Treatment Of Hepatocellular Carcinoma Patients Research Articles

Phosphorylation of mTOR Ser2481 is a key target limiting the efficacy of rapalogs for treating hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although recent studies facilitate the identification of crucial genes and relevant regulatory pathways, therapeutic approaches against advanced HCC are insufficiently effective. Therefore, we aimed here to develop potent therapeutics to provide a reliable biomarker for the therapeutic efficacy in patients with HCC. To this end, we first compared the cytotoxic effects of various anti-cancer drugs between well differentiated (HAK-1A) and poorly differentiated (HAK-1B) cell lines established from a single HCC tumor. Of various drug screened, HAK-1B cells were more sensitive by a factor of 2,000 to the mTORC1 inhibitors (rapalogs), rapamycin and everolimus, than HAK-1A cells. Although rapalogs inhibited phosphorylation of mTOR Ser2448 in HAK-1A and HAK-1B cells, phosphorylation of mTOR Ser2481 was specifically inhibited only in HAK-1B cells. Silencing of Raptor induced apoptosis and inhibited the growth of only HAK-1B cells. Further, three other cell lines established independently from the tumors of three patients with HCC were also approximately 2,000-fold times more sensitive to rapamycin, which correlated closely with the inhibition of mTOR Ser2481 phosphorylation by rapamycin. Treatment with everolimus markedly inhibited the growth of tumors induced by poorly differentiated HAK-1B and KYN-2 cells and phosphorylation of mTOR Ser2481 in vivo. To our knowledge, this is the first study showing that the phosphorylation of mTOR Ser2481 is selectively inhibited by rapalogs in mTORC1-addicted HCC cells and may be a potential reliable biomarker for the therapeutic efficacy of rapalogs for treating HCC patients.

Investigation of potential molecular biomarkers and small molecule drugs for hepatocellular carcinoma transformed from cirrhosis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China and the third leading cause of cancer-associated morality. The aim of the present study was to investigate and analyze differentially-expressed genes (DEGs) between cirrhosis and HCC, in order to screen the key genes involved in the transformation from cirrhosis to HCC and provide novel targets for the diagnosis and treatment of HCC in patients with cirrhosis. The gene expression profile, GSE17548, was obtained from Gene Expression Omnibus database and the DEGs were identified by LIMMA package in R language. Kyoto Encyclopedia of Genes and Genomes and gene ontology biology process analysis were performed for the DEGs. Differential co-expression network (DEN) analysis was conducted and the network was visualized using Cytoscape. Small molecule drugs were also screened from the Comparative Toxicogenomics Database for higher degree DEGs. A total of 95 DEGs were obtained, including 46 upregulated and 49 downregulated genes. The upregulated DEGs were primarily involved in biological processes and pathways associated with the cell cycle, while the downregulated DEGs were primarily involved in immune-associated biological processes. A total of 22 key DEGs were identified by DEN analysis, which distinguished HCC from cirrhosis samples. Furthermore, estradiol, benzo(a)pyrene, acetaminophen, copper sulfate and bisphenol A were identified as the five most associated chemicals to these 22 DEGs. In conclusion, the hub genes and chemicals identified by the present study may provide a theoretical basis for additional research on diagnosis and treatment of HCC transformed from cirrhosis.

Statins improve outcomes of non-surgical curative treatments in hepatocellular carcinoma patients: cohort study from Taiwan cancer registry.

e15627Background: Statins are associated with a reduced risk of hepatocellular carcinoma (HCC) and have the potential to be an adjuvant agent for HCC. In this study, we examined whether statin use ...

Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy.

Lymphocytes are an integral part of lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI). Both LMR and PNI which reflect body's inflammatory and nutritional status can be obtained from routine blood and biochemical test conveniently. Little evidence concerning the prognostic value of LMR and PNI in hepatocellular carcinoma (HCC) patients has been published. This study aimed to investigate the prognostic value of LMR and PNI in hepatitis B virals (HBV)-associated HCC patients who underwent curative hepatectomy. Between January 2008 and June 2013, 450 surgically treated HCC patients were retrospectively analyzed. Clinicopathological parameters, LMR and PNI were collected and compared. The multivariate analysis was performed to indentify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) rates were also compared. Tumor size, vascular invasion, alpha fetoprotein level, LMR and PNI were independent prognostic factors for OS. Tumor number, tumor size, vascular invasion, LMR and PNI were independent prognostic factors for RFS. Either a high LMR or PNI could predict favorable OS and RFS in surgically treated HCC patients and vice versa. Both LMR and PNI were significant independent predictors that can predict survival outcomes in HBV-associated HCC patients who received curative hepatectomy. J. Surg. Oncol. 2016;114:202-210. © 2016 Wiley Periodicals, Inc.

