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1.
BMC Cancer ; 18(1): 621, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859044

RESUMO

BACKGROUND: It is essential to understand the mechanisms responsible for hepatocellular carcinoma (HCC) progression and chemoresistance in order to identify prognostic biomarkers as well as potential therapeutic avenues. Recent findings have shown that SLIT3 appears to function as a novel tumor suppressor gene in various types of cancers, yet its clinical correlation and role in HCC has not been understood clearly. METHODS: We determined the transcript levels of Slit3 in tumor and adjacent normal tissues within two cohorts (N = 40 and 25) of HCC patients, and correlated the gene expression with the clinicopathological data. Subsequently, the functional effects and underlying molecular mechanisms of Slit3 overexpression and/or repression were studied using cell-line and mouse models. RESULTS: Our results demonstrated a repression in Slit3 expression in nearly 50% of the HCC patients, while the overall expression of Slit3 inversely correlated with the size of the tumor in both cohorts of patients. Stable down-regulation of Slit3 in HCC cell-lines induced cell proliferation in vitro and tumor growth in vivo, while stable Slit3 overexpression repressed these effects. Molecular investigations showed that the stable Slit3 repression-induced cell proliferation was associated with a higher expression of ß-catenin and a repressed GSK3ß activity. Moreover, Slit3-repression induced chemoresistance to sorafenib, oxaliplatin and 5-FU through impairment of ß-catenin degradation and induction of cyclin D3 and survivin levels. The effects induced by stable Slit3-repression were diminished by transient repression of ß-catenin by siRNA approach. CONCLUSION: This study suggests that Slit3 acts as a tumor suppressor in HCC by repressing the tumor growth and thus tumor progression. Low Slit3 level indicates a poor response of HCC cells to chemotherapy. Restoration or overexpression of Slit3 is a potential therapeutic approach to repress the tumor growth and enhance the efficacy of chemotherapeutic agents.


Assuntos
Carcinoma Hepatocelular/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Genes Supressores de Tumor/fisiologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia
2.
Gut ; 66(8): 1496-1506, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27974549

RESUMO

OBJECTIVE: We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. DESIGN: We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. RESULTS: We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. CONCLUSIONS: Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Animais , Antibióticos Antineoplásicos/farmacologia , Proteína Axina/genética , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA , Feminino , Humanos , Neoplasias Hepáticas/química , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Taxa de Mutação , Transplante de Neoplasias , Proteínas Nucleares/genética , Transdução de Sinais , Sirolimo/farmacologia , Fatores de Transcrição/genética , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Ensaio Tumoral de Célula-Tronco , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/análise , Adulto Jovem , beta Catenina/genética
3.
Hepatology ; 64(3): 774-84, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27082062

RESUMO

UNLABELLED: Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8-4.2) months and 4.1 (2.8-4.3) months for dovitinib and sorafenib, respectively. Common any-cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar-plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0-13.8] and 5.7 [4.3-7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9-13.8] and 5.9 [5.0-7.6] months, respectively [P = 0.0002]). CONCLUSION: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774-784).


Assuntos
Antineoplásicos/uso terapêutico , Benzimidazóis/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Quinolonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Ásia Oriental/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/farmacocinética , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacocinética , Quinolonas/efeitos adversos , Quinolonas/farmacocinética , Sorafenibe , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Int J Mol Sci ; 18(6)2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28545226

RESUMO

Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples. We hypothesized that this subpopulation of cancer stem cells arises in the late stage of carcinogenesis from the bulk of tumor daughter cells which are CD26-. The manipulation of PIK3CA and TP53, two genes commonly deregulated in the late stage, had an effect on the maintenance of the CD26+ cell population. When CD26- tumor daughter cells were sorted and cultured, the emergence of tumor spheres containing CD26+ cells occurred. These findings shed light to the origin of colorectal cancer stem cells with metastatic properties, which has an implication on conventional treatments by surgery or adjuvant chemotherapy for tumor debulking.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Dipeptidil Peptidase 4/metabolismo , Células-Tronco Neoplásicas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/patologia , Feminino , Humanos , Masculino
5.
J Hepatol ; 65(2): 296-304, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27130844

