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1.
Medicine (Baltimore) ; 99(40): e21503, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019382

RESUMO

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), but HBV-HCC related prognosis signature remains rarely investigated. This study was to identify an integrated long non-coding RNAs-messenger RNAs (lncRNA-mRNA) signature for prediction of overall survival (OS) and explore their underlying functions.One RNA-sequencing dataset (training set, n = 95) and one microarray dataset E-TABM-36 (validation set, n = 44) were collected. Least absolute shrinkage and selection operator analysis was performed to identify an lncRNA-mRNA prognosis signature. The OS difference of patients in the high-risk and low-risk risk groups was evaluated by Kaplan-Meier curve. Area under the receiver operating characteristic curve (AUC), Harrell concordance index (C-index) calculation, and multivariate analyses with clinical characteristics were used to determine the prognostic ability. Furthermore, a coexpression network was constructed to interpret the functions.Nine signature genes (3 lncRNAs and 6 mRNAs) were selected to generate the risk score model. Patients belonging to the high-risk group showed a significantly shorter survival than those of the low-risk group. The prediction accuracy of the risk score for 5-year OS was 0.936 and 0.905 for the training set and validation set, respectively. Also, this risk score was independent of various clinical variables for the prognosis prediction. Incorporation of the risk score remarkably increased the predictive power of the routine clinical prognostic factors (vascular invasion status, tumor recurrence status) (AUC = 0.942 vs 0.628; C-index = 0.7997 vs 0.6908). Furthermore, LncRNA insulin-like growth factor 2 antisense RNA (IGF2-AS) and long intergenic non-protein coding RNA 342 (LINC00342) were predicted to exert tumor suppression effects by regulating homeobox D1 (HOXD1) and secreted frizzled related protein 5 (SFRP5), respectively; while lncRNA rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) may possess carcinogenic potential by promoting the transcription of chromobox 2 (CBX2), cell division cycle 20 (CDC20), matrix metallopeptidase 12 (MMP12), stratifin (SFN), tripartite motif containing 16 (TRIM16), and uroplakin 3A (UPK3A). These mRNAs may be associated with cell proliferation or apoptosis related pathways.This study may provide a novel, effective prognostic biomarker, and some therapeutic targets for HBV-HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco
2.
Medicine (Baltimore) ; 99(41): e22118, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031259

RESUMO

It is controversial regarding the treatment allocation for patients with stage I hepatocellular carcinoma (SI-HCC). The aim of the present study was to compare the long-term survival in SI-HCC patients undergoing liver transplantation (LT), liver resection (LR), local tumor destruction (LTD), or none. SI-HCC patients diagnosed between 2004 and 2015 were extracted from the SEER 18 registry database. Multivariable Cox models and propensity score matching (PSM) method were used to explore the association between surgical methods and long-term prognosis. A total of 5165 patients with stage I (AJCC, 6th or 7th) HCC were included in the study. Only 36.9% of patients diagnosed with HCC in stage I received surgical therapy. The incidence of LT was decreased over time (P < .001). In the multivariable-adjusted cohort (n = 5165), after adjusting potential confounding factors, a clear prognostic advantage of LT was observed in OS (P < .0001) compared with patients after LR. Patients undergoing LTD had a worse OS in comparison with patients who underwent LR (P < .0001). Patients who received no surgical treatment had the worst OS (P < .0001) among 4 treatment groups. In stratified analyses, the salutary effects of LT vs LR on OS were consistent across all subgroups except for a similar result in the noncirrhotic subgroup (P = .4414). The inferior survival effects of LTD vs LR on OS were consistent across all subgroups, and even in the subgroup with tumor size < 3 cm (P = .0342). In the PSM cohort, patients in LT group showed a better OS (P < .001) than patients in LR group (P < .0001) and patients undergoing LTD had a worse OS compared with patients who underwent LR (P = .00059). In conclusion, LT offered a survival advantage compared with LR among patients with Stage I HCC. LT is the best surgical treatment for stage I HCC in patients with advanced fibrosis, whereas LR provides comparable long-term outcomes to LT in patients without advanced fibrosis and should be considered as the first-line surgical option. LTD can be used as an alternative method when LR and LT are unavailable.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Feminino , Hepatectomia , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Programa de SEER , Análise de Sobrevida
4.
Medicine (Baltimore) ; 99(37): e21788, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925716