Effects of in-hospital exercise on liver function, physical ability, and muscle mass during treatment of hepatoma in patients with chronic liver disease.

Sarcopenia and physical disability assessed by a 6-min walking test (6MWT) are associated with poor prognosis of patients with chronic liver disease (CLD). However, CLD patients with hepatocellular carcinoma (HCC) mostly rest in bed during hospitalization. We aimed to investigate the effects of therapeutic exercise on liver function, 6MWT, and skeletal muscle mass during HCC treatment in patients with CLD. We enrolled 54 CLD patients with HCC (median age, 76years). During hospitalization, patients performed a combination of stretching, strength training, balance practice, and endurance training (2.5-4 metabolic equivalents/20min/day). Primary outcomes were changes from admission to discharge in Child-Pugh class, 6MWT, and skeletal muscle mass. Furthermore, factors associated with skeletal muscle atrophy were analyzed by a decision-tree analysis. Exercise did not worsen the Child-Pugh class. On discharge, the 6MWT ambulation distance was maintained, and heart rate variability during the 6MWT was significantly improved compared to that on admission (area under the curve 50.3 vs. 39.0 arbitrary units; P = 0.0027). Although skeletal muscle mass was significantly reduced (20.6kg vs. 20.0kg, P = 0.0301), branched-chain amino acid (BCAA) treatment was identified as the most distinguishable factor for minimizing muscle mass atrophy (-1.1kg vs. -0.5kg/hospitalization). Therapeutic exercise improved physical ability without worsening liver function during hospitalization for HCC treatment in CLD patients. Although exercise did not completely prevent skeletal muscle atrophy, BCAA treatment minimized the skeletal muscle atrophy. Thus, exercise with BCAA treatment may be important for the management of CLD patients with HCC.

Sorafenib-resistant hepatocellular carcinoma stratified by phosphorylated ERK activates PD-1 immune checkpoint

Sorafenib is a multikinase inhibitor approved as the first line treatment for late stage hepatocellular carcinoma (HCC). Due to its significant variation in clinical benefits among patients, defining prognostic biomarkers for sorafenib sensitivity in HCC would allow targeted treatment. Phosphorylated extracellular signaling-regulated kinase (pERK) was proposed to predict the response to sorafenib in HCC, but clinical supports are mixed or even contradictory. Here we found that pERK expression levels are variable in different nodules from individual patient liver. Xenografts derived from resected tumors are resistant to sorafenib inhibition when expressing low levels of pERK. This correlation of low pERK levels and sorafenib resistance is corroborated by histological characterization of chemical-induced and genetic mouse models for pERK-positive and pERK-negative HCC respectively, as well as computed tomography (CT) imaging of patient tumors with validated pERK expression. Mouse and human HCC samples expressing low pERK show strong inflammatory infiltrating cells and significant enrichment of intratumoral CD8+ cytotoxic T lymphocytes that express programmed death receptor-1 (PD-1). These pERK−PD-1+ patients have poorer overall and disease-free survival than pERK+PD-1− patients. In conclusion, our data suggest that anti-PD-1 immunotherapy might complement sorafenib in treating HCC patients by targeting sorafenib-resistant cancer cells, and the dual pERK and PD-1 biomarkers would help HCC patient selection to achieve optimal clinical benefits.

GALNT14 genotype effectively predicts the therapeutic response in unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization.

