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1.
Front Oncol ; 11: 737497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745958

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

3.
Eur J Surg Oncol ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34838392

RESUMO

PURPOSE: Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). PATIENTS AND METHODS: From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). RESULTS: Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P= 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P= 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001). CONCLUSION: Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

4.
J Clin Transl Hepatol ; 9(5): 661-671, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722181

RESUMO

Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34559308

RESUMO

BACKGROUND: Lenvatinib is regarded as the first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of lenvatinib with or without immune checkpoint inhibitors (ICIs) in patients with unresectable HCC. METHODS: In this multicentric retrospective study, patients with unresectable HCC who treated with lenvatinib with or without ICIs would be enrolled. Overall survival, progression-free survival, objective response rate, and disease control rate were calculated to assess the antitumor response. RESULTS: Between January 2019 and August 2020, 65 patients received lenvatinib plus ICIs while other 45 patients received lenvatinib. The baseline characteristics were comparable between the two groups. Lenvatinib plus ICIs provided significantly higher overall survival (hazard ratio = 0.47, 95% CI 0.26-0.85; p = 0.013) and progression-free survival (hazard ratio = 0.35, 95% CI 0.20-0.63; p < 0.001) than lenvatinib monotherapy. Moreover, patients with lenvatinib plus ICIs had significantly higher objective response rate (41.5% vs 20.0%, p = 0.023) and disease control rate (72.3% vs 46.7%, p = 0.009) per RECIST v1.1 than those with lenvatinib. No treatment-related deaths were observed. Grade 3 or greater adverse events occurring in 10% or more of patients in either treatment group were hypertension [13 (20.0%) of 65 patients treated with lenvatinib plus ICIs vs 8 (17.8%) of 45 patients treated with lenvatinib], and palmar-plantar erythrodysesthesia [seven (10.8%) vs two (4.4%)]. CONCLUSIONS: In this real-world study, lenvatinib combined with ICIs showed significantly promising efficacy and manageable safety than lenvatinib alone in patients with unresectable HCC.

6.
Front Oncol ; 11: 700228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395268

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC). Methods: Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM. Results: Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081). Conclusion: Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

7.
Cancer Cell Int ; 21(1): 422, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376192

RESUMO

BACKGROUND: Epithelial-mesenchymal transition (EMT) promotes migration, invasion, and metastasis of hepatocellular carcinoma (HCC) cells. The molecular mechanisms behind EMT and metastasis in HCC remain unclear. METHODS: Microarray analysis was used to identify lncRNAs expression during polarization of U937 macrophages from M2 to M1 phenotype. The expression of the identified lncRNA was compared between clinical samples of HCC tissues or adjacent normal tissues, as well as between HCC and normal liver cell lines. lnc-Ma301 was overexpressed or knocked-down in HCC cell lines, and the effects were assessed in vitro and in vivo. Interactions among lnc-Ma301 and its potential downstream targets caprin-1 were investigated in HCC cell lines. Effects of lnc-Ma301 over- and underexpression on the Akt/Erk1 signaling pathways were examined. RESULTS: Microarray analyses identified lnc-Ma301 as one of the most overexpressed long non-coding RNAs during polarization of U937 macrophages from M2 to M1 phenotype. Lnc-Ma301 showed lower expression in HCC tissues than in adjacent normal tissues, and lower expression was associated with worse prognosis. Activation of lnc-Ma301 inhibited cell proliferation, migration and EMT in HCC cell cultures, and it inhibited lung metastasis of HCC tumors in mice. Mechanistic studies suggested that lnc-Ma301 interacts with caprin-1 to inhibit HCC metastasis and EMT through Akt/Erk1 pathway. CONCLUSIONS: Lnc-Ma301 may help regulate onset and metastasis of HCC.

8.
Biosci Rep ; 41(4)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33835138

RESUMO

OBJECTIVE: The present study aimed to identify risk factors for overall survival in advanced hepatocellular carcinoma (HCC) patients and establish a scoring system to select patients who would benefit from hepatic resection. METHODS: Survival curves were analyzed using the Kaplan-Meier method and log-rank test. The prognostic scoring system was developed from training cohort using a Cox-regression model and validated in a external validation cohort Results: There were 401 patients in the training cohort, 163 patients in the external validation cohorts. The training cohort median survival in all patients was 12 ± 1.07 months, rate of overall survival was 49.6% at 1 year, 25.0% at 3 years, and 18.0% at 5 years. A prognostic scoring system was established based on age, body mass index, alkaline phosphatase, tumor number and tumor capsule. Patients were classified as low- risk group(≤3.5) or high-risk group(>3.5). High-risk patients had a median survival of 9 months, compared with 23 months in low-risk patients. The area under the receiver operating characteristic curve (AUC) of the prognostic scoring system was 0.747 (0.694-0.801), which is significantly better than AFP, Child-Pugh and ALBI. The AUC of validation cohorts was 0.716 (0.63-0.803). CONCLUSION: A prognostic scoring system for hepatic resection in advanced HCC patients has been developed based entirely on preoperative variables. Patients classified as low risk using this system may experience better prognosis after hepatic resection.