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common neoplasms encountered, and its incidence is increasing worldwide. In this study, we explored the characteristics of gut microbiota in patients with primary hepatocellular carcinoma in advanced stage who received immune checkpoint inhibitors (ICIs) based on a large population with hepatitis B virus infection. An initial cohort of 65 patients with metastatic melanoma were included in this study. All patients were treated with ICIs at Fujian provincial geriatric hospital between August 2016 and June 2018. The 16S rDNA V4 region was amplified by Polymerase chain reaction and sequenced on the MiSeq platform. We found that the diversities of the gut microbiota in HCC who received ICIs were obviously increased. Negative feedback, which is controlled by interplay between microbial metabolic activities and host pathways, is thought to promote high bacterial diversity. We focused on the Faecalibacterium genus in response group, and Bacteroidales order in non-response group, and stratified patients into high versus low categories based on the median relative abundance of these taxa in the gut microbiome. Patients with high Faecalibacterium abundance had a significantly prolonged PFS versus those with a low abundance. Conversely, patients with a high abundance of Bacteroidales had a shortened progressive free survival compared to those with a low abundance. In summary, the present study examined the oral and gut microbiome of HCC patients undergoing immune checkpoint inhibitors immunotherapy. Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus non-responders.


Assuntos
Carcinoma Hepatocelular/microbiologia , Microbioma Gastrointestinal , Fatores Imunológicos/uso terapêutico , Imunoterapia/mortalidade , Neoplasias Hepáticas/microbiologia , Idoso , Bacteroides/crescimento & desenvolvimento , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , China , Faecalibacterium/crescimento & desenvolvimento , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , RNA Ribossômico 16S/análise , Resultado do Tratamento
5.
Am J Clin Oncol ; 43(9): 640-647, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889834

RESUMO

BACKGROUND: The incidence of liver cancer has more than tripled since 1980. Hepatectomy represents the major curative treatment for liver cancer. The risk factors associated with 90-day mortality after hepatectomy are not well understood and there are currently no good prediction models for this outcome. The objectives of the current study were to identify risk factors of 90-day mortality after hepatectomy in patients with hepatocellular carcinoma and to develop an integer-based risk score using the National Cancer Database. METHODS: Hepatectomies recorded in the National Cancer Database during 2004-2012 were reviewed for 90-day mortality. Risk factors were identified by multivariate logistic regression models. An integer-based risk score was developed using the ß coefficients derived from the logistic regression model and tested for discriminatory ability. According to the total risk score, patients were grouped into 4 risk groups. RESULTS: The overall 90-day mortality was 10.2%. Ten risk factors were identified, which included sex, age, race/ethnicity, insurance status, education, annual hospital volume, stage, tumor grade, Charlson-Deyo Score, and surgical procedure. The risk of 90-day mortality was stratified into 4 groups. The calculated 90-day mortality rates were 2.47%, 5.88%, 12.58%, and 24.67% for low-risk, medium-risk, high-risk, and excessive-risk groups, respectively. An area under the receiver operating characteristic curve of 0.69 was obtained for model discrimination. CONCLUSIONS: The integer-based risk score we developed could easily quantify each patient's risk level and predict 90-day mortality after hepatectomy. The stratified risk score could be a useful addition to perioperative risk management and a tool to improve 90-day mortality after hepatectomy.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Área Sob a Curva , Carcinoma Hepatocelular/patologia , Estudos Transversais , Bases de Dados Factuais , Feminino , Previsões/métodos , Hepatectomia/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
6.
Medicine (Baltimore) ; 99(32): e21702, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769939

