniciação 2 em Eucariotos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Glucose/administração & dosagem , Glucose/farmacologia , Transplante de Fígado , Camundongos , Oxigênio/farmacologia , Tioureia/análogos & derivados , Tioureia/farmacologia , Ubiquitina-Proteína Ligases/genética
4.
Oncol Lett ; 15(1): 855-862, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29403561

RESUMO

The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment.

5.
Biomed Pharmacother ; 97: 195-202, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29091866

RESUMO

BACKGROUND: Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1's capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. METHODS: The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. RESULTS: The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P=0.035), high levels of serum AFP (P=0.049), more frequency of node metastasis (P=0.015), later TNM stage (P=0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P=0.021), while LC3B were suggested to be negatively related with patients' PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P=0.002) and shorter 5-year progression free survival (PFS)(P=0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. CONCLUSION: ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/biossíntese , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Hepáticas/metabolismo , Proteínas Associadas aos Microtúbulos/biossíntese , Adulto , Carcinoma Hepatocelular/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida/tendências
6.
Immunology ; 154(1): 144-155, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29211299

RESUMO

A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1+  CD15+ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX-1+  CD15+ PMN-MDSC in circulation were positively associated with those in HCC tissues. LOX-1+  CD15+ PMN-MDSCs significantly reduced proliferation and IFN-γ production of T cells with a dosage dependent manner with LOX-1-  CD15+ PMNs reached negative results. The suppression on T cell proliferation and IFN-γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX-1 + CD15+ PMN were higher in LOX-1+  CD15+ PMN-MDSCs than LOX-1-  CD15+ PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX-1+ CD15+ PMN-MDSCs displayed significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1 expression and suppressive function for CD15+ PMN from health donor. For HCC patients, LOX-1+  CD15+ PMN-MDSCs were positively related to overall survival. Above all, LOX-1+  CD15+ PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular/metabolismo , Estresse do Retículo Endoplasmático , Fucosiltransferases/metabolismo , Antígenos CD15/metabolismo , Neoplasias Hepáticas/metabolismo , Células Supressoras Mieloides/metabolismo , Receptores Depuradores Classe E/metabolismo , Arginase/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Humanos , Interferons/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Ativação Linfocitária , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo
7.
Oncol Lett ; 14(5): 6277-6284, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29113278

RESUMO

Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P<0.001); however, the levels did not significantly differ between the HCC and liver cirrhosis groups (P=0.632). sGP73 had an inferior sensitivity and specificity for HCC diagnosis (27.79 and 77.96%, respectively) compared with α-fetoprotein (57.36 and 90.96%, respectively; P<0.001). In the HCC group, a high level of sGP73 was associated with aggressive clinicopathological features and independently predicted poor overall survival (OS) time (P<0.001). Additionally, in patients with resectable HCC, a high level of sGP73 was associated with significantly decreased disease-free survival (P<0.001) and OS (P=0.039) times compared with a low level of sGP73. This study demonstrated that sGP73 is unsuitable as a diagnostic marker for the early detection of HCC; however, it is an independent negative prognostic marker, providing a novel risk stratification factor and a potential therapeutic molecular target for HCC.

8.
Hepatobiliary Pancreat Dis Int ; 16(5): 480-486, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28992879

RESUMO

BACKGROUND: With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. METHODS: From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. RESULTS: The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence-free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). CONCLUSIONS: This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high-risk patients.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Nomogramas , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
9.
Oncol Lett ; 14(2): 2089-2096, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789436

RESUMO

The inflammatory microenvironment serves an important function in the progression of hepatocellular carcinoma (HCC). Peripheral blood lymphocyte-to-monocyte ratio (LMR), as a novel inflammatory biomarker combining an estimate of host immune homeostasis with the tumor microenvironment, has been identified to be a predictor of clinical outcomes in a number of malignancies. The present study aimed at investigating the prognostic value of LMR in patients with hepatitis B virus (HBV)-associated advanced HCC. A total of 174 patients with HBV-associated advanced HCC, without fever or signs of infections, were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival time. Univariate and multivariate analysis was performed using Cox's proportional hazards model. A threshold value was determined using a time-dependent receiver operating characteristic curve. Univariate and multivariate analysis identified LMR as an independent prognostic factor in overall survival (OS) time in patients with HBV-associated advanced HCC (P<0.05). The threshold value of LMR was 2.22. All patients were divided into either a low LMR group (≤2.22) or a high LMR group (>2.22). The OS time of the high LMR group was significantly longer compared with the low LMR group (P<0.001). Patients in the high LMR group exhibited a significantly increased 3-month and 6-month OS rate, compared with that of the patients within the low LMR group (P<0.001). An increased level of LMR was significantly associated with the presence of metastasis, ascites and increased tumor size (P<0.01). LMR is an independent prognostic factor of HBV-associated advanced HCC patients and an increased baseline LMR level indicates an improved prognosis.