9.
Hepatol Int ; 15(1): 114-126, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33495903

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) and microvascular invasion (MVI) are types of intrahepatic vascular metastasis of hepatocellular carcinoma (HCC) and are highly correlated with poor prognosis. However, the underlying biomarkers of PVTT and MVI are unclear. METHODS: We identified a PVTT/MVI-associated gene S100P by cDNA microarray analysis, and assess the potential value of serum S100P measurement in the differential diagnosis of HCC and prediction of MVI status with large retrospective and perspective cohort studies. RESULTS: The mRNA and protein of S100P was increased in HCCs with PVTT or MVI. High S100P immunostaining in tumors was correlated with inferior tumor-free survival. Serum S100P values discriminated patients with HCCs from those with benign liver tumors, and it showed predictive potential of MVI status in both retrospective and perspective cohorts. S100P may regulate HCC tumorigenicity and invasive ability; S100P also was associated with up-regulation of CD44, which may mediate HCC cell adhesion to form PVTT/MVI. CONCLUSIONS: Serum S100P may be a novel differential diagnostic marker for HCC and a potential predictor of MVI status pre-surgery for HCC patients. S100P overexpression in HCC is highly correlated with the formation of PVTT and MVI, which may make S100P as a potential therapeutic target for HCC metastasis.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Neoplasias/metabolismo , Trombose , Biomarcadores , Proteínas de Ligação ao Cálcio/genética , Carcinoma Hepatocelular/complicações , Humanos , Neoplasias Hepáticas/complicações , Invasividade Neoplásica , Veia Porta , Prognóstico , Estudos Retrospectivos , Trombose/etiologia
10.
Surgery ; 169(4): 911-920, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31879090

RESUMO

BACKGROUND: Repeat hepatectomy is a feasible treatment modality for intrahepatic recurrence after hepatectomy of hepatocellular carcinoma, yet the survival benefit remains ill-defined. The objective of the current study was to define long-term, oncologic outcomes after repeat hepatectomy among patients with early and late recurrence. METHODS: Patients undergoing curative-intent repeat hepatectomy for recurrent hepatocellular carcinoma were identified using a multi-intuitional database. Early and late recurrence was defined by setting 1 year after initial hepatectomy as the cutoff value. Patient clinical characteristics, overall survival, and disease-free survival were compared among patients with early and late recurrence before and after propensity score matching. RESULTS: Among all the patients, 81 had early recurrence and 129 had late recurrence from which 74 matched pairs were included in the propensity score matching analytic cohort. Before propensity score matching, 5-year overall survival and disease-free survival after resection of an early recurrence were 41.7% and 17.9%, respectively, which were worse compared with patients who had resection of a late recurrence (57.0% and 39.4%, both P < .01). After propensity score matching, 5-year overall survival and disease-free survival among patients with early recurrence were worse compared with patients with late recurrence (41.0% and 19.2% vs 64.3% and 43.2%, both P < .01). After adjustment for other confounding factors on multivariable Cox-regression analysis, early recurrence remained independently associated with decreased overall survival and disease-free survival (hazard ratio 2.22, 95% confidence interval 1.35-3.34, P = .001; hazard ratio 1.86, 95% confidence 1.26-2.74, P = .002). CONCLUSION: Repeat hepatectomy for early recurrence was associated with worse overall survival and disease-free survival compared with late recurrence. These data may help inform patients and selection of patients being considered for repeat hepatectomy of recurrent hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Reoperação , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Seguimentos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Reoperação/métodos , Resultado do Tratamento
13.
J Cancer ; 11(21): 6437-6444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33033527

RESUMO

Objective: To explore the effect of COX-2 inhibitor celecoxib in combination with metformin on the prevention of Hepatocellular carcinoma (HCC) and the mechanisms involved. Methods: HCC cell lines and an HCC rat model were treated with celecoxib, metformin or a combination of both. Cell viability and tumor formation were measured. Results: In vitro and in vivo studies showed that treatment with a combination of celecoxib and metformin inhibited proliferation of HCC to a greater extent than either treatment alone, by reducing the phosphorylation of MTOR. Conclusion: The study suggested that celecoxib combined with metformin would be more effective for the preventing occurrence of HCC than either treatment alone and this combination of therapy is worthy of further study.