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor with unsatisfactory prognosis. The abnormal genes expression is significantly associated with initiation and poor prognosis of HCC. The aim of the present study was to identify molecular biomarkers related to the initiation and development of HCC via bioinformatics analysis, so as to provide a certain molecular mechanism for individualized treatment of hepatocellular carcinoma.Three datasets (GSE101685, GSE112790, and GSE121248) from the GEO database were used for the bioinformatics analysis. Differentially expressed genes (DEGs) of HCC and normal liver samples were obtained using GEO2R online tools. Gene ontology term and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were conducted via the Database for Annotation, Visualization, and Integrated Discovery online bioinformatics tool. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes database and hub genes were visualized by Cytoscape. Survival analysis and RNA sequencing expression were conducted by UALCAN and Gene Expression Profiling Interactive Analysis.A total of 115 shared DEGs were identified, including 30 upregulated genes and 85 downregulated genes in HCC samples. P53 signaling pathway and cell cycle were the major enriched pathways for the upregulated DEGs whereas metabolism-related pathways were the major enriched pathways for the downregulated DEGs. The PPI network was established with 105 nodes and 249 edges and 3 significant modules were identified via molecular complex detection. Additionally, 17 candidate genes from these 3 modules were significantly correlated with HCC patient survival and 15 of 17 genes exhibited high expression level in HCC samples. Moreover, 4 hub genes (CCNB1, CDK1, RRM2, BUB1B) were identified for further reanalysis of KEGG pathway, and enriched in 2 pathways, the P53 signaling pathway and cell cycle pathway.Overexpression of CCNB1, CDK1, RRM2, and BUB1B in HCC samples was correlated with poor survival in HCC patients, which could be potential therapeutic targets for HCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Biologia Computacional/estatística & dados numéricos , Programas de Rastreamento/normas , Prognóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/fisiopatologia , China/epidemiologia , Análise por Conglomerados , Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Programas de Rastreamento/métodos , Mapas de Interação de Proteínas/genética , Análise de Sobrevida
7.
Medicine (Baltimore) ; 99(34): e21887, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846849

RESUMO

INTRODUCTION: The incidence of hepatocellular carcinoma (HCC) ranks sixth in the world, but its mortality is the third highest due to the lack of early diagnostic markers. Nowadays, the increase of autoantibody levels has been found in many cancers, and many studies have begun to pay attention to the detection of anti-p53 antibodies in HCC. The purpose of this study is to quantitatively and comprehensively analyze the potential diagnostic value of anti-p53 autoantibodies in HCC METHODS:: English articles up to November 2019 were collected. The overall sensitivity and specificity were calculated. Besides, the positive likelihood ratio, negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curves of the overall diagnostic accuracy of anti-p53 antibody were calculated by STATA software. Finally, according to the heterogeneity of the results, the subgroup analysis, and the publication bias were performed. RESULTS: A total of 16 eligible studies were incorporated into this meta-analysis, including 1323 patients with HCC and 1896 control. The pooled sensitivity was 0.28(0.17-0.41) and specificity was 0.98 (0.95-0.99). The pooled DOR was 10.44 (6.31-17.29) and the pooled NLR was 0.74 (0.63-0.86). The area under ROC curve of symmetrical ROC was 0.840. CONCLUSIONS: The anti-p53 antibody has a high specificity for HCC, but the low sensitivity is not perfect and would limit the clinical application. The anti-p53 antibody would help rule out HCC but not help rule in HCC for early diagnosis. Whether combined as a diagnostic panel with other biomarkers or laboratory tests may prove useful requires further study.


Assuntos
Anticorpos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/antagonistas & inibidores
8.
Medicine (Baltimore) ; 99(34): e21952, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846865

RESUMO

BACKGROUND: Sodium cantharidinate/vitamin B6 (SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.


Assuntos
Cantaridina/análogos & derivados , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/patologia , Vitamina B 6/farmacologia , Complexo Vitamínico B/farmacologia , Cantaridina/administração & dosagem , Cantaridina/farmacologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/psicologia , China/epidemiologia , Quimioterapia Combinada/métodos , Humanos , Sistema Imunitário/efeitos dos fármacos , Injeções/métodos , Fígado/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Sobrevida , Resultado do Tratamento , Vitamina B 6/administração & dosagem , Complexo Vitamínico B/administração & dosagem
9.
PLoS One ; 15(8): e0238078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845895

