Postoperative Hepatocellular Carcinoma Research Articles

Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection.

Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2years were included for analysis. Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (P<.0001) and overall survival (P<.0001) after liver resection. The hazard ratio of metformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (P<.05, 95% CI=0.60-0.72) for hepatocellular carcinoma recurrence and 0.79 (P<.05, 95% CI=0.72-0.88) for overall survival after liver resection. The risk reduction in hepatocellular carcinoma recurrence after liver resection was significantly associated with a dose/duration dependent of accumulated metformin usage. Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence.

HBV core promoter mutations and AKT upregulate S-phase kinase-associated protein 2 to promote postoperative hepatocellular carcinoma progression.

Mutations in the hepatitis B virus (HBV) core promoter (CP) have been shown to be associated with hepatocellular carcinoma (HCC). The CP region overlaps HBV X gene, which activates AKT to regulate hepatocyte survival. However, the cooperation between these two cascades in HCC progression remains poorly understood. Here, we assayed virological factors and AKT expression in liver tissues from 56 HCC patients with better prognoses (BHCC, ≥5-year survival) and 58 with poor prognoses (PHCC, <5-year survival) after partial liver resection. Results showed double mutation A1762T/G1764A (TA) combined with other mutation(s) (TACO) in HBV genome and phosphorylated AKT (pAKT) were more common in PHCC than BHCC. TACO and pAKT levels correlated with proliferation and microvascularization but inversely correlated with apoptosis in HCC samples. These were more pronounced when TACO and pAKT co-expressed. Levels of p21 and p27 were decreased in TACO or pAKT overexpressing HCC due to SKP2 upregulation. Levels of E2F1 and both mRNA and protein of SKP2 were increased in TACO expressing HCC. Levels of 4EBP1/2 decreased and SKP2 mRNA level remained constant in pAKT-overexpressing HCC. Therefore, TACO and AKT are two independent predictors of postoperative survival in HCC. Their co-target, SKP2 may be a diagnostic or therapeutic marker.

A preliminary study on molecular markers of DNA copy number aberration for extrahepatic metastasis in patients with hepatocellular carcinoma after surgery

Objective To investigate the molecular markers of DNA copy number aberrations (CNAs) for extrahepatic metastasis in postoperative hepatocellular carcinoma (HCC). Methods The genomic CNA of 66 HCC samples was detected by high-resolution Agilent 244K array comparative genomic hybridization. The correlation between CNAs and extrahepatic metastasis in postoperative HCC was analyzed using univariate and multiple stepwise Cox regression models. Results Univariate analysis showed that gains at 6p21.32, 15q11.2 and 20q12-13.13, and losses at 4q12 and 4q28.1-35.2, together with a history of hypertension, complete tumor capsule, TNM stage, platelet count and prothrombin time, were associated with increased risk of extrahepatic metastasis (all P<0.05). Multiple stepwise Cox regression analyses revealed that 6p21.32 gain (HR=3.65, 95% CI=1.38~9.62) and 4q28.1-35.2 loss (HR=0.24, 95% CI=0.09~0.65), together with a history of hypertension and TNM stage, were independent prognostic markers of extrahepatic metastasis. Survival analysis showed that non-metastatic survival among the 3 groups of HCCs with 6p21.32 gain, with 4q28.1-35.2 loss but without 6p21.32 gain, and without 6p21.32 gain and with 4q28.1-35.2 loss were significantly different (log-rank test, P<0.05). Conclusion Both 6p21.32 gain and 4q28.1-35.2 loss in HCC were two independent prognostic markers of postoperative extrahepatic metastasis. These findings may help to identify patients who are at risk of extrahepatic metastasis after surgery. Key words: Hepatocellular carcinoma; Extrahepatic metastasis; Array comparative genomic hybridization; Copy number aberration

Association of preoperative EpCAM Circulating Tumor Cells and peripheral Treg cell levels with early recurrence of hepatocellular carcinoma following radical hepatic resection.