10.
Oncol Lett ; 14(1): 705-714, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693224

RESUMO

The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622, respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575, respectively. For 3-month mortality, the prognostic value of CLIP ranked highest, followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked highest, followed by JIS. No significant difference between the AUCs of CLIP and CIS (P>0.05) in their predictive value for 3-month mortality was observed. The AUC of CLIP was significantly higher compared with that of the other staging systems (P<0.05) for predicting 6-month mortality. The χ2 values from the LRTs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 75.6, 48.4, 46.7, 36.0, 21.0, 46.8 and 7.24, respectively. The AIC values of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 1601.5, 1632.3, 1629.9, 1641.1, 1654.8, 1627.4 and 1671.1, respectively. CLIP exhibited the highest χ2 value and lowest AIC value, indicating that CLIP has the highest predictive value of cumulative survival rate. In the selected patients of the present study, CLIP was the staging system best able to predict 3- and 6-month and overall survival rates. CIS ranked second in predicting 3-month mortality.

11.
Oncotarget ; 7(38): 61378-61389, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27542216

RESUMO

BACKGROUND AND AIMS: This retrospective cohort study developed a prognostic nomogram to predict the survival of hepatocellular carcinoma (HCC) patients diagnosed as beyond Barcelona clinic liver cancer stage A1 after resection and evaluated the possibility of using the nomogram as a treatment algorithm reference. RESULTS: The predictors included in the nomogram were total tumour volume, Child-Turcotte-Pugh class, plasma fibrinogen and portal vein tumour thrombus. Patients diagnosed as beyond A1 were stratified into low-, medium- and high-risk groups using nomogram scores of 0 and 51 with the total points of 225. Patients within A1 exhibited similar recurrence-free survival (RFS) and overall survival (OS) rates compared with the low-risk group. Patients in the medium-risk group exhibited a similar OS but a worse RFS rates compared with patients within A1. The high-risk group was associated with worse RFS and OS rates compared with the patients within A1 (3-year RFS rates, 27.0% vs. 60.3%, P < 0.001; 3-year OS rates, 49.2% vs. 83.1%, P < 0.001). METHODS: A total of 352 HCC patients undergoing curative resection from September 2003 to December 2012 were included to develop a nomogram to predict overall survival after resection. Univariate and multivariate survival analysis were used to identify prognostic factors. A visually orientated nomogram was constructed using a Cox proportional hazards model. CONCLUSIONS: This user-friendly nomogram offers an individualized preoperative recurrence risk estimation and stratification for HCC patients beyond A1 undergoing resection. Resection should be considered the first-line treatment for low-risk patients.


Assuntos
Carcinoma Hepatocelular/mortalidade , Hepatectomia , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Nomogramas , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida
13.
Tumour Biol ; 37(4): 5265-73, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26561464

RESUMO

Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Doença Hepática Terminal/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Doença Hepática Terminal/sangue , Doença Hepática Terminal/epidemiologia , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Índice de Gravidade de Doença , Sódio/sangue , Análise de Sobrevida
14.
Tumour Biol ; 37(3): 2951-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26411670

RESUMO

The prognosis of hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE) is far from being identified. The present study aimed to assess the role of blood cell counts, routine liver function tests, and alanine aminotransferase to hemoglobin ratio (AHR) in predicting the progression-free survival (PFS) of these patients. A total of 243 HCC patients receiving TACE were analyzed retrospectively. Cancer of the Liver Italian Program (CLIP) score system was indentified to be the best score system for this patient subgroup according to the Akaike information criterion (AIC) index and linear trend χ (2). Then, prognostic value of parameters was determined by integration into the CLIP score system. As a result, AHR was confirmed to be an independent predictor for the PFS of HCC patients receiving TACE (p = 0.001) with the other parameters failing to reach statistical significance. Moreover, AHR improved the performance of CLIP by adjusting into it, thus improving its discriminatory ability. AHR defined ≤0.4583 as low level and >0.4583 as high level. And, patients were also dichotomized into two groups accordingly. HCC patients receiving TACE with low AHR presented higher 1 year DCR (41.9 vs 18.1 %) compared with patients with high AHR levels. Furthermore, AHR level was associated with prognostic factors such as lower ALP, total bilirubin, and portal vein thrombosis. In summary, the present study firstly indentified AHR as an independent prognostic factor in HCC patients receiving TACE. The subgroup of HCC patients with lower AHR presented preferable disease control and were the idealistic candidates for TACE.