Transcatheter arterial chemoembolization is currently the standard treatment in hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer stage B. Genomic variants of GALNT14 were recently identified as effective predictors for chemotherapy responses in Barcelona Clinic Liver Cancer stage C patients. We investigated the prognosis predictive value of GALNT14 genotypes in 327 hepatocelluar carcinoma patients treated by transcatheter arterial chemoembolization. Cox proportional hazards model analysis showed that the genotype 'TT' was associated with shorter time-to-response (multivariate p < 0.001), time-to-complete-response (p = 0.004) and longer time-to-tumor progression (p < 0.001), compared with the genotype 'non-TT'. In patients with albumin <3.5 g/dl, genotype 'TT' was associated with longer overall survival (p = 0.027). Finally, genotype 'TT' correlated with higher cancer-to-noncancer ratios of GALNT14 protein levels, lower cancer-to-noncancer ratios of antiapoptotic cFLIP-S, and a clustered glycosylation pattern in the extracellular domain of death receptor 5. GALNT14 genotypes were significantly associated with clinical outcomes of transcatheter arterial chemoembolization. The differential status of extrinsic apoptotic signaling between cancerous and non-cancerous tissues might underlie the clinical association.

Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.

Microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis

Purpose: Radiofrequency ablation (RFA) and microwave ablation (MWA) are the two main percutaneous techniques for the treatment of unresectable hepatocellular carcinoma (HCC). However, to date, studies comparing the two therapies have provided discordant results. The aim of this meta-analysis is to evaluate the efficacy and safety of the two treatments for HCC patients. Materials and methods: A computerised bibliographic search was performed on PubMed/MEDLINE, Embase, Google Scholar and Cochrane library databases. The rates of complete response (CR), local recurrence (LRR), 3-year survival (SR) and major complications were compared between the two treatment groups by using the Mantel-Haenszel test in cases of low heterogeneity or the DerSimonian and Laird test in cases of high heterogeneity. Sources of heterogeneity were investigated using subgroup analyses. In order to confirm our finding, sensitivity analysis was performed restricting the analysis to high-quality studies. Results: One randomised controlled trial (RCT) and six retrospective studies with 774 patients were included in the meta-analysis. A non-significant trend of higher CR rates in the patients treated with MWA was found (odds ratio (OR) = 1.12, 95% confidence interval (CI) 0.67–1.88, p = 0.67]. Overall LRR was similar between the two treatment groups (OR 1.01, 95% CI 0.53–1.87, p = 0.98) but MWA outperformed RFA in cases of larger nodules (OR 0.46, 95% CI 0.24–0.89, p = 0.02). 3-year SR was higher after RFA without statistically significant difference (OR 0.95, 95% CI 0.58–1.57, p = 0.85). Major complications were more frequent, although not significantly, in MWA patients (OR 1.63, 95% CI 0.88–3.03, p = 0.12). Conclusions: Our results indicate a similar efficacy between the two percutaneous techniques with an apparent superiority of MWA in larger neoplasms.

Portal Vein Stenting Combined with Iodine-125 Seeds Endovascular Implantation Followed by Transcatheter Arterial Chemoembolization for Treatment of Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus.

Aim was to assess the therapeutic value of portal vein stenting (PVS) combined with iodine-125 seed (125I seed) strand endovascular implantation followed by transcatheter arterial chemoembolization (TACE) for treating patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). This was a retrospective study of 34 patients aged 29–81 years, diagnosed HCC with PVTT, and treated with PVS combined with 125I seed strand endovascular implantation followed by TACE between January 2012 and August 2014. Survival, stent patency, technical success rate, complications related to the procedure, and adverse events were recorded. The technical success rate was 100%. No serious procedure-related adverse event was recorded. The median survival was 147 days. The cumulative survival rates and stent patency rates at 90, 180, and 360 days were 94.1%, 61.8%, and 32.4% and 97.1% (33/34), 76.9% (24/34), and 29.4% (10/34), respectively. PVS combined with 125I seed strand endovascular implantation followed by TACE is feasible for patients with HCC and PVTT. It resulted in appropriate survival and stent patency, with no procedure-related adverse effects.

Impact of clinically significant portal hypertension on surgical outcomes for hepatocellular carcinoma in patients with compensated liver cirrhosis: a propensity score matching analysis.

