Controversies and evidence of hepatic resection for hepatocellular carcinoma.
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ABSTRACT:
SUBMITTER: Zhong JH
PROVIDER: S-EPMC5067978 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCancer-related inflammation has been correlated with cancer prognosis. This study evaluated inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), programmed death ligand (PD-L) 1 expression, and tumour microenvironment in relation to prognosis and clinicopathological features of patients with hepatocellular carcinoma (HCC) undergoing curative hepatic resection.MethodsPatients who had liver resection for HCC in 2000-2011 were analysed. Univariable and multivariable analyses were conducted for overall (OS) and recurrence-free (RFS) survival. Immunohistochemical analyses of PD-L1, CD8 and CD68 expression were performed. HCC cell lines were evaluated for PD-L1 expression. A subgroup analysis was conducted to determine patient features, survival and the tumour microenvironment. Results were validated in a cohort of patients with HCC treated surgically in 2012-2016.ResultsSome 281 patients who underwent hepatic resection for HCC were included. Multivariable analysis showed that low LMR was an independent prognostic factor of OS (hazard ratio (HR) 1·59, 95 per cent c.i. 1·00 to 2·41; P = 0·045) and RFS (HR 1·47, 1·05 to 2·04; P = 0·022) after resection. Low preoperative LMR values were correlated with higher α-fetoprotein values (P < 0·001), larger tumour size (P < 0·001), and high rates of poor differentiation (P = 0·035) and liver cirrhosis (P = 0·008). LMR was significantly lower in PD-L1-positive patients than in those with PD-L1 negativity (P < 0·001). Results were confirmed in the validation cohort. PD-L1 expression was upregulated in HCC cell lines treated with interferon-γ and co-cultured with THP-1 monocyte cells.ConclusionLMR is an independent predictor of survival after hepatic resection in patients with HCC. Modulation of the immune checkpoint pathway in the tumour microenvironment is associated with a low LMR.
| S-EPMC6677099 | biostudies-literature
Project description:The management of hepatocellular carcinoma (HCC) has evolved considerably over the last decade. Surveillance of cirrhotic patients and refinements to imaging techniques have enabled a relevant proportion of patients to be diagnosed at an early stage, when effective therapies are feasible. Resection, transplantation and ablation are all options in patients with early stage HCC. Thus, there is some controversy regarding which is the best treatment approach in challenging scenarios. There have also been major developments in locoregional therapies, particularly in intra-arterial approaches. Finally, the systemic treatment for HCC has changed dramatically following the demonstration of a survival benefit with sorafenib; there are currently several first-line (sorafenib and lenvatinib) and second-line (regorafenib, cabozantinib and ramucirumab) treatments that have shown a survival benefit. Expectations for immune checkpoint inhibitors are high, with the results of the ongoing phase III trials eagerly awaited. In this review we discuss some of the controversies in the management of HCC, focussing in particular on systemic therapy.
| S-EPMC7001551 | biostudies-literature
Project description:Purpose:Although there are several prospective clinical studies comparing radiofrequency ablation (RFA) and hepatic resection (HR) for the treatment of hepatocellular carcinoma, there are few trials that have been performed in strictly homogeneous patients. Methods:Patients who were newly diagnosed with a solitary hepatocellular carcinoma were randomized to the HR or RFA group. Inclusion criteria were as follows: age ? 20 years but ? 70 years, Child-Pugh class A, maximal diameter of the tumor ? 2 cm but ? 4 cm, no previous treatment history, and platelet count > 80,000/mm3. Results:Although the study was early terminated, 29 and 34 patients were enrolled in the HR and RFA groups, respectively, and prospectively followed on an intention-to-treat basis. The 5-year overall survival rates were 83.4% and 86.2% in the HR and RFA groups, respectively, which were not significantly different (P = 0.812 by log-rank, P = 0.990 by Breslow). The 3- and 5-year disease-free survival rates in the HR group were significantly superior to those in the RFA group (66.7%, 44.4% vs. 44.1%, 31.2%, P = 0.071 by log-rank, P = 0.023 by Breslow). Intrahepatic local recurrence tended to develop more frequently in the RFA group (P = 0.042), while the frequency of intrahepatic distant and extrahepatic recurrence was similar bet ween the 2 groups. There were no significant differences in the frequency and severity of complications between the 2 groups. Conclusion:HR was significantly superior to RFA in terms of disease-free survival; however, the overall survival was excellent in both groups.