RESUMO

BACKGROUND & AIMS: The purpose of this study was to determine whether biomarkers from baseline plasma and archival tissue specimens collected from patients enrolled in the EVOLVE-1 trial - a randomized phase 3 study of everolimus in hepatocellular carcinoma (HCC) - were associated with prognosis, etiology or ethnicity. METHODS: Circulating plasma levels of bFGF, PLGF, VEGF, VEGF-D, c-Kit, collagen IV, sVEGFR1 and VEGFR2 were measured by ELISA (N=503). Protein levels of IGF-1R, c-Met, mTOR, Tsc2 were assayed by immunohistochemistry (N=125). Genomic DNA sequencing was conducted on a panel of 287 cancer-related genes (N=69). RESULTS: Patients with baseline plasma concentrations of VEGF or sVEGFR1 above the cohort median had significantly shorter overall survival. These plasma biomarkers retained prognostic significance in a multivariate Cox regression model with geographic region, macroscopic vascular invasion and alpha fetoprotein AFP levels. Membranous c-Met protein levels were significantly lower for Asian patients, as well as for hepatitis B viral etiology. The prevalence of genetic changes were similar to previous reports, along with a trend towards higher PTEN and TSC2 mutations among Asians. CONCLUSIONS: The angiogenesis biomarkers VEGF and sVEGFR1 were independent prognostic predictors of survival in patients with advanced HCC. Potential differences in c-Met and mTOR pathway activation between Asian and non-Asian patients should be considered in future clinical trials. LAY SUMMARY: Our study demonstrates that circulating angiogenesis biomarkers can predict the survival outcome in patients with advanced hepatocellular carcinoma independent of the clinical variables. There is etiology and ethnicity variation in molecular pathway activation in hepatocellular carcinoma, which should be considered for future clinical trial design of targeted therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT01035229.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Humanos , Proteínas Proto-Oncogênicas c-met , Fator D de Crescimento do Endotélio Vascular
6.
N Engl J Med ; 368(24): 2266-76, 2013 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-23758232

RESUMO

BACKGROUND: Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. METHODS: We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. RESULTS: SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. CONCLUSIONS: SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.).


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Fatores de Transcrição/genética , Adulto , Animais , Carcinoma Hepatocelular/genética , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Redes e Vias Metabólicas/fisiologia , Camundongos , Camundongos Endogâmicos , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Transplante Heterólogo , Células Tumorais Cultivadas
7.
Genome Res ; 23(9): 1422-33, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23788652

RESUMO

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.


Assuntos
Carcinoma Hepatocelular/genética , Genoma Humano , Neoplasias Hepáticas/genética , Mutação , Sequência de Aminoácidos , Carcinoma Hepatocelular/virologia , DNA Viral/genética , Feminino , Vírus da Hepatite B/genética , Humanos , Janus Quinase 1/genética , Neoplasias Hepáticas/virologia , Masculino , Dados de Sequência Molecular , Fatores de Transcrição STAT/genética , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , Integração Viral , Via de Sinalização Wnt/genética , beta Catenina/genética
8.
Cancer Cell ; 13(2): 153-66, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18242515

RESUMO

This study characterized cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) cell lines, tumor specimens, and blood samples. The CD90+ cells, but not the CD90(-) cells, from HCC cell lines displayed tumorigenic capacity. All the tumor specimens and 91.6% of blood samples from liver cancer patients bore the CD45(-)CD90+ population, which could generate tumor nodules in immunodeficient mice. The CD90+CD44+ cells demonstrated a more aggressive phenotype than the CD90+CD44(-) counterpart and formed metastatic lesions in the lung of immunodeficient mice. CD44 blockade prevented the formation of local and metastatic tumor nodules by the CD90+ cells. Differential gene expression profiles were identified in the CD45(-)CD90+ and CD45(-)CD90(-) cells isolated from tissue and blood samples from liver cancer patients and controls.