14.
J Clin Transl Hepatol ; 8(3): 285-291, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083251

RESUMO

Background and Aims: This study was designed to analyze the effects of age and clinicopathological characteristics on prognosis of Chinese patients with hepatocellular carcinoma (HCC). Methods: The clinical data of 2032 HCC patients who were first diagnosed with HCC and underwent curative hepatectomy in our hospital between January 2006 and January 2011 were retrospectively analyzed. Results: Younger HCC patients (age <40 years, n=465) had a significantly higher hepatitis B infection rate, larger tumors, higher alpha-fetoprotein levels, higher preoperative liver function, and more frequent vascular invasions than older patients. Most younger patients were suitable for anatomical hepatectomy, and their tumors were found to be at a highly advanced stage. The recurrence-free survival and overall survival rates of younger HCC patients were significantly worse than those of older patients but this difference disappeared after propensity score matching. Multivariate analysis of pre-matched samples showed that age ≤40 years was one of the independent risk factors associated with poor overall survival. Conclusions: Younger patients showed different clinicopathological characteristics than older patients, such as higher rates of hepatitis B infection and advanced tumors. The recurrence-free survival and overall survival rates of younger HCC patients after hepatectomy may be similar to those of older patients.

15.
Expert Rev Gastroenterol Hepatol ; 14(8): 749-756, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32552297

RESUMO

OBJECTIVE: To investigate the effect of perioperative antiviral therapy on the prognosis of hepatitis B virus (HBV) DNA-negative patients with HBV-related hepatocellular carcinoma (HCC). METHODS: The clinical data of 140 patients who were positive for hepatitis B surface antigen (HBsAg) but negative for HBV DNA before partial hepatectomy were retrospectively analyzed. Propensity score matching (PSM) was used to eliminate the influence of confounding factors on prognosis. Postoperative liver function, HBV reactivation rate, recurrence-free survival (RFS) and overall survival (OS) were compared between antiviral and non-antiviral therapy groups. RESULTS: Compared with the non-antiviral therapy group, the antiviral therapy group had a lower rate of HBV reactivation and better postoperative liver function (P < 0.05). The 1-year, 2-year and 3-year survival rates of the antiviral therapy group were better than those of the non-antiviral therapy group before or after PSM (P < 0.05). Prognostic analysis excluding 11 patients with HBV reactivation showed that perioperative antiviral therapy could significantly improve OS (P = 0.004), but had no significant effect on RFS (P = 0.056). Multivariate analyzes showed that antiviral therapy was associated with better OS. CONCLUSION: Perioperative antiviral therapy can significantly reduce the risk of HBV reactivation and improve postoperative liver function, RFS and OS.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/cirurgia , DNA Viral/sangue , Vírus da Hepatite B , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatectomia , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/fisiopatologia , Humanos , Fígado/fisiopatologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Período Pós-Operatório , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Ativação Viral
16.
Biosci Rep ; 40(6)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32478394

RESUMO

BACKGROUND AND AIM: Assessing the average survival rate of patients with hepatocellular carcinoma (HCC) after hepatectomy is important for making critical decisions in everyday clinical practice. The present study aims to develop and validate a nomogram for assessing the overall survival probability for such patients. METHODS: The putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression and model selection based on the Akaike information criterion. The nomogram was subjected to internal and external validation. The nomogram endpoints were death within 1, 3, and 5 years. RESULTS: A consecutive sample of 522 HCC patients who underwent potentially curative hepatectomy was retrospectively analyzed. Age, Barcelona clinic liver cancer (BCLC) stage, tumor size, alanine transaminase, alpha fetal protein, and serum prealbumin were included in the final model. The nomogram's discriminative ability was good in the training set (C-index was 0.74 for 1 year, 0.73 for 3 years, 0.70 for 5 years) and was validated using both an internal bootstrap method (C-index was 0.73 for 1 year, 0.72 for 3 years, 0.69 for 5 years) and an external validating set (C-index was 0.72 for 1 year, 0.72 for 3 years, 0.69 for 5 years). The calibration plots for the endpoints showed optimal agreement between the nomogram's assessment and actual observations. CONCLUSIONS: The nomogram (an Excel-based tool) can be useful for assessing the probability of survival at 1, 3, and 5 years in patients with HCC after hepatectomy.


Assuntos
Carcinoma Hepatocelular/cirurgia , Técnicas de Apoio para a Decisão , Hepatectomia , Neoplasias Hepáticas/cirurgia , Nomogramas , Adulto , Fatores Etários , Alanina Transaminase/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Tomada de Decisão Clínica , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pré-Albumina/análise , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/análise
17.
J Cancer ; 11(11): 3400-3406, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231746