BackgroundThis study was carried out to determine the prognostic significance of preoperative peripheral epithelial cell adhesion molecule- positive (EpCAM+) circulating tumor cell (CTC) and T regulatory (Treg) cell levels in hepatocellular carcinoma (HCC) patients for the prediction of postoperative recurrence following curative resection.MethodsA total of 49 patients about to undergo curative resection for HCC were recruited into the study. PCR and FACS were used to detect the preoperative levels of EpCAMmRNA+ CTCs and CD4+CD25+Foxp3+ Treg cells. The prognostic value of EpCAMmRNA+ CTCs, CD4+CD25+Foxp3+ Treg cells, and other clinicopathological factors were analyzed by applying the Kaplan–Meier method and the multivariate Cox proportional hazards model.ResultsThe number of EpCAMmRNA+ CTCs and Treg/CD4+ cells showed significant correlation as prognostic factors of postoperative HCC recurrence: EpCAMmRNA+ CTC ≥ 2.22 (P = 0.001) and Treg/CD4+ ≥ 5.07 (P = 0.045), with EpCAMmRNA+ CTC ≥ 2.22 (P = 0.003, HR = 6.668) being the most important indicator. Patients with high CTC/Treg levels showed a significantly higher risk of developing postoperative HCC recurrence than those with low CTC/Treg levels (66.7 % vs. 10.3 %, P < 0.001). The high CTC/low Treg group also presented higher 1-year recurrence rates compared with the low CTC/low Treg level group (50.0 % vs. 10.3 %, P = 0.004).ConclusionsElevated EpCAMmRNA+ CTC and Treg/CD4+ levels were associated with early recurrence of HCC, indicative of poor clinical outcome. The combined detection of EpCAMmRNA+ CTC and Treg/CD4+ may therefore provide a novel prognostic predictor for HCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2526-4) contains supplementary material, which is available to authorized users.

Androgen receptor mitigates postoperative disease progression of hepatocellular carcinoma by suppressing CD90+ populations and cell migration and by promoting anoikis in circulating tumor cells.

PurposeAlthough hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence.Experimental DesignCTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome. AR knockout was introduced in two mouse models of spontaneous HCC (carcinogen- and hepatitis B virus-related HCC) to delineate the role that AR plays in HCC recurrence. Biological systems analysis was used to investigate the cellular and molecular mechanisms.ResultsWe found that the expression of AR in CTCs was negatively associated with HCC recurrence/progression after hepatectomy. Our results suggest that AR-mediated suppression of HCC recurrence/progression is governed by a three-pronged mechanism. First, AR suppresses the expression of CD90 in CTCs by upregulating Histone 3H2A. Second, AR suppresses cell migration at the transcriptome level. Third, AR promotes anoikis of CTCs via dysregulation of cytoskeletal adsorption.ConclusionsThe results indicate that AR expression may be the gatekeeper of postoperative HCC recurrence. Therefore, targeting AR in presurgical down-staging procedures may serve as a secondary prevention measure against HCC recurrence in the future.

A Preoperative Measurement of Serum MicroRNA-125b May Predict the Presence of Microvascular Invasion in Hepatocellular Carcinomas Patients

The high recurrence rate remains a major problem that strongly influenced the prognosis of hepatocellular carcinoma (HCC) patients who received hepatectomy. The presence of microvascular invasion (MVI) is regarded as the most important risk factor that contributes to the postoperative recurrence. Our previous study has hinted that serum microRNA-125b (miR-125b) was associated with MVI. The aim of the present study was to identify whether serum miR-125b can serve as a biomarker to reliably predict microvascular invasion (MVI) preoperatively. MiR-125b was quantified in 108 HCC patients’ serum before they received surgery by quantitative real-time PCR (qRT-PCR). Our results revealed that MVI was associated with relapse free survival (RFS) of postoperative HCC patients; surgical margin width was associated with postoperative RFS in MVI present patients, but not in the patients without MVI. Multivariate analysis revealed that miR-125b, tumor size and AFP were the independent predictive factors associated with MVI in this cohort (P = .001, .001, .003, respectively). The probability of the predictive accuracy of miR-125b was 76.95% (51.32% specificity and 87.50% sensitivity), which was almost equal to the classifier established by combination of AFP and tumor size (78.82% probability, 65.63% specificity and 84.21% sensitivity). Furthermore, the combination of tumor size, AFP and miR-125b yielded a ROC curve area of 86.68% (72.37% specificity and 84.38% sensitivity). Our study indicated that serum miR-125b can be used to predict MVI of HCC patients before they received hepatic resection. Therefore, miR-125b can potentially guide individualized treatment, which helps HCC patients, with or without MVI, to benefit from different surgical approach.