Assuntos
Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Antígenos Thy-1/metabolismo , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Separação Celular , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
World J Surg ; 40(1): 198-205, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26316115

RESUMO

INTRODUCTION: Laparoscopic left lateral sectionectomy has been proven to be a safe and effective treatment for liver lesions. However, most of the literatures only reported this treatment method on benign lesion or colorectal metastases. The data on long-term outcome of laparoscopic left lateral section resection in patients with HCC and cirrhosis are still limited. The aim of this study is to analyze the survival outcome of laparoscopic left lateral sectionectomy when compared to open approach in patients with HCCs. METHOD: Between January 2004 and September 2014, 967 patients had primary HCC with hepatectomy performed. Twenty-four patients had undergone pure laparoscopic left lateral sectionectomy for hepatocellular carcinoma (HCC). Twenty-nine patients with case-matched tumor characteristics and liver functions but received open left lateral sectionectomy for HCC were included for comparison. RESULTS: Comparing laparoscopic group to open resection group, the median operation time was 190.5 versus 195 min (P = 0.734); the median blood loss was 100 versus 300 ml (P < 0.001). Hospital stay was 5 days in laparoscopic group versus 6 days in the open group (P = 0.057). There was no difference between the two groups in terms of complications (P = 0.495). The median survival in laparoscopic group was >115 months versus >125 months in the open group (P = 0.853). CONCLUSION: Laparoscopic left lateral sectionectomy for HCC is a safe and simple procedure associated with less blood loss. The survival outcome is comparable with conventional open approach. It is becoming a more favorable treatment option even for patients with HCC and cirrhosis.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Feminino , Humanos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
10.
Genomics ; 105(2): 76-82, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25462863

RESUMO

We did whole-transcriptome sequencing and whole-genome sequencing on nine pairs of Hepatocellular carcinoma (HCC) tumors and matched adjacent tissues to identify RNA editing events. We identified mean 26,982 editing sites with mean 89.5% canonical A→G edits in each sample using an improved bioinformatics pipeline. The editing rate was significantly higher in tumors than adjacent normal tissues. Comparing the difference between tumor and normal tissues of each patient, we found 7 non-synonymous tissue specific editing events including 4 tumor-specific edits and 3 normal-specific edits in the coding region, as well as 292 edits varying in editing degree. The significant expression changes of 150 genes associated with RNA editing were found in tumors, with 3 of the 4 most significant genes being cancer related. Our results show that editing might be related to higher gene expression. These findings indicate that RNA editing modification may play an important role in the development of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Genoma , Neoplasias Hepáticas/genética , Edição de RNA , Transcriptoma , Biologia Computacional/métodos , Estudo de Associação Genômica Ampla , Humanos , Análise de Sequência de RNA
11.
HPB (Oxford) ; 18(1): 72-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26776854

RESUMO

BACKGROUND: This study aims to assess if radiofrequency ablation (RFA) has any oncological superiority over transarterial chemoembolization (TACE) on post-hepatectomy recurrence. METHODOLOGY: From 2002 to 2011, 60.15% of 823 patients developed recurrence after hepatectomy for Hepatocellular carcinoma (HCC). 102 patients with recurrence underwent RFA (n = 42) or TACE (n = 60) for tumor size ≤5 cm and number of lesion ≤3 when tumors were not resectable or transplantable. Those with renal impairment, portal vein thrombosis and poor liver reserve were excluded. Primary outcome was overall survival, which was determined using log-rank test and Kaplan Meier plots performed. Categorical data were analyzed using Chi-square test and continuous variable were analyzed using Mann-U Whitney test. RESULTS: Demographics and primary tumor characteristics were similar in both groups (p > 0.05). Overall survival after initial hepatectomy and salvage treatment for recurrence was similar (p > 0.05) in both groups with 5-year OS after salvage treatment for RFA and TACE at 24.1% and 25.7%, respectively. For patients with second recurrence after salvage treatment, an interchangeable treatment strategy of RFA and TACE conferred a better survival outcome than a stand-alone treatment with RFA or TACE (p < 0.05). CONCLUSIONS: RFA and TACE may be equally effective for intrahepatic recurrence after hepatectomy when tumor size is ≤5 cm and ≤3 lesion when re-resection or salvage transplantation is not considered feasible.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Reoperação , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
12.
Lancet Oncol ; 16(13): 1344-54, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26361969