Backgrounds/AimsThe roles of portal hypertension (PHT) on the postoperative course after hepatectomy are still debated. The aim of this study was to evaluate surgical outcomes of hepatectomy in patients with PHT.MethodsData from 152 cirrhotic patients who underwent hepatectomy for hepatocellular carcinoma (HCC) were collected retrospectively. Patients were divided into two groups according to the preoperative presence of PHT as follows: 44 patients with PHT and 108 without PHT. Propensity score matching (PSM) analysis was used to overcome selection biases.ResultsThere were no significant differences in morbidity (56.8% vs. 51.9%, p=0.578) and 90-days mortality (4.5% vs. 4.6%, p=0.982) between the two groups. Post-hepatectomy liver failure (PHLF) was not significantly different between the two groups (43.2% vs. 35.2%, p=0.356). Patients without PHT had a better 5-year disease-free survival than those with PHT, although the difference did not reach statistical significance (30.9% vs. 17.2%, p=0.081). Five-year overall survivals were not significantly different between the two groups (46.6% vs. 54.9%, p=0.724). Repeat analyses after PSM showed similar rates of morbidity (p=0.819), mortality (p=0.305), PHLF (p=0.648), disease-free survival (p=0.241), and overall survival (p=0.619). The presence of PHT was not associated with either short-term or long-term poor surgical outcomes.ConclusionsChild-Pugh A and B patients with PHT have surgical outcomes similar to those without PHT. Hepatectomy can be safely performed and can also be considered as a potentially curative treatment in HCC patients with PHT.

Hepatocellular carcinoma: Where are we?

Hepatocellular carcinoma (HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type II diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called "up to seven criteria" to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients.

Risk prediction models for hepatocellular carcinoma in different populations.

Hepatocellular carcinoma (HCC) is a malignant disease with limited therapeutic options due to its aggressive progression. It places heavy burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well.

Treatment of hepatocellular carcinoma with portal venous tumor thrombosis: A comprehensive review.

The natural history of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal (approximately 2-4 mo), and PVTT is reportedly found in 10%-40% of HCC patients at diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) Staging System (which is the most widely adopted HCC management guideline), sorafenib is the standard of care for advanced HCC (i.e., BCLC stage C) and the presence of PVTT is included in this category. However, sorafenib treatment only marginally prolongs patient survival and, notably, its therapeutic efficacy is reduced in patients with PVTT. In this context, there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options. To date, many studies on transarterial chemoembolization, 3-dimensional conformal radiotherapy, hepatic arterial chemotherapy, and transarterial radioembolization report better overall survival than sorafenib therapy alone, but their outcomes need to be verified in future prospective, randomized controlled studies in order to be incorporated into current treatment guidelines. Additionally, combination strategies have been applied to treat HCC patients with PVTT, with the hope that the possible synergistic actions among different treatment modalities would provide promising results. This narrative review describes the current status of the management options for HCC with PVTT, with a focus on overall survival.

Liver resection for hepatocellular carcinoma in patients with portal hypertension: the role of laparoscopy.

Liver resection (LR) for hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is a major issue since patients are at risk of serious intraoperative and postoperative complications. The current EASL/AASLD guidelines recommend LR only in case of patients with stage A HCC with well-preserved liver function and consider the presence of portal hypertension (PHT) as a contraindication to surgery. Nevertheless, the literature on this topic is conflicting. Recently several studies reported that favorable outcomes can be achieved with a careful patients' selection in high volume centers. Laparoscopic LR, when performed by well-trained surgeons and with appropriate indications, proved to be a valid option for the surgical treatment of HCC on cirrhosis offering similar oncologic outcomes but a reduction in surgical related morbidities. Laparoscopic LR thanks to a reduction in the incidence of post-operative liver failure and ascites development in comparison to standard open LR could, in selected cases challenge alternative treatments in the treatment of HCC patients with preserved liver function and clinical signs of mild PHT.

Impact of age on the prognosis after liver transplantation for patients with hepatocellular carcinoma: a single-center experience.