Assuntos
Alanina Transaminase/sangue , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hemoglobinas/análise , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Criança , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade
15.
World J Gastroenterol ; 21(38): 10898-906, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26478681

RESUMO

AIM: To investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR) in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. METHODS: Clinicopathological data of 210 hepatitis B virus (HBV)-associated HCC patients who were treated by radical hepatic resection between 2003 and 2010 were retrospectively analyzed. None of the patients received any preoperative anticancer therapy or intraoperative radiofrequency ablation. The diagnosis was confirmed by pathological examination after surgery. Absolute peripheral blood lymphocyte and monocyte counts were derived from serum complete blood cell count before surgery, and LMR was calculated by dividing lymphocyte count by monocyte count. The best cutoff was determined by receiver operating characteristics (ROC) curve analysis. Correlations between LMR levels and clinicopathological features were assessed using the χ(2) test. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of LMR and other clinicopathological factors on overall survival (OS) and recurrence-free survival (RFS), using the Cox proportional hazards model. RESULTS: The optimal cutoff value of LMR for survival analysis was 3.23, which resulted in the most appropriate sensitivity of 55.3% and specificity of 74.7%, with the area under the curve (AUC) of 0.66 (95%CI: 0.593-0.725). All patients were dichotomized into either a low (≤ 3.23) LMR group (n = 66) or a high (> 3.23) LMR group (n = 144). A low preoperative LMR level was significantly correlated with the presence of cirrhosis, elevated levels of total bilirubin and larger tumor size. Patients with a low LMR level had significantly reduced 5-year OS (61.9% vs 83.2%, P < 0.001) and RFS (27.8% vs 47.6%, P = 0.009) compared to those with a high LMR level. Multivariate analyses indicated that a lower LMR level was a significantly independent predictor of inferior OS (P = 0.003) and RFS (P = 0.006). Subgroup analysis indicated that survival outcome was significantly more favorable in cirrhotic patients with LMR > 3.23. However, there were no differences between low and high LMR groups for OS and RFS in non-cirrhotic patients. CONCLUSION: Preoperative LMR was demonstrated for the first time to serve as an independent prognostic factor in HBV-associated HCC patients after curative resection. Prospective studies with larger cohorts for validation are warranted.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Linfócitos , Monócitos , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida
16.
Hepatobiliary Pancreat Dis Int ; 14(5): 477-84, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26459723

RESUMO

BACKGROUND: No staging systems of hepatocellular carcinoma (HCC) are tailored for assessing recurrence risk. We sought to establish a recurrence risk scoring system to predict recurrence of HCC patients receiving surgical curative treatment (liver resection or transplantation). METHODS: We retrospectively studied 286 HCC patients with preserved liver function receiving liver resection (n=184) or transplantation (n=102). Independent risk factors were identified to construct the recurrence risk scoring model. The recurrence free survival and discriminatory ability of the model were analyzed. RESULTS: Total tumor volume, HBsAg status, plasma fibrinogen level were included as independent prognostic factors for recurrence-free survival and used for constructing a 3-factor recurrence risk scoring model. The scoring model was as follows: 0.758 x HBsAg status (negative: 0; positive: 1) + 0.387 x plasma fibrinogen level (≤ 3.24 g/L: 0; >3.24 g/L: 1) + 0.633 x total tumor volume (≤ 107.5 cm3: 0; > 107.5 cm3: 1). The cut-off value was set to 1.02, and we defined the patients with the score ≤ 1.02 as a low risk group and those with the score > 1.02 as a high risk group. The 3-year recurrence-free survival rate was significantly higher in the low risk group compared with that in the high risk group (67.9% vs 41.3%, P < 0.001). In the subgroup analysis, liver transplantation patients had a better 3-year recurrence-free survival rate than the liver resection patients in the low risk group (80.0% vs 64.0%, P < 0.01). Additionally for patients underwent liver transplantation, we compared the recurrence risk model with the Milan criteria in the prediction of recurrence, and the 3-year recurrence survival rates were similar (80.0% vs 79.3%, P = 0.906). CONCLUSION: Our recurrence risk scoring model is effective in categorizing recurrence risks and in predicting recurrence-free survival of HCC before potential surgical curative treatment.


Assuntos
Carcinoma Hepatocelular/patologia , Fibrinogênio/metabolismo , Antígenos de Superfície da Hepatite B/sangue , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/sangue , Carga Tumoral , Adulto , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Curva ROC , Estudos Retrospectivos , Fatores de Risco
17.
Asian Pac J Cancer Prev ; 16(15): 6311-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26434835

RESUMO

BACKGROUND: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. MATERIALS AND METHODS: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. RESULTS: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision- making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. CONCLUSIONS: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.