RESUMO

BACKGROUND: There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. METHODS: We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770. FINDINGS: We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6-35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1-38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9-19·5) in the sorafenib group and 8·4 months (2·9-19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780-1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group. INTERPRETATION: Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Hepatectomia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ásia , Austrália , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Método Duplo-Cego , Europa (Continente) , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nova Zelândia , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , América do Norte , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Fatores de Risco , Sorafenibe , América do Sul , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
J Hepatol ; 62(3): 607-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25450711

RESUMO

BACKGROUND & AIMS: The roles of alternatively activated (M2) macrophages on pro-tumour phenotypes have been well documented in many cancers except hepatocellular carcinoma (HCC). Considering their close relationship with chronic tissue injuries as well as enhanced tumour invasiveness and growth, we aimed to investigate the direct effects of M2 macrophages on HCC. METHODS: M2 macrophages in 95 HCC clinical specimens were quantified using immunohistochemistry and quantitative PCR. The pro-tumour functions and the underlying molecular mechanisms of M2 macrophages in HCC were investigated in vivo and in an in vitro co-culture system. RESULTS: In the clinical study, high M2-specific CD163 (hazard ratio=2.693; p=0.043) and scavenger receptor A (hazard ratio=3.563; p=0.044) levels indicated poor prognosis and correlated with increased tumour nodules and venous infiltration in HCC patients. In an orthotopic model, the liver tumour volume was increased 3.26-fold (1.27 cm3±0.36) after M2 macrophage injection compared with the control (0.39 cm3±0.05) (p=0.032). An increased rate of lung metastasis was also found in the treatment group. In vitro, co-cultivation with M2 macrophages elevated the number of HCC cells (MHCC97L) and migration events by 1.3-fold and 3.2-fold, respectively (p<0.05). Strongly induced by MHCC97L, M2 macrophage-derived CCL22 was proven to enhance tumour migration capacities and correlate with venous infiltration in HCC patients. Increased epithelial-mesenchymal transition (EMT) via Snail activation in MHCC97L was found to be promoted by M2 macrophages and CCL22. CONCLUSIONS: M2 macrophages contribute to poor prognosis in HCC and promote tumour invasiveness through CCL22-induced EMT.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Macrófagos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Carcinoma Hepatocelular/secundário , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CCL22/metabolismo , Técnicas de Cocultura , Transição Epitelial-Mesenquimal/imunologia , Feminino , Xenoenxertos , Humanos , Ativação de Macrófagos , Macrófagos/classificação , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Prognóstico , Receptores CCR4/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Depuradores Classe A/metabolismo , Adulto Jovem
14.
Gastroenterology ; 146(7): 1691-700.e3, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24583061