Preoperative muscle steatosis is a novel prognostic predictor after hepatectomy for hepatocellular carcinoma

Introduction: The quality of skeletal muscle, shown as muscle steatosis, has recently attracted much attention as a new parameter of sarcopenia, but its impact on outcomes after hepatectomy for hepatocellular carcinoma (HCC) remains unclear. Methods: We performed a retrospective analysis of 500 patients undergoing hepatectomy for HCC between April 2005 and March 2015. The quality and quantity of skeletal muscle were evaluated by intramuscular adipose tissue content (IMAC) and psoas muscle mass index (PMI) using preoperative CT imaging, respectively. Correlations of IMAC with other factors, overall and recurrence-free survival rates in patients classified according to IMAC or PMI, and risk factors for poor outcomes after hepatectomy were analyzed. Results: Patients with high IMAC showed older age (P < 0.001), higher body mass index (P < 0.001), higher indocyanine green retention test at 15 min (P = 0.048), and more operative blood loss (P = 0.019). The overall and recurrence-free survival rates were significantly lower in patients with high IMAC than in patients with normal IMAC (P < 0.001, P = 0.012, respectively). On the other hand, the overall and recurrence-free survival rates were not significantly different between high PMI and low PMI groups (P = 0.486, P = 0.307, respectively). On multivariate analyses, preoperative high IMAC was the significant risk factor for death (hazard ratio [HR] = 2.848; P < 0.001) and for HCC recurrence (HR = 1.383; P = 0.007) after hepatectomy. Conclusions: Preoperative muscle steatosis was closely correlated with postoperative mortality and HCC recurrence.

Abnormal expression of circulating nuclear factor-κB in hepatocellular carcinoma and reversal of multidrug resistance through intervening its gene transcription

To investigate the expressions of nuclear factor-κB (NF-κB) and P-glycoprotein (P-gp) in patients with liver diseases and the effects and mechanism of intervening NF-κB activation on multiple drug resistance (MDR) reversal. The levels of circulating NF-κB and P-gp expression were quantitatively detected in 294 patients with liver diseases by using enzyme-linked immunosorbent assay. NF-κB gene transcription in human HepG2 cells was intervened by specific siRNA with/without doxorubicin treatment. Levels of protein or gene expression were analyzed by Western blotting or fluorescence quantitative polymerase chain reaction (PCR). The dynamic increase of circulating NF-κB and P-gp expressions were observed during patients from chronic hepatitis to cirrhosis to hepatocellular carcinoma (HCC) development. The levels of serum NF-κB and P-gp expression in HCC were significantly higher (P<0.001) than those in cirrhosis, chronic hepatitis, and normal controls. The expression levels of serum NF-κB and P-gp were significantly associated with HBV infection (P<0.05), elevated after interventional chemotherapy with higher frequency or prolonged therapy, and significantly decreased in the post-operative HCC (P<0.001). Both expressions in HepG2 cells were significantly higher after adding doxorubicin in the cell cultures. After the cells were transfected with siRNA, the NF-κB expression was down-regulated at mRNA or protein level with higher sensitivity to doxorubicin. The over-expressions of NF-κB and P-gp are closely associated with MDR formation; intervention of NF-κB activation can inhibit P-gp expression, and enhance the sensitivity to anti-cancer drug and reverse MDR of HCC.

Tumour-suppressive role of PTPN13 in hepatocellular carcinoma and its clinical significance.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality and carries a dismal prognosis. The present study aimed to identify the tumour-suppressive role and clinical implications of PTPN13 in HCC progression. We tested the effects of PTPN13 expression in proliferation, invasion, epithelial-mesenchymal transition and associated pathways in HCC cell lines in vitro. Furthermore, its clinical relevance was evaluated in a tissue microarray analysis of samples from 282 HCC patients. Various HCC cell lines expressed relatively low PTPN13 protein levels in vitro. PTPN13 overexpression significantly inhibited the progression of HCC cells, possibly by inhibiting epithelial-mesenchymal transition through inactivation of the EGFR/ERK signalling pathway. Tissue microarray analysis revealed that high PTPN13 expression was correlated with a favourable prognosis in postoperative HCC patients. This study demonstrated the tumour suppressor, PTPN13, as an alternative therapeutic target for HCC.