Assuntos
Tomada de Decisões , Relações Familiares , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/patologia , Neoplasias/terapia , Educação de Pacientes como Assunto/métodos , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Participação do Paciente , Prognóstico
18.
World J Gastroenterol ; 21(18): 5598-606, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25987785

RESUMO

AIM: To evaluate the impact of postoperative infectious complications on hepatocellular carcinoma following curative hepatectomy. METHODS: We performed a retrospective analysis of 200 hepatocellular carcinoma patients who underwent hepatectomy at our institution between September 2003 and June 2011. The patients' demographics, clinicopathological characteristics and postoperative infectious complications were analyzed. The Clavien-Dindo classification was adopted to assess the severity of complications. The dynamic change in the neutrophil-to-lymphocyte ratio, defined as the absolute neutrophil count divided by the absolute lymphocyte count, after surgery was also investigated. The observation endpoints for this study were recurrence-free survival and overall survival of the patients. Statistical analysis of the survival curves was performed using the Kaplan-Meier method and the log-rank test. The prognostic value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. The cutoff score for each variable was selected based on receiver operating characteristic curve analysis. All statistical tests were two-sided, and significance was set at P < 0.05. RESULTS: The median age of the patients was 49 years, and the majority of patients were male (86%) and had been infected with hepatitis B virus (86%). The 30-d postoperative infectious complication rate was 34.0% (n = 68). Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (P < 0.001). The postoperative intra-abdominal infection group exhibited a worse prognosis than the non-intra-abdominal infection group (P < 0.001). A significantly increased incidence of postoperative intra-abdominal infection was observed in the patients with hepatic cirrhosis (P = 0.028), concomitant splenectomy (P = 0.007) or vascular invasion (P = 0.026). The patients who had an elevated postoperative neutrophil-to-lymphocyte ratio change (> 1.643) clearly exhibited poorer recurrence-free survival than those who did not (P = 0.009), although no significant correlation was observed between overall survival and the change in the postoperative neutrophil-to-lymphocyte ratio. Based on multivariate analysis, hepatitis B surface antigen positivity, Child-Turcotte-Pugh class B, an elevated postoperative neutrophil-to-lymphocyte ratio change and intra-abdominal infection were significant predictors of poor recurrence-free survival. Hepatic cirrhosis, the maximal tumor diameter and intra-abdominal infection were significant predictors of overall survival. CONCLUSION: Postoperative intra-abdominal infection adversely affected oncologic outcomes, and the change in postoperative neutrophil-to-lymphocyte ratio was a good indicator of tumor recurrence in hepatocellular carcinoma patients after curative hepatectomy.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Infecção da Ferida Cirúrgica/microbiologia , Adulto , Idoso , Área Sob a Curva , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Infecção da Ferida Cirúrgica/sangue , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Oncol Lett ; 10(5): 2691-2698, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26722228

RESUMO

Mature microRNA (miRNA) 34a-5p, which is a well-known tumor suppressor in hepatitis virus-associated hepatocellular carcinoma (HCC), plays an important role in cell processes, such as cell proliferation and apoptosis, and is therefore an optimal biomarker for future clinical use. However, the role of miRNA-34a-5p in chemoresistance has yet to be identified. In the present study, the expression of miRNA-34a-5p was assessed by an in situ hybridization assay in HCC tissues and was found to be significantly decreased compared with the pericarcinomatous areas of the tissue specimens, which consisted of samples obtained from 114 patients with HCC. High expression of miRNA-34a-5p was found to be associated with a favorable overall survival time in HCC patients. Functional tests performed by transfecting miRNA-34a-5p mimics or inhibitors into MHCC-97L cells illustrated that miRNA-34a-5p inhibited proliferation, elevated apoptosis and decreased chemoresistance to cisplatin in HCC cells. AXL is the direct target of miRNA-34a-5p, as confirmed by sequence analysis and luciferase assay. Transfection of the cells with small interfering RNA for AXL (siAXL) increased the apoptosis ratio of the MHCC-97L cell line. Transfection with siAXL led to similar biological behaviors in the MHCC-97L cells to those induced by ectopic expression of miRNA-34a-5p. Thus, it was concluded that miRNA-34a-5p enhanced the sensitivity of the cells to chemotherapy by targeting AXL in hepatocellular carcinoma. In addition, low expression of miRNA-34a-5p in HCC tissues yielded an unfavorable prognosis for patients with HCC that received radical surgery, due to the promotion of proliferation and an increase in chemoresistance in HCC cells.

20.
Asian Pac J Cancer Prev ; 16(18): 8665-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26745134

RESUMO

BACKGROUND AND AIMS: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. METHODS: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. RESULTS: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. CONCLUSION: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Guanina/análogos & derivados , Artéria Hepática , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/terapia , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Guanina/administração & dosagem , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Ativação Viral/efeitos dos fármacos , Adulto Jovem
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