BackgroundLiver transplantation (LT) offers the most effective treatment for hepatocellular carcinoma patients. Various preoperative variables are correlated with survival after LT, but the prognostic role of aging on LT remains controversial.MethodsBetween January 2001 and December 2011, 290 consecutive transplants for patients with hepatocellular carcinoma performed in Shanghai First People’s Hospital (People’s Republic of China) were analyzed retrospectively. We compared patient characteristics and survival curves between a younger group (less than 49 years, n=135) and an aged group (50 years or older, n=155). We then performed Cox multivariate regression analysis of the risk factors for survival in aged and younger patients.ResultsYounger age was associated with higher alpha-fetoprotein (P=0.014), larger tumor size (P=0.038), poorer differentiation (P=0.025), portal lymph node metastasis (P=0.001), and higher recurrence rate (P=0.038). Aged patients had significantly longer recurrence-free survival and overall survival (P=0.020 and P=0.014, respectively); however, there were no significant differences between the younger and aged patients who met the Milan criteria (P>0.05). The 1-, 3-, and 5-year recurrence-free survival rates were 59.7%, 44.5%, and 37.3%, respectively, in the younger group, and 67.9%, 55.3%, and 53.8%, respectively, in the aged group. The 1-, 3-, and 5-year overall survival rates were 68.4%, 45.5%, and 38.9%, respectively, in the younger group, and 76.1%, 59.7%, and 53.9%, respectively, in the aged group. Alpha-fetoprotein ≥400 ng/mL, microvascular invasion, and tumor size >5 cm were independent risk factors for prognosis in both groups.ConclusionYounger patients in our center tended to present with more aggressive tumors and have a higher risk of recurrence. Our single-center experience suggests that younger patients should be assessed more rigorously before LT, while aged patients should be actively considered for LT after appropriate selection.

Multispecialist Care and Mortality in Hepatocellular Carcinoma

Multidisciplinary physician care has increased for many cancers yet little evidence exists for hepatocellular carcinoma (HCC). The purpose of this study was to explore the association between multispecialist care and mortality in HCC. Treated patients with an HCC primary diagnosis from 2000 to 2007 were studied using Surveillance, Epidemiology, and End Results-Medicare data. A surrogate variable for multidisciplinary care was defined-multispecialist care-as the number of disciplines among surgeons, radiology oncologist, intervention radiologist, hematologist/medical oncologist, gastroenterologist, and generalist in the pretreatment period. Multivariate survival analysis was conducted and adjusted for selection and survival bias. Of 3588 treated HCC patients, 1434 (40%) saw 1, 1343 (37%) saw 2, and 811 (23%) saw 3 or more specialists. Patients with multispecialist care received treatment that differed from patients who saw a single specialist. In propensity score-adjusted survival analysis, patients who saw 3 or more specialist types were associated with 10% (P=0.04) reduced mortality, compared with those who saw 1 specialist. When stratified by treatment received, patients on chemotherapy who saw 3 or more specialist types were associated with 28% (P=0.002) reduced mortality, compared with those who saw 1 specialist. Multispecialist care for treated HCC patients was associated with reduced mortality, particularly among chemotherapy recipients. While adjusting for selection and survival bias, our study is limited in capturing a causal relationship between coordinated multidisciplinary care and mortality. Our findings may provide support for the development of coordinated care delivery models but should be confirmed through more rigorous examination in future studies.

The Eltrombopag antitumor effect on hepatocellular carcinoma.

Currently, sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC), but it cannot be used in patients with liver cirrhosis (LC) or thrombocytopenia. In these cases, sorafenib is likely effective if given in combination with treatments that increase the number of platelets, such as thrombopoietin (TPO) receptor agonists. Increasing the platelet count via TPO treatment resulted in reduction of LC. Eltrombopag (EP), a TPO receptor agonist, has been reported to have antitumor effects against certain cancers, despite their lack of TPO receptor expression. We hypothesized that EP may possess antitumor activity against HCC in addition to its ability to suppress hepatic fibrosis by increasing the platelet count. In the present study, the antitumor activity of EP was examined by assessing the inhibition of cell proliferation and then ascertaining the ability of iron supplementation to reverse these effects in HepG2, Hep3B and Huh7 cells. In addition, a cell cycle assay was performed using flow cytometry, and signal transduction was evaluated by analyzing cell cycle-related protein expression. The results of EP were compared with those of the most common iron chelator, deferoxamine (DFO). The combined effect of EP and sorafenib was also assessed. The results revealed that EP exerts antitumor activity in HCC that is mediated by the modulation of intracellular iron content. EP suppressed the expression of the cell cycle-related protein cyclin D1 and elicited cell cycle arrest in the G0/G1 phase. The activity of EP was comparable to that of DFO in HCC, and EP did not compete with sorafenib at low concentrations. In conclusion, our findings suggest that EP is a good candidate chemotherapeutic agent for the treatment of HCC in patients with LC and thrombocytopenia.

Long-term outcome of laparoscopic ablation therapies for unresectable hepatocellular carcinoma: a single European center experience of 426 patients.