The STORM trial and beyond: narrowing the horizon of adjuvant sorafenib for postoperative hepatocellular carcinoma.

The STORM trial and beyond: narrowing the horizon of adjuvant sorafenib for postoperative hepatocellular carcinoma.

The Preference for Anterior Approach Major Hepatectomy: Experience Over 3 Decades and a Propensity Score-Matching Analysis in Right Hepatectomy for Hepatocellular Carcinoma.

Surgical treatment for primary hepatocellular carcinoma (HCC) has progressed enormously over time. The aim of this study was to analyze the evolution of surgical techniques and outcomes of patients undergoing major right hepatectomy (RH) over the last few decades.A retrospective review of 557 consecutive patients who had undergone RH for HCC between January 1982 and December 2011 was performed. Patients were categorized into subgroups and analyzed according to period and surgical approach to hepatectomy. Based on a propensity score-matching model, the surgical approach in patients in the second period was also analyzed in terms of anterior approach (AA) and conventional approach (CA)-RH.Tumor factors remained the most important prognostic factors related to postoperative HCC recurrence throughout the 2 periods examined in this study. Comparison of patients selected by a propensity score-matching model showed that AA-RH led to significantly better outcomes including recurrence-free survival (RFS) (P = 0.011) and overall survival (OS) (P = 0.012) in patients with HCC as compared with CA-RH. The 5-year RFS and OS were 33.4% and 52.2% after AA-RH, and 21.0% and 36.5% after CA-RH.Major hepatectomy has evolved into a safe procedure that can be performed with confidence. RH by an AA has shown several advantages over CA-RH, and can thus be recommended as the standard procedure for liver resection in patients who require right hepatectomy.

Low expression of B-cell-associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis.

The aim of the present study was to investigate the prognostic value of B-cell associated protein 31 (BAP31) in human primary hepatocellular carcinoma (HCC). BAP31 levels were evaluated by immunohistochemistry on tissue microarrays. The integral optical density, representing the expression level of BAP31 in each tissue sample, was calculated with image-pro plus. Immunohistochemical analysis of BAP31 levels in 74 paired HCC tissues and peritumoral non-cancerous tissues showed that BAP31 expression was significantly higher in HCC tumour tissues (P = 0.025). The prognostic value of BAP31 in HCC was evaluated in 234 cases in a training cohort and in 63 cases in a validation cohort. The expression level of BAP31 was significantly correlated with overall survival (OS) in both the training cohort and the validation cohort. The lower the level of BAP31 expression in HCC tissue, the poorer the prognosis. Univariate and multivariate analyses showed that the expression level of BAP31 in HCC was an independent prognostic factor for OS in both the training cohort and the validation cohort. BAP31 expression is an independent prognostic factor for OS of patients with postoperative HCC, and low expression levels of BAP31 in HCC may indicate poor outcomes of HCC patient after surgical resection.

High-powered microwave ablation of larger hepatocellular carcinoma: evaluation of recurrence rate and factors related to recurrence

To evaluate the safety and efficacy of high-powered (80-100W) percutaneous microwave ablation (MWA) at a frequency of 2450±10MHz for treating larger hepatocellular carcinoma (HCC) and to predict the risk factors of local recurrence after high-powered MWA. The study was approved by the Institutional Review Board, and informed consent was waived because of the retrospective study design. Forty-five patients with a total of 60 lesions received high-power (80-100W) MWA at a frequency of 2450±10MHz through a percutaneous approach that was guided by ultrasound. Of the 60 lesions with a maximum tumour measuring 3-8cm, 46 lesions were 3-5cm and 14 were 5-8cm. The complete ablation rates, local recurrence rates, complications, and short-term survival were analysed. Ten possible risk factors for local recurrence were analysed. The complete ablation rates were 82.61% for the first ablation and 100% for the second ablation for 3-5cm lesions. The complete ablation rates were 64.29% (82.61% versus 64.29%, p=0.037) for the first ablation and 85.71% (100% versus 85.71%, p=0.055) for the second ablation for 5-8cm lesions. Local recurrence was observed in 11 out of the 45 (24.44%) successfully treated patients. The 1-year and 2-year survival rates were 95.56% (43/45) and 86.67% (39/45), respectively. No procedure-related mortality was observed and no major bleeding, liver rupture, or liver abscesses occurred. Univariate analysis showed that a positive correlation existed between the number of lesions (p=0.022), proximity to the risk area (p=0.001), pre-ablation alpha-fetoprotein (AFP) levels (p=0.025), hepatitis B virus (HBV)-DNA replication (p=0.027) and local recurrence. Multivariate analysis identified HBV-DNA (p=0.031) and proximity to the risk area (p=0.039) as the independent prognosis factors causing postoperative HCC local recurrence. High-powered MWA of larger hepatocellular carcinomas appears to be a safe and effective treatment. HBV-DNA and proximity to the risk area appear to be independent predictors of local tumour recurrence.

