Prognostic Factor For Hepatocellular Carcinoma Research Articles

Prognostic factors of hepatocellular carcinoma survival after radiofrequency ablation: A US population-based study.

To determine the survival outcome and prognostic factors of hepatocellular carcinoma (HCC) survival in patients who underwent radiofrequency ablation (RFA). The Surveillance, Epidemiology and End Results (SEER) database was queried: There were 2588 HCC patients from 2004 to 2012 who underwent RFA. The Kaplan-Meier curves and the multivariate Cox regression analysis were used to assess the prognostic factors. With a median follow-up of 20 months, the 1-, 3- and 5-year overall survival (OS) rates were: 83%, 51% and 33%. Patients with a tumor size ≤5 cm in diameter had a better 5-year OS, as compared to patients with a tumor size >5 cm. The 5-year OS was significantly higher among patients with a normal level of alpha-fetoprotein (AFP), compared with those having elevated AFP. In an adjusted multivariate Cox regression analysis, those with ≥60 years of age (HR: 1.19; 95% CI 1.05-1.36), non-Asian race (HR: 1.53; 95% CI 1.30-1.81), tumor size >5 cm (HR: 1.43; 95% CI 1.24-1.65), elevated AFP (HR: 1.42; 95% CI 1.22-1.64), American Joint Committee on Cancer (AJCC) stages II-III (HR: 1.30; 95% CI 1.14-1.48) and the year of diagnosis from 2004-2007 (HR: 1.22; 95% CI 1.07-1.40) were significantly associated with a poor prognosis. Age, race, tumor size, AFP level, AJCC stage and year of diagnosis were prognostic factors for OS in HCC patients who underwent RFA.

Analysis of surgical treatment and prognostic factors for hepatocellular carcinoma with portal vein tumor thrombus

Background: Hepatocellular carcinoma (HCC) was the most common primary malignant liver tumor. The portal vein thrombosis (PVTT) of 10–40% were detected when HCC is exactly diagnosed. The patients whose PVTT existed in main branch of portal vein had poor prognosis. Whether hepatectomy could improve the survival rate of patients of HCC with PVTT was currently unknown. This study was to explore the prognosis and affecting factors of HCC with PVTT after liver resection.

Effect of nucleos(t)ide analog antiviral treatment on the pathological differentiation and prognosis of hepatitis B virus-related hepatocellular carcinoma

Objective To explore the effect of nucleos(t)ide analog (NA) antiviral treatment on the pathological differentiation of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and the prognostic factors of HCC. Methods Totally 127 patients with HBV-related HCC who were hospitalized and received partial hepatectomy in First Affiliated Hospital of Harbin Medical University from March 2007 to November 2013 were included in this study. Sixteen cases received antiviral treatment before operation and the remaining 111 cases had no history of NA treatment. The differences of histopathological grading were compared between the two groups. Twenty-nine patients received antiviral treatment for the first time after surgery, and the rest 82 patients did not. All these patients were followed up for survival and recurrence. Multivariate analysis was used to explore the prognostic factors for HCC. The categorical variables were analyzed by χ2 test or Fisher exact test. Survival rate was compared with Log-rank test. Univariate or multivariate Cox regression analysis was used to explore the related factors of survival. Results The proportions of well-, moderately- or poorly-differentiated HCC in patients with antiviral treatment before surgery were 18.75%, 68.75% and 12.5%, respectively. Whereas the proportions in those without treatment were 16.22%, 66.67% and 17.11%, respectively. There was no significant difference in histopathological grading of HCC between the two groups (χ2=0.224, P=0.885). The overall median survival time was 39 months. The 6-month, 1- and 2-year survival rates were 91.7%, 77.5% and 59.3%, respectively. The 6-month, 1- and 2-year survival rate of postoperative antiviral treatment were 96.3%, 92.4% and 78.5%, respectively, which were significantly higher than those of no antiviral treatment group (85.9%, 70.0% and 48.5%, respectively; χ2=6.967, P=0.008). Univariate analysis showed that tumor number, size, portal vein transfer, AFP level, postoperative antiviral treatment, histopathological grading, TNM staging, BCLC staging, γ-GT and PTA were prognostic factors for postoperative HCC survival. Multivariate analysis showed that AFP level (HR=1, 95%CI: 1.0004—1.002, P=0.004), postoperative antiviral treatment (HR=0.38, 95%CI: 0.38—0.15, P=0.04) and BCLC stage (B vs A: HR=1.55, 95%CI: 0.76—3.18; C vs A: HR=3.63, 95%CI: 1.31—10.09, P=0.04) were independent prognostic factors. Conclusions Preoperative antiviral treatment has no impact on the histopathological grading of HCC. BCLC stage, AFP level and postoperative antiviral treatment are independent prognostic factors for HBV-related HCC. Key words: Liver Neoplasms; Hepatitis B; Antiviral agents; Histopathological; Prognostic factors

The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection.

A simple, inexpensive, and readily available prognostic index is highly needed to accurately predict the prognosis of hepatocellular carcinoma (HCC). This study aimed to develop a simple prognostic index using routine laboratory tests, alkaline phosphatase-to-platelet count ratio index (APPRI), to predict the likelihood of postoperative survival in HCC patients.A total of 246 patients with HCC undergoing curative resection were retrospectively analyzed. Cutoff point for APPRI was calculated using receiver operating characteristic curve analysis, and then the patients were divided into the low-APPRI group (APPRI ≤ 4.0) and the high-APPRI group (APPRI > 4.0). The influences of APPRI on disease-free survival (DFS) and overall survival (OS) were tested by the Kaplan–Meier method, and multivariate analysis using Cox regression. Elevated APPRI was associated with age, cirrhosis, and aspartate aminotransferase (AST) in HCC. Univariate analysis showed that APPRI > 4.0, tumor size >6 cm, multiple tumors, Barcelona-clinic liver cancer stages B to C, and AST > 40 U/L were significant predictors of worse DFS and OS. A multivariate analysis suggested that APPRI > 4.