RESUMO

BACKGROUND & AIMS: We aimed to develop a prognostic classification scheme with treatment guidance for Asian patients with hepatocellular carcinoma (HCC). METHODS: We collected data from 3856 patients with HCC predominantly related to hepatitis B treated at Queen Mary Hospital in Hong Kong from January 1995 through December 2008. Data on patient performance status, Child-Pugh grade, tumor status (size, number of nodules, and presence of intrahepatic vascular invasion), and presence of extrahepatic vascular invasion or metastasis were included, and randomly separated into training and test sets for analysis. Cox regression and classification and regression tree analyses were used to account for the relative effects of factors in predicting overall survival times and to classify disparate treatment decision rules, respectively; the staging system and treatment recommendation then were constructed by integration of clinical judgments. The Hong Kong Liver Cancer (HKLC) classification was compared with the Barcelona Clinic Liver Cancer (BCLC) classification in terms of discriminatory ability and effectiveness of treatment recommendation. RESULTS: The HKLC system had significantly better ability than the BCLC system to distinguish between patients with specific overall survival times (area under the receiver operating characteristic curve values, approximately 0.84 vs 0.80; concordance index, 0.74 vs 0.70). More importantly, HKLC identified subsets of BCLC intermediate- and advanced-stage patients for more aggressive treatments than what were recommended by the BCLC system, which improved survival outcomes. Of BCLC-B patients classified as HKLC-II in our system, the survival benefit of radical therapies, compared with transarterial chemoembolization, was substantial (5-year survival probability, 52.1% vs 18.7%; P < .0001). In BCLC-C patients classified as HKLC-II, the survival benefit of radical therapies compared with systemic therapy was even more pronounced (5-year survival probability, 48.6% vs 0.0%; P < .0001). CONCLUSIONS: We collected data from patients with HCC in Hong Kong to create a system to identify patients who are suitable for more aggressive treatment than the currently used BCLC system. The HKLC system should be validated in non-Asian patient populations and in patients with different etiologies of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Técnicas de Apoio para a Decisão , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Estadiamento de Neoplasias/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Povo Asiático , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/mortalidade , Distribuição de Qui-Quadrado , Árvores de Decisões , Feminino , Hong Kong , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Radiology ; 274(1): 133-40, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25162308

RESUMO

PURPOSE: To evaluate alternative schedules for surveillance computed tomography (CT) for patients who underwent hepatectomy for hepatocellular carcinoma ( HCC hepatocellular carcinoma ) and to demonstrate an appropriate schedule on the basis of stratification for risk of recurrence. MATERIALS AND METHODS: CT and pathologic reports for consecutive patients with HCC hepatocellular carcinoma who underwent hepatectomy at one institution were evaluated with institutional review board approval. Univariate and multivariate analyses were performed to identify risk factors for recurrence. Patients were categorized into risk groups on the basis of classification and regression tree analysis. Average recurrence detection rates ( RDR recurrence detection rate s) between consecutive CT scans were calculated for existing and alternative surveillance schedules for each risk group, and the difference in RDR recurrence detection rate was determined by using the Student t test. A P value of less than .05 was considered to indicate a significant difference. Expected delay in diagnosis was also computed for the alternative surveillance schedules for each risk group. RESULTS: Two hundred sixty patients (216 men; mean age, 56.0 years ± 22.5) underwent 2705 CT studies. Independent risk factors for recurrence were microvascular invasion (P = .001), cirrhosis (P = .007), and tumor multiplicity (P = .001). Three risk groups (low, intermediate, and high) were identified. For low- and intermediate-risk groups, average RDR recurrence detection rate was not significantly different in the first 2 years after hepatectomy when the interval was extended from 3 months (3.3% and 4.6%, respectively) to 4 months (4.3% [expected delay, 16 days] and 6.1% [expected delay, 18 days], respectively) or for the subsequent 3 years when the interval was extended from 6 months (1.3% and 3.5%, respectively) to 12 months (2.5% [expected delay, 72 days] and 7.0% [expected delay, 103 days], respectively). This alternative schedule included five (35.7%) fewer CT scans than the 14 in the original schedule, and a reduction in radiation dose and cost during the 5-year follow-up period. CONCLUSION: Posthepatectomy surveillance CT schedules may be tailored and optimized according to stratification by risk of recurrence to reduce the frequency of CT scans without compromising surveillance benefits.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Complicações Pós-Operatórias/patologia , Doses de Radiação , Estudos Retrospectivos , Fatores de Risco
16.
Hepatology ; 60(5): 1697-707, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24996197