Preoperative intramuscular adipose tissue content is a novel prognostic predictor after hepatectomy for hepatocellular carcinoma.

Sarcopenia has been shown to be an independent predictor of lower disease-free and overall survival in various kinds of diseases. The quality of skeletal muscle has recently attracted much attention as a new parameter of sarcopenia. We performed a retrospective analysis of 477 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between April 2005 and August 2014. The quality of skeletal muscle was evaluated by intramuscular adipose tissue content (IMAC) using preoperative computed tomography (CT) imaging. The impact of IMAC on outcomes after hepatectomy for HCC was analyzed. Patients with high IMAC showed older age, higher body mass index, higher indocyanine green retention test at 15 min, and more operative blood loss. The overall and recurrence-free survival rates were significantly lower in patients with high IMAC than in patients with normal IMAC (P < 0.0001, P = 0.0012, respectively). Multivariate analysis showed that high IMAC was the significant risk factor for death (hazard ratio [HR] = 2.942; P < 0.0001) and for HCC recurrence (HR = 1.529; P = 0.0007) after hepatectomy. Preoperative quality of skeletal muscle was closely correlated with postoperative mortality and HCC recurrence. IMAC could be incorporated into new selection criteria for hepatectomy for HCC.

MiR-615-3p expression level in bone marrow is associated with tumor recurrence in hepatocellular carcinoma.

The significance of disseminated tumor cells (DTCs) in bone marrow (BM) on tumor recurrence has not been investigated in patients with hepatocellular carcinoma (HCC). The aim of te present study was to clarify the molecular characteristics of DTCs that affect postoperative recurrence based on microRNA (miRNA) expression profiles in clinical HCC patients undergoing curative resection. DTCs were prospectively collected from the BM of preoperative HCC patients using immunomagnetic beads and subjected to miRNA microarray analysis. Microarray analysis of nine HCC patients (n=5 patients with postoperative HCC recurrence, n=4 patients without HCC recurrence) demonstrated that miR-615-3p is significantly upregulated in the DTCs of patients with recurrence compared to the DTCs from patients without recurrence. In vitro experiments demonstrated that the miR-615-3p expression level is significantly correlated with malignant characteristics in HCC cells. These data suggest that miR-615-3p in DTCs may play an important role in postoperative HCC recurrence, which suggests that miR-615-3p is a potential target molecule for regulating postoperative HCC recurrence.

Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival.

Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.

Antiviral therapy improves postoperative survival in patients with hepatocellular carcinoma: a randomized controlled trial.

A randomized controlled trial was conducted to find out whether antiviral therapy in patients with hepatitis B-related hepatocellular carcinoma (HCC) improves long-term survival after hepatic resection. Despite advances in surgery and in multidisciplinary treatment, there is still no effective adjuvant treatment to prevent HCC recurrence after R0 resection for HCC. Whether antiviral therapy is useful in reducing postoperative HCC recurrence is unclear. Between May 2007 and April 2008, patients who received R0 hepatic resection for HBV-related HCC were randomly assigned to receive no treatment (the control group, n = 100) or antiviral therapy (adefovir 10 mg/d, the antiviral group, n = 100). The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.0%, 50.3%, 46.1% and 84.0%, 37.9%, 27.1%, respectively. The corresponding overall survival rates for the 2 groups were 96.0%, 77.6%, 63.1% and 94.0%, 67.4%, 41.5%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.026, P = 0.001). After adjusting for the confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.651 [95% confidence interval (CI): 0.451-0.938; P = 0.021] and 0.420 (95% CI: 0.271-0.651; P < 0.001). Antiviral therapy was an independent protective factor of late tumor recurrence (HR = 0.348, 95% CI: 0.177-0.687; P = 0.002) but not of early tumor recurrence [hazard ratio (HR) = 0.949, 95% CI: 0.617-1.459; P = 0.810]. In patients with hepatitis B-related HCC, adefovir antiviral therapy reduced late HCC recurrence and significantly improved overall survival after R0 hepatic resection.