| S-EPMC5801331 | biostudies-literature
Project description:BackgroundThe clinical benefits of treatment with radiofrequency ablation (RFA) and repeat hepatic resection (RHR) for recurrent hepatocellular carcinoma (RHCC) remain controversial. This meta-analysis aims to evaluate the outcomes and major complications of RFA versus RHR in patients with early-stage RHCC.MethodsPubMed, Embase, Web of Science and the Cochrane Library were systematically searched for comparative studies on the evaluation of RHR versus RFA for RHCC. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and major complications. Meta-analysis was performed using a random-effects model or fixed-effects model, and heterogeneity was tested by the Cochran Q statistic.ResultsTen studies with 1612 patients (RHR = 654, RFA = 958) were included in the meta-analysis. The meta-analysis showed that RHR had superior OS (HR 0.77, 95% CI =0.65-0.92, P = 0.004) and PFS (HR 0.81, 95% CI =0.67-0.98, P = 0.027) compared to RFA, whereas major complications may be less frequent in the RFA group (OR 0.15, 95% CI = 0.06-0.39, P < 0.001). In the subgroup analysis of patients with single RHCC ≤3 cm, OS (HR 1.03, 95% CI =0.69-1.52, P = 0.897) and PFS (HR 0.99, 95% CI = 0.71-1.37, P = 0.929) showed no significant differences in the comparison of RHR and RFA. In single RHCC> 3 cm and ≤ 5 cm, RFA showed an increased mortality in terms of OS (HR 0.57, 95% CI = 0.37-0.89, P = 0.014).ConclusionRHR offers a longer OS and PFS than RFA for patients with RHCC, but no statistically significant difference was observed for single RHCC ≤3 cm. The advantages of fewer major complications may render RFA an alternative treatment option for selected patients.
| S-EPMC7693504 | biostudies-literature
Project description:Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS), predicts cancer-specific survival in various cancer types. The aim of this study was to evaluate the significance of the GPS in the therapeutic outcome of the patient following surgical resection for hepatocellular carcinoma. In total, 144 patients underwent surgical resection for hepatocellular carcinoma. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10). Retrospectively, the relationship between patient characteristics including GPS, disease-free as well as overall survival were investigated. In disease-free survival, GPS 2 (P=0.019), with a tumor number ≥3 (P=0.004), and positive portal or venous invasion (P=0.034) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, GPS 1 (P=0.042), GPS 2 (P<0.001) and positive portal or venous invasion (P<0.001) were independent predictors of poor patient outcome according to multivariate analysis. To conclude, the GPS in patients with hepatocellular carcinoma is an independent prognostic predictor after hepatic resection.
| S-EPMC5494858 | biostudies-other
Project description:Purpose: We have developed a systemic hepatic-damage index (SHI) based on serum total cholesterol (TC) and high density lipoprotein levels (HDL) and determined its prognostic significance in hepatocellular carcinoma (HCC) patients undergoing resection. Experimental Design: The SHI was analyzed in the training cohort of 188 HCC patients and in the validation cohort of 177 HCC patients. The systemic immune-inflammation index (SII) scores in the validation cohorts were also measured. Area under the receiver operating characteristic curve (AUC) was used to explore the prediction accuracy in HCC patients. Results: An optimal cutoff point for the SHI of 2.84 stratified the HCC patients into high SHI (>2.84) and low SHI (≤2.84) groups in the training cohort. Univariate and multivariate analyses revealed the SHI was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative α-fetoprotein and Barcelona Clinic Liver Cancer stage 0+A. The AUCs of the SHI for survival and recurrence were higher than other conventional clinical indices. Low SHI significantly correlated with vascular invasion. The SII scores were significantly higher in patients with low SHI compared with those with high SHI. HCC patients in SHI ≤ 2.84 group had shorter recurrence time and lower survival rate than HCC patients in SHI > 2.84 group. Conclusions: The SHI was a potential biomarker for assessing HCC prognosis, and improving SHI level in HCC patients may be a promising therapeutic strategy decision. The poor outcome in HCC patients with low SHI scores might increase SII scores, increasing the possibility of recurrence and metastasis.