RESUMO

BACKGROUNDS AND AIMS: Because of the known limitations of ultrasonography (US) alone, we re-evaluated whether complimentary testing for serum alpha-fetoprotein (AFP) is helpful in surveilling for hepatocellular carcinoma (HCC) in high-risk populations. METHODS: We included, from a hospital-based cancer registry, 1,776 asymptomatic adults who were surveilled biannually with the AFP test and US and eventually diagnosed with HCC between 2007 and 2015. Based on the screening results, these patients were divided into three groups: AFP (positive for AFP only; n = 298 [16.8%]), US (positive for US only; n = 978 [55.0%]), and AFP+US (positive for both; n = 500 [28.2%]). We compared the outcomes of the three groups, calculating the survival of the AFP group both as observed survival and as survival corrected for lead-time. RESULTS: In terms of tumor-related factors, the separate AFP and US groups were more likely to have early stage HCC and to receive curative treatments than the combined AFP+US group (Ps<0.05). The AFP group had significantly better overall and cancer-specific survival than the AFP+US group after adjusting for covariates (adjusted hazard ratios [HRs] 0.68 and 0.62, respectively). In analyses correcting for lead-time in the AFP group (doubling time 120 days), the respective adjusted HRs for the AFP group were unchanged (0.74 and 0.67), but they were no longer significant after additional adjustment for tumor stage and curative treatment (0.87 and 0.81). CONCLUSIONS: HCC cases detected by the AFP test without abnormal ultrasonic findings appear to have better survival, possibly as a result of stage migration and the resulting cures. Complementary AFP surveillance, together with US, could be helpful for at-risk patients.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Detecção Precoce de Câncer , Feminino , Hepatite B/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Ultrassonografia
10.
Medicine (Baltimore) ; 99(32): e21489, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769883

RESUMO

For the treatment of huge unresectable hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) or transcatheter arterial embolization (TAE) generally had poor effects and high complication rates. Our previous study found that Hepatic arterial infusion chemotherapy (HAIC) is a safe procedure and provides better survival than symptomatic treatment for the patients with huge unresectable HCC. The aim of the study is to compare the effect of HAIC vs TAE in patients with huge unresectable HCC.Since 2000 to 2005, patients with huge (size > 8 cm) unresectable HCC were enrolled. Twenty-six patients received HAIC and 25 patients received TAE. Each patient in the HAIC group received 2.5 + 1.4 (range: 1-6) courses of HAIC and in the TAE group received 1.8 + 1.2 (range: 1-5) courses of TAE. Baseline characteristics and survival were compared between the HAIC and TAE group.The HAIC group and the TAE group were similar in baseline characteristics and tumor stages. The overall survival rates at 1 and 2 years were 42% and 31% in the HAIC group and 28% and 24% in the TAE group. The patients in the HAIC group had higher overall survival than the TAE group (P = .077). Cox-regression multivariate analysis revealed that HAIC is the significant factor associated with overall survival (relative risk: 0.461, 95% confidence interval: 0.218-0.852, P = .027). No patients died of the complications of HAIC but three patients (12%) died of the complications of TAE.In conclusion, HAIC is a safe procedure and provides better survival than TAE for patients with huge unresectable HCCs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/mortalidade , Infusões Intra-Arteriais/mortalidade , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Embolização Terapêutica/métodos , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Análise de Regressão , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(32): e21561, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769898

RESUMO

In this study, we evaluated the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).This retrospective study evaluated 139 patients with BCLC stage C HCC who underwent CyberKnife SBRT between January 2009 and September 2017. All patients had BCLC-C, Child-Turcotte-Pugh score A-B. In-field control, overall survival (OS), progression free survival (PFS), and prognostic factors were evaluated.An objective response rate was achieved in 81.5% patients (complete response, 36.2%, partial response, 45.3%). The median survival was 15.44 months, and the 1-, 3-, 5-year OS rates were 56%, 28%, and 20%, respectively. The median PFS was 6 months, the PFS rate at 1-, 3-, and 5-year were 35%, 14%, and 10%, respectively. In-field control of 1 to 2 years was achieved in 85.1% of patients. The major pattern of failure was out-field intrahepatic failure which comprised 42.9% of patients. Multivariate analysis revealed that the Child-Turcotte-Pugh score, macrovascular invasion, advance stage (III-IV), and tumor response rate were independent predictors of OS.The result of our study shows that SBRT is a safe and effective therapeutic option for BCLC stage C HCC lesions that are unsuitable for standard loco-regional therapies, Moreover, SBRT has acceptable local control rates and low-treatment toxicity.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirurgia/mortalidade , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Radiocirurgia/métodos , Estudos Retrospectivos , Taxa de Sobrevida
12.
PLoS One ; 15(7): e0235576, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614912