Reevaluation of glypican-3 as a prognostic marker in HCC using X-tile software.

Glypican-3 (GPC3) is a widely used immunohistochemical marker for hepatocellular carcinoma (HCC); however, its prognostic value is unclear. Immunohistochemical evaluation of GPC3 expression was performed on 300 postoperative HCC tissue samples with paired adjacent non-tumor tissues on tissue microarray sections. The integral optic density, representing the expression level of GPC3 in each HCC sample, was calculated using Image-Pro Plus. The outcome-based cut-point optimization was performed using X-tile software. GPC3 was highly expressed in HCC tissues compared with adjacent non-tumor tissues. The expression level of GPC3 was significantly correlated with overall survival (OS) and time to recurrence (TTR). The lower the level of GPC3 expression in HCC tissue, the poorer the observed prognosis. Univariate and multivariate analyses showed that the expression level of GPC3 in HCC was an independent prognostic factor for both OS and TTR. In conclusion, GPC3 expression is an independent prognostic factor for postoperative HCC, and low expression levels of GPC3 in HCC may indicate poor outcome.

Retrobulbar metastasis and intracranial invasion from postoperative hepatocellular carcinoma: A case report and review of the literature

Hepatocellular carcinoma (HCC) is the most common malignant cancer of the liver and the third ranking cause of cancer-related mortality worldwide. Following the diagnosis of HCC, intrahepatic and extrahepatic metastasis patients account for ~50–75% of all HCC cases, lung and regional lymph nodes metastasis are the most common; metastasis to bone, skin and adrenal glands are rare, orbit metastasis and intracranial invasion are extremely rare. The present study reports the rare case of a patient with HCC that metastasized to the head. The patient presented with retrobulbar and intracranial invasion, and sub-scalp extension. Based on imaging findings, the lesion was initially misdiagnosed as meningioma, however, postoperative pathological examinations resulted in a definitive diagnosis of HCC metastasis. Based on the present case and a review of the relevant literature published since 2009, the current study recommends that metastasis must be considered when diagnosing retrobulbar head lesions in patients with HCC, regardless of contradictory imaging findings and other clinical indicators, which may closely mimic the original head lesion.

Long term survival analysis of primary hepatocarcinoma patients received transcatheter arterial chemoembolization plus chemotherapy after radical resection

To evaluate the survival of hepatocellular carcinoma (HCC) patients received prophylactic use of transcatheter arterial chemoembolization (TACE) after radical resection. One hundred and forty-three cases of HCC from Ningbo No.2 Hospital were divided into intervention prevention group, chemotherapy prevention group and comprehensive prevention group according to different methods of HCC prevention. All patients were followed-up for more than 5 years after TACE, chemotherapy (FOLPOX4) or TACE+ FOLPOX4. Cox regression model of multiple factors analysis was used for analyzing impact factors on HCC prognosis. Survival rate was compared with Kaplan-meier method. Alpha-fetoprotein (AFP) was negatively correlated with the survival time of patients, as an independent risk factor with the regression coefficient of 0.01 and the relative risk of 1.00. Prevention of postoperative increased survival time of patients with HCC, which was a protective factor. The regression coefficient for comprehensive prevention was -2.37 and the relative risk was 0.07, the weight of comprehensive prevention on lifetime was higher than that of other two prevention methods, followed by TACE prevention group. One-year, 2-year, 3-year cumulative survival rates in comprehensive prevention group were 78.35%， 69.16%， 24.43%， that in TACE prevention group were 76.87%， 62.48%， 24.72%， and that in chemotherapy prevention group were 62.23%， 43.22%， 19.54%， respectively. AFP was negative correlation with the survival time of postoperative HCC patients, monitored which of postoperative HCC patients can provide a reference for effect and prognosis of surgery. Application of TACE in HCC patients with postoperative effective in reducing mortality, which prolong the survival time of HCC patients might be extended further by combined chemotherapy based on its own advantages and disadvantages.