| S-EPMC5513961 | biostudies-literature
Project description:Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes-freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)-was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p < 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification.
| S-EPMC7281651 | biostudies-literature
Project description:The present study aimed to investigate the long-term and perioperative outcomes of precise hepatic pedicle dissection in anatomical resection (precise AR) vs non-anatomical resection (NAR) for hepatocellular carcinoma (HCC) patients.Data from a total of 270 consecutive HCC patients who underwent curative hepatectomy were retrospectively collected. Propensity score matching (PSM) analysis was performed. The long-term outcomes of precise AR and NAR were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.The 1-, 3-, and 5-year overall survival (OS) rates were 90.3%, 76.2%, and 65.7% in the PS-precise AR group, respectively (n = 103); and 88.3%, 70.5%, and 52.0% in the PS-NAR group, respectively (n = 103) (P = .043). The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 83.4%, 63.2%, and 46.0% in the PS-precise AR group, respectively; and 75.7%, 47.4%, and 28.3% in the PS-NAR group, respectively (P = .002). Multivariate analysis showed that ICG-R15, BCLC staging, and microvascular invasion (MVI) were independent risk factors for OS; while tumor size, types of resection, surgical margin, and MVI were independent risk factors for RFS. Subgroup analysis indicated that the RFS rate was significantly better in the PS-precise AR group than in the PS-NAR group for patients with MVI and tumor size ≤5 cm.After PSM, precise hepatic pedicle dissection in AR significantly improved the recurrence-free survival rate of solitary HCC patients compared with NAR, especially in those with MVI and tumor size ≤5 cm.
| S-EPMC7478661 | biostudies-literature
Project description:BackgroundThe selection criteria for hepatic resection (HR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) are still controversial. We used real-world data to evaluate the overall survival (OS) in treatment with HR or transarterial chemoembolization (TACE).MethodsIn total, 942 patients with IM-HCC were categorized into the HR group and the TACE group. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analysis. Curve smoothing was performed through the generalized additive model. The interaction test was performed to evaluate the impact of HR on OS concerning risk factors. Also, we used multiple imputation to deal with missing data.ResultsIn total, 23.0% (n = 225) of patients received HR. At a median OS of 23.7 months, HR was associated with improved OS in the multivariate analysis [hazard ratio (HzR) = 0.45, 95%CI = 0.35-0.58; after PSM: HzR = 0.56, 95%CI = 0.41-0.77]. Landmark analyses limited to long-term survivors of ≥6 months, ≥1 year, and ≥2 years demonstrated better OS with HR in all subsets (all p < 0.05). After PSM analysis, however, HR increased the risk of death by 20% (HzR = 1.20, 95%CI = 0.67-2.15) in the subgroup of patients with lactate dehydrogenase (LDH) ≤192 U/L (p for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and HR with respect to the 1-, 3-, and 5-year observed survival rates (all p < 0.05).ConclusionHR was superior to TACE for intermediate-stage HCC in patients with LDH levels >192 U/L. Moreover, TACE might be suitable for patients with LDH levels ≤192 U/L.
| S-EPMC8579001 | biostudies-literature
Project description:BACKGROUND: Lysosomal protein transmembrane 4 beta (LAPTM4B) is a gene related to hepatocellular carcinoma that has two alleles designated LAPTM4B*1 and LAPTM4B*2. This study aimed to investigate the correlation of LAPTM4B genotype with prognosis and clinicopathologic features in patients who have undergone resection for hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: The LAPTM4B genotype was analyzed by PCR in 68 patients who had undergone curative hepatic resection for hepatocellular carcinoma. The correlation of LAPTM4B genotype with clinicopathologic parameters was assessed with the Chi-squared test. Differences in patient survival were determined by the Kaplan-Meier method. Multivariate analysis of prognostic factors was carried out with Cox regression analysis. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both P<0.001). Multivariate analysis showed that LAPTM4B genotype is an independent prognostic factor for OS and DFS (both P<0.001). CONCLUSIONS/SIGNIFICANCE: Allele *2 of LAPTM4B is a risk factor associated with poor prognosis in patients with resected HCC. LAPTM4B status may be useful preoperatively as an adjunct in evaluation of the operability of HCC.
| S-EPMC3318008 | biostudies-literature