RESUMO

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels. METHODS: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence. RESULTS: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5. CONCLUSION: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
13.
Medicine (Baltimore) ; 99(27): e20919, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629689

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide; its morbidity and mortality have both recently increased. Lately, the role played by the neutrophil-lymphocyte ratio (NLR) in the development of HCC has attracted attention. However, the exact relationship is not fully understood.A total of 538 participants diagnosed with HCC were recruited between 2010 and 2018. Their relevant routine blood parameters were measured, including NLR. Pearson Chi-Squared test, Spearman Rho test, and logistic regression analysis were performed to explore any correlations between NLR and HCC. A receiver operating characteristic (ROC) curve analysis was performed to determine the usefulness of NLR for predicting HCC. Univariate and multivariate Cox regression analysis for relevant routine blood parameters and any relationships with overall survival (OS) were performed. The Kaplan-Meier method was used to explore any further relationships with OS.NLR was significantly correlated with HCC tumor size by Pearson Chi-Squared test (P = .008). Furthermore, Spearman correlation coefficient showed that HCC tumor size was significantly correlated with NLR (P = .115, P = .008). NLR could sensitively and specifically predict HCC tumor size (area under the curve [AUC], 0.605; 95% confidence interval [CI], 0.429-0.743; P = .000). Higher NLR in patients with HCC was correlated with better OS (hazard ratio [HR] = 0.584; P = .000).A close correlation existed between increased NLR and HCC; NLR could sensitively and specifically predict HCC. High NLR might be an independent protective factor in the prognosis of patients with HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Linfócitos , Recidiva Local de Neoplasia/mortalidade , Neutrófilos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , China , Feminino , Humanos , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Análise de Sobrevida , Adulto Jovem
14.
Anticancer Res ; 40(7): 3983-3990, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620641

RESUMO

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.


Assuntos
Carcinoma Hepatocelular/patologia , Veias Hepáticas/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Life Sci ; 257: 118131, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32710948

RESUMO

AIMS: ATP-binding cassette (ABC) transporters constitute one of the largest families of membrane proteins in most organisms; however, their functions in hepatocellular carcinoma (HCC) remain unclear. MAIN METHODS: A set of bioinformatic tools was integrated to analyze the expression of 49 members of the ABC transporter family. The function of members which had prognostic values in HCC was explored by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. KEY FINDINGS: ABCA8 and ABCA9 were significantly down-regulated in HCC. Prognostic analysis indicated that HCC patients with low expression of ABCA8 and ABCA9 had significantly shorter survival time. On the contrary, ABCB6 was over-expressed in the disease and high expression of ABCB6 was associated with worse prognosis. Co-expression analysis, and subsequently GO and KEGG analysis indicated that ABCA8 and ABCA9 might participate in the catabolic processes of multiple metabolites, while ABCB6 might regulate ferroptosis. SIGNIFICANCE: This study reveals a previously unrecognized function of ABCB6 in HCC, by regulating ferroptosis. Since ABCB6 is over-expressed in HCC and ferroptosis involves in cancer development, ABCB6 might be a promising therapeutic target in the disease.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Carcinoma Hepatocelular/metabolismo , Ferroptose , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Prognóstico , Mapas de Interação de Proteínas , Análise de Sobrevida
16.
Am Surg ; 86(7): 865-872, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32721171