Radiofrequency ablation (RFA) is widely used as a first-line option in patients with hepatocellular carcinoma (HCC). However, since percutaneous approach of RFA may be, in some cases, unfeasible by the tumor size and its location, laparoscopic ablation therapies (LATs) were used as an alternative. Objective of the present study was to assess the efficacy of laparoscopic ultrasound examination in addition to LATs in the treatment of HCC in patients not eligible for percutaneous RFA or surgical resection. Four hundred and twenty-six patients who underwent LATs were analyzed. Laparoscopic approach was offered to patients fulfilling at least one of the following criteria: (a) patients with a single nodule or up to three nodules smaller than 3cm not suitable for liver transplantation or not eligible for HR because of severe portal hypertension, impaired liver function, or coexistent comorbidities; (b) patients not suitable for percutaneous RFA because of inconvenient tumor location; and (c) short-term recurrence of HCC (<3months). Technical success was achieved in one session in 396 patients (93%). One-month mortality and morbidity rates were 0.23% (1 patient) and 25% (106 patients), respectively. During a median follow-up of 37.2months (range 2-193) in the remaining 425 patients, 276 (65%) developed intra-hepatic recurrence: It appeared as a local tumor progression in 65 cases (15%). Patients median survival was 39months (95% CI 34.8-47.2), while overall survivals at 1, 3, and 5years were 88, 55, and 34%, respectively. In the treatment of HCC, LATs proved to be a safe and effective technique, as they permit to treat with low-morbidity-rate lesions not manageable by percutaneous approach. Moreover, they allow achieving a more accurate staging of the disease in one-fifth of patients, thus better redefining the prognosis of such individuals.

Transarterial chemoembolization versus hepatic resection in hepatocellular carcinoma treatment: a meta-analysis.

BackgroundA number of cohort studies have compared the outcomes of transarterial chemoembolization (TACE) and hepatic resection (HR) in the treatment of hepatocellular carcinoma (HCC). However, the effect of TACE versus HR remains controversial. Therefore, we conducted a meta-analysis to assess the effectiveness of TACE and HR in HCC treatment.Materials and methodsPubMed, Embase, Web of Science, Scopus, ClinicalTrials.gov, and Cochrane library were searched from their inception until February 27, 2015 for relevant studies. The literature search was updated on May 25, 2015. Eligible studies were cohort studies comparing the survival outcomes between HCC patients undergoing TACE and HR. The primary outcome was overall survival (OS). Secondary outcomes were the recurrence rate and prognostic factors for OS. The risk ratio (RR) was used for the meta-analysis and was expressed with 95% confidence intervals (CIs).ResultsThis meta-analysis included eleven cohort studies with 6,297 patients, all treated with TACE or HR. Pooled estimates showed that, compared with TACE, HR significantly improved the 3-year OS (RR =0.77; 95% CI, 0.63–0.93; P=0.009). TACE and HR had similar effects on OS after 1 year (RR =0.94; 95% CI, 0.86–1.01; P=0.103), 2 years (RR =0.50; 95% CI, 0.21–1.19; P=0.114), 4 years (RR =0.61; 95% CI, 0.58–1.10; P=0.174), and 5 years (RR =0.77; 95% CI, 0.59–1.01; P=0.06). There was no significant difference between the 3-year (RR =1.31; 95% CI, 0.65–2.64; P=0.457) and 5-year recurrence rates (RR =1.14; 95% CI, 0.69–1.89; P=0.597) in the TACE and HR groups. Age (>65 vs ≤65 years; hazard ratio =0.99; 95% CI, 0.98–1.00; P=0.000), sex (male vs female; hazard ratio =0.79; 95% CI, 0.65–0.96; P=0.02), treatment method (TACE vs HR; hazard ratio =1.90; 95% CI, 1.46–2.46; P=0.000), and Eastern Cooperative Oncology Group performance score (≥1 vs 0; hazard ratio =1.69; 95% CI, 1.22–2.33; P=0.002) were independent predictors for OS.ConclusionThis meta-analysis suggests that the TACE and HR likely have similar effects in the treatment of HCC patients in terms of OS and recurrence rate. However, this conclusion should be interpreted cautiously due to the presence of further subgroup analyses with respect to outcomes in patients with different liver statuses (Barcelona Clinic Liver Cancer stage A or stage B).