RESUMO

UNLABELLED: Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. At termination, median follow-up was approximately 16 months. Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo (median, 26.4 [95% confidence interval {CI}: 19.1 to not reached] vs. 26.1 months [19.0-30.9]; hazard ratio [HR]: 0.90 [95% CI: 0.66-1.23]; log-rank P=0.5280). Brivanib improved TTES/VI (HR, 0.64 [95% CI: 0.45-0.90]), TTP (0.61 [0.48-0.77]), and rate of TACE (0.72 [0.61-0.86]), but not TTDP (0.94 [0.72-1.22]) versus placebo. Most frequent grade 3-4 adverse events included hyponatremia (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). CONCLUSIONS: In this study, brivanib as adjuvant therapy to TACE did not improve OS.


Assuntos
Alanina/análogos & derivados , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica , Neoplasias Hepáticas/tratamento farmacológico , Triazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/efeitos adversos , Alanina/farmacologia , Alanina/uso terapêutico , Quimioterapia Adjuvante , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Falha de Tratamento , Triazinas/efeitos adversos , Triazinas/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem
17.
Invest New Drugs ; 33(2): 496-504, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25666409

RESUMO

This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.1 and modified RECIST criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable for treatment efficacy. Eighteen patients (90%) were hepatitis B carriers. Median age was 61.5 (range 30-75). Overall disease control rate was 13%, with 2 of the 15 patients achieving stable disease for >8 weeks. The median progression-free survival (PFS) was 1.7 (95% CI: 1.67-1.73) months, with median overall survival (OS) of all 20 enrolled patients being 5.2 (95% CI: 3.3-12.0) months. PFS was significantly prolonged in patients with adequate arginine depletion (ADD) >2 months versus those who had ≤2 months of ADD (6.4 versus 1.7 months; p = 0.01). The majority of adverse events (AEs) were grade 1/2 non-hematological toxicities. Transient liver dysfunctions (25%) were the most commonly reported serious AEs and likely due to disease progression. Pharmacokinetic and pharmacodynamic data showed that Peg-rhAgr1 induced rapid and sustained arginine depletion. The overall quality of life of the enrolled patients was well preserved. Peg-rhAgr1 is well tolerated with a good toxicity profile in patients with advanced HCC. A weekly dose of 1600 U/kg is sufficient to induce ADD. Significantly longer PFS times were recorded for patients who had ADD for >2 months.


Assuntos
Antineoplásicos/farmacologia , Arginase/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Polietilenoglicóis/química , Qualidade de Vida , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica , Área Sob a Curva , Arginase/administração & dosagem , Arginase/efeitos adversos , Arginase/farmacocinética , Química Farmacêutica , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Critérios de Avaliação de Resposta em Tumores Sólidos
18.
BMC Cancer ; 15: 264, 2015 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-25885205

RESUMO

BACKGROUND: Granulin-epithelin precursor (GEP), a secretory growth factor, demonstrated overexpression in various human cancers, however, mechanism remain elusive. Primary liver cancer, hepatocellular carcinoma (HCC), ranks the second in cancer-related death globally. GEP controlled growth, invasion, metastasis and chemo-resistance in liver cancer. Noted that GEP gene locates at 17q21 and the region has been frequently reported to be amplified in subset of HCC. The study aims to investigate if copy number gain would associate with GEP overexpression. METHODS: Quantitative Microsatellite Analysis (QuMA) was used to quantify the GEP DNA copy number, and fluorescent in situ hybridization (FISH) was performed to consolidate the amplification status. GEP gene copy number, mRNA expression level and clinico-pathological features were analyzed. RESULTS: GEP DNA copy number determined by QuMA corroborated well with the FISH data, and the gene copy number correlated with the expression levels (n = 60, r = 0.331, P = 0.010). Gain of GEP copy number was observed in 20% (12/60) HCC and associated with hepatitis B virus infection status (P = 0.015). In HCC with increased GEP copy number, tight association between GEP DNA and mRNA levels were observed (n = 12, r = 0.664, P = 0.019). CONCLUSIONS: Gain of the GEP gene copy number was observed in 20% HCC and the frequency comparable to literatures reported on the chromosome region 17q. Increased gene copy number contributed to GEP overexpression in subset of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Dosagem de Genes/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Hepáticas/genética , Idoso , Carcinoma Hepatocelular/patologia , Cromossomos Humanos Par 17/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Neoplasias Hepáticas/patologia , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Progranulinas
19.
World J Surg ; 39(11): 2831-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26239774