RESUMO

Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is associated with high rate of post-operative recurrence and low rate of survival, which may reflect the post-operative persistence of cancer stem cells (CSCs). Here we explored the potential correlation between DPHCC and expression of CSCs markers. Methods: In this retrospective study, we included 19 patients with DPHCC and 61 patients with non-DPHCC treated in 2015 by liver resection. Paraffin-embedded tumor tissue specimens were analyzed using immunohistochemistry as well as immunofluorescence double-staining. Rates of recurrence-free survival and overall survival were compared between the two groups using the Kaplan-Meier method, and expression of the CSC markers CD133, CD90, and EpCAM were compared using real-time quantitative PCR and western blotting. Results: Overall survival rates were significantly lower for patients with DPHCC than patients with non-DPHCC at 1 year (78.9% vs 93.4%), 2 years (52.6% vs 72.1%), and 3 years (42.1% vs 67.2%) (P = 0.019). Multivariate Cox proportional hazard modeling identified CK19 positivity (P = 0.016) and multiple nodules (P = 0.023) as independent predictors of poor recurrence-free survival. Independent predictors of poor overall survival were CK19 positivity (P = 0.032), Barcelona Clinic Liver Cancer stage C (P = 0.025) and carbohydrate antigen 19-9 (CA19-9) >37 ng/ml (P = 0.016). Expression of CD133 and EpCAM mRNA and protein were significantly higher in DPHCC tissue than non-DPHCC tissue, while CD90 expression was similar between the groups. Conclusions: These results suggest that DPHCC is associated with significantly lower overall survival than non-DPHCC, and that the poor prognosis among DPHCC patients may be related to the presence of CSCs expressing CD133 and EpCAM.

18.
Ann Surg ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32097166

RESUMO

OBJECTIVE: To develop a nomogram to estimate the risk of SPLD (International Study Group of Liver Surgery definition grade B or C) and long-term survival in patients with HCC before hepatectomy. BACKGROUND: SPLD is the leading cause of post-hepatectomy mortality. The decision to refer an HCC patient for hepatectomy is mainly based on the survival benefit and SPLD risk. Prediction of SPLD risk before hepatectomy is of great significance. METHODS: A total of 2071 consecutive patients undergoing hepatectomy for HCC were recruited and randomly divided into the development cohort (n = 1036) and internal validation cohort (n = 1035). Five hundred ninety patients from another center were enrolled as the external validation cohort. A nomogram was developed based on independent preoperative predictors of SPLD determined in multivariable logistic regression analysis. RESULTS: The SPLD incidences in the development, internal, and external validation cohorts were 10.1%, 9.5%, and 8.6%, respectively. Multivariable analysis identified total bilirubin, albumin, gamma-glutamyl transpeptidase, prothrombin time, clinically significant portal hypertension, and major resection as independent predictors for SPLD. Incorporating these variables, the nomogram showed good concordance statistics of 0.883, 0.851, and 0.856, respectively in predicting SPLD in the 3 cohorts. Its predictive performance in SPLD, 90-day mortality, and overall survival (OS) outperformed Child-Pugh, model for end-stage liver disease, albumin-bilirubin, and European Association for the Study of the Liver recommended algorithm. With a nomogram score of 137, patients were stratified into low and high risk of SPLD. High-risk patients also had decreased OS. CONCLUSIONS: The nomogram showed good performance in predicting both SPLD and OS. It could help surgeons select suitable HCC patients for hepatectomy.

19.
J Cell Physiol ; 235(2): 1090-1102, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31256427

RESUMO

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepatócitos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Prognóstico , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética
20.
Ann Med ; 52(1-2): 21-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31876201

RESUMO

Background and aims: Hepatic resection is the first-line treatment for hepatocellular carcinoma (HCC). Whether to perform anatomical (AR) or non-anatomical resection (NAR) remains controversial. This retrospective study compares the outcomes according to the number and type of circulating tumour cells (CTCs).Methods: The cohort included 136 patients with HCC treated with R0 resection between 2014 and 2017. CanPatrol CTC-enrichment technique was used to enrich and classify CTCs according to epithelial-to-mesenchymal transition phenotype.Results: 91.91% of total patients were CTC-positive, with 91.23% in the AR group and 92.41% in the NAR group. Tumour-free survival (TFS) did not differ significantly between the two groups. However, TFS was significantly higher in patients with low CTCs count and mesenchymal- and epithelial/mesenchymal-negative phenotypes. As for the incidence and types of recurrence, high pre-resection CTC count and mesenchymal- and epithelial/mesenchymal-positivity were significantly associated with extrahepatic and multi-intrahepatic recurrence. Higher morbidities for hepatic failure and ascites were observed in patients treated by AR.Conclusion: AR may be more beneficial than NAR only in patients with low CTC count and mesenchymal- and epithelial/mesenchymal-negative phenotypes. For patients with a high CTC count, the balance between operative risk and prognostic benefit is more important than the resection method performed.Key messagesAnatomic resection may improve the survival of HCC patients, but only those with low CTC count and negative M- and E/M-CTC phenotypes.CTC analysis before surgery can be used to better guide the choice of resection method for HCC.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Feminino , Hepatectomia/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento
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