RESUMO

BACKGROUND: Hepatitis C virus (HCV) has historically been the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States. With improved HCV treatment, cirrhosis secondary to other etiologies is increasing. Given this changing epidemiology, our aim was to determine the impact of cirrhosis etiology on overall survival (OS) in patients with HCC. METHODS: All patients with cirrhosis and primary HCC from the US Safety Net Collaborative (2012-2014) database were included. Patients were grouped into "safety net" and "academic" based on where they received their care. The primary outcome was the OS. RESULTS: 1479 patients were included. The average age was 60 years and 78% (n = 1156) were male. 56% (n = 649) received care at academic and 44% (n = 649) at safety net hospitals. The median model for end-stage liver disease (MELD) was 10 (IQR 8-16). Median OS was 23 months. Etiology of cirrhosis was viral hepatitis 56% (n = 612), alcohol abuse 14% (n = 152), alcohol and hepatitis 23% (n = 251), and other 7% (n = 85). Patients with alcohol-related cirrhosis (alcohol alone or with hepatitis) were younger (59 vs 62 years), more likely to be male (86% vs 75%), treated at a safety net facility (45% vs 35%), uninsured (17% vs 13%), and had a higher MELD (median 12 vs 10) (all P < .003). They were less likely to have been screened for HCC within 1 year of diagnosis (20% vs 29%) and to receive treatment (69% vs 81%), and more likely to present with stage IV disease (21% vs 15%) (all P < .001). Patients with alcohol-related cirrhosis had decreased OS (5-year OS 24% vs 40%, P < .001), which persisted in a subset analysis of both academic and safety net populations. CONCLUSION: Although not significant on MVA, alcohol-related cirrhosis is associated with all factors that correlate with decreased survival from HCC. Efforts must focus on this vulnerable patient population to optimize screening, treatment, and outcomes.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Provedores de Redes de Segurança/estatística & dados numéricos , Idoso , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
17.
Medicine (Baltimore) ; 99(28): e21161, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664152

RESUMO

In this study, we investigated the long-term survival of patients with hepatocellular carcinoma (HCC) after conventional treatment other than liver transplantation (LT) in our institute and discuss the limitation of non-transplant treatment for HCC and the proper indictors of LT in the recent comprehensive era.Between 2003 and 2016, 181 patients with HCC aged ≦70 years received active treatment including liver resection, radiofrequency ablation (RFA), and transcatheter arterial chemoembolization (TACE). We analyzed the factors associated with overall survival and proposed new priority for the indicators of LT in HCC patients according to the extracted factors by comparing the survival with 39 transplanted patients with HCC.Child-Turcotte-Pugh (CTP) score (HR: 1.276; 95% CI: 1.049-1.552, P = .015), and number of tumors (HR: 1.238; 95% CI: 1.112-1.377, P < .001) were selected as significant factors associated with the survival after active treatments for HCC. Patients with LT had significantly better long-term survival compared with those with non-transplant patients regardless of aforementioned factors. However, regarding relatively short survival (3 years), patients with CTP score of ≧9 and/or ≧3 tumors with non-transplant treatment had poorer survival compared with those of transplanted patients (P < .05).We propose that CTP score of 9 and/or 3 tumors before non-transplant, intensive treatment might be a new priority for considering indicators of LT in patients with HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Ablação por Cateter/mortalidade , Quimioembolização Terapêutica/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
18.
Medicine (Baltimore) ; 99(29): e20962, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702836

RESUMO

BACKGROUND: Trans-catheter arterial chemoembolization (TACE) plus Sorafenib is recommended as one of the primary means for treating hepatocellular carcinoma (HCC). This updated meta-analysis focuses on identifying the efficacy and safety of TACE plus Sorafenib versus TACE, which remains controversial despite years of exploration. METHOD: PubMed, Medline, Embase, China Journal Full-text Database, Wanfang Database, and Weipu Database were used to retrieve the studies which are about comparing the clinical efficacy and safety of TACE+Sorafenib with TACE alone. The Review Manager (Version 5. 3) software was used to perform a meta-analysis of the results of studies which met the inclusion criteria recommended by the Cochrane Collaboration. RESULT: Compared with TACE for treating primary HCC, TACE combined with Sorafenib can improve the 1 year, 2 years, 3 years, and 5 years overall survival rate (OS) of patients, respectively, and also improve disease control rate (DCR) and objective response rate (ORR). In terms of adverse reactions, the treatment group can lead to more complications significantly, such as hand-foot skin reaction, hypertension, diarrhea, rash, hair loss, and so on, most of which are relevant to Sorafenib related adverse reactions, but most patients have a good prognosis after symptomatic treatment. CONCLUSION: The clinical efficacy of TACE combined with Sorafenib in treating primary hepatocellular carcinoma is better than TACE, and the safety is acceptable.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/mortalidade
19.
PLoS One ; 15(6): e0234726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559205