RESUMO

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a highly complex operation that demands a thorough understanding of the intrahepatic vascular anatomy and skills in parenchymal transection for the in situ split procedure. In order to minimize adhesion formation after the stage I operation and to avoid iatrogenic tumor rupture during right liver mobilization in large tumors, anterior approach appears to be a logical approach for the in situ split procedure. However, in contrast to the anterior approach adopted for the usual right hepatectomy, the right hepatic artery and biliary pedicle remain intact and undivided during the first operation. To address this issue, we hereby reported our experience of the modified 'anterior approach' for the ALPPS procedure that facilitates a complete in situ parenchymal split. METHODS: Prospectively collected data of 13 patients who underwent the ALPPS procedure by the modified anterior approach for hepatocellular carcinoma from October 2013 to October 2014 were reviewed. RESULTS: The baseline future liver remnant volume (FLR) was 286 ml. The median tumor size was 6.0 cm. After a median of 8 days from stage I operation, the left FLR hypertrophied by 52.7 % in volume to 482 ml. All patients proceeded to second stage hepatectomy (extended right hepatectomy, n = 5; right hepatectomy, n = 6; right trisectionectomy, n = 2) without significant adhesion encountered. The overall morbidity and mortality rates were 7.7 % (n = 1) and 7.7 % (n = 1), respectively. CONCLUSION: The modified anterior approach is safe and feasible for complete in situ split in the ALPPS procedure.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Hipertrofia/patologia , Ligadura , Neoplasias Hepáticas/patologia , Regeneração Hepática , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Veia Porta/cirurgia , Estudos Retrospectivos , Carga Tumoral , Procedimentos Cirúrgicos Vasculares
20.
World J Surg ; 39(11): 2764-70, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26154577

RESUMO

BACKGROUND: Right hepatectomy (RH) instead of right posterior sectionectomy (RPS) is commonly performed for hepatocellular carcinoma (HCC) in cirrhotic livers located lateral to the right hepatic vein in order to ensure adequate resection margin. This potentially increased the risk of postoperative liver failure. This study aims to compare survival outcomes and surgical morbidities between RH and RPS. METHODS: All patients between 2003 and 2013 with resection for solitary HCC in cirrhotic livers at segment 6/7 were reviewed. Baseline demographics, liver function, perioperative outcomes, and overall (OS) and disease-free survival (DFS) were compared between RH and RPS. RESULTS: Eighty-one patients were included in this study. Thirty-two patients had RH and forty-nine with RPS were selected as controls. Majority of the HCC patients (91.4 %) suffered from chronic hepatitis B. There was no significant difference in age, gender and Child-Pugh grade between the two groups. The median tumour size of RH group was 6 vs. 4 cm in the RPS group (p < 0.0001). Both groups had no statistical difference in resection margin and their associated morbidities. The 5-year OS for RH and RPS was 76 and 83.8 %, respectively (p = 0.766), whereas their corresponding DFS was 52.6 and 52.2 % (p = 0.859). Despite the discrepancy of tumour size among the two groups, there was no statistical difference in subgroup analysis based on their corresponding stage of disease. CONCLUSION: RPS can achieve similar OS and DFS as RH for HCC, and should be considered as the treatment of choice in order to optimise the postoperative remnant parenchymal liver functions.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Veias Hepáticas/cirurgia , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/complicações , Falência Hepática , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Taxa de Sobrevida , Carga Tumoral
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