RESUMO

Hepatocellular carcinoma (HCC), the most malignant form of primary liver cancer, is the fourth most prevalent cause of cancer mortality globally. It was recently discovered that the dietary fermentable fiber, inulin, can reprogram the murine liver to favor HCC development in a gut microbiota-dependent manner. Determining the molecular pathways that are either over expressed or repressed during inulin-induced HCC would provide a platform of potential therapeutic targets. In the present study, we have combined analysis of the novel inulin-induced HCC murine model and human HCC samples to identify differentially expressed genes (DEGs) in hepatocarcinogenesis. Hepatic transcriptome profiling revealed that there were 674 DEGs in HCC mice compared to mice safeguarded from HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis uncovered enrichment in ECM-receptor interaction, steroid hormone biosynthesis, PPAR signaling pathway, focal adhesion and protein digestion and absorption during inulin-induced HCC. Tandem mass tag based quantitative, multiplexed proteomic analysis delineated 57 differentially expressed proteins, where the over-expressed proteins were associated with cell adhesion molecules, valine, leucine and isoleucine degradation and ECM-receptor interaction. After obtaining the human orthologs of the mouse genes, we did a comparison analysis to level 3 RNA-seq data found in the Cancer Genome Atlas (TCGA) database, corresponding to human HCC (n = 361) and healthy liver (n = 50) samples. Out of the 549 up-regulated and 68 down-regulated human orthologs identified, 142 genes (137 significantly over-expressed and 5 significantly under-expressed) were associated with human HCC. Using univariate survival analysis, we found 27 over-expressed genes involved in cell-cell adhesion and cell division that were associated with poor HCC patient survival. Overall, the genetic and proteomics signatures highlight potential underlying mechanisms in inulin-induced HCC and support that this murine HCC model is human relevant.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Moléculas de Adesão Celular/metabolismo , Modelos Animais de Doenças , Ontologia Genética , Humanos , Insulina/toxicidade , Estimativa de Kaplan-Meier , Fígado/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Proteômica , Transdução de Sinais , Receptor 5 Toll-Like/deficiência , Receptor 5 Toll-Like/genética , Transcriptoma
20.
Medicine (Baltimore) ; 99(23): e20321, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501978

RESUMO

BACKGROUND: In recent years, there has been considerable uncertainty about the optimal treatment option for very early hepatocellular carcinoma (HCC) with tumor size less than 2 cm. Therefore, we performed a systematic review and meta-analysis to evaluate the outcomes of the different treatments. METHODS: This study was designed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). PubMed, EMBASE, and Cochrane library were searched for calculating the survival rates, and the "time to event" method was used to compare the outcomes of liver resection (LR) and radiofrequency ablation (RFA). All studies focusing on the treatment of solitary HCC up to 2 cm by different techniques were included in our analysis. The Hazard ratios (HR) and 95% confidence intervals (CI) derived from multivariate and univariate analysis were utilized to assess the treatment risks. RESULTS: We included 32 studies in our systematic review. The median 5-year overall survival (OS) and recurrence-free survival rate (RFS) for LR were 73% and 47%, respectively, and those for RFA were 73% and 43%, respectively. RFA was found to be associated with increased risk of mortality and recurrence compared to LR (HR = 1.61, 95% CI: 1.35-1.92, P < .0001 for OS and HR = 1.75, 95% CI: 1.56-1.96, P < .0001 for RFS). CONCLUSION: Our meta-analysis demonstrated that LR is superior to RFA in the treatment of solitary HCC up to 2 cm, with reduction in mortality and recurrence risk and improved long-term outcome.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/mortalidade , Ablação por Cateter/efeitos adversos , Hepatectomia/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Carga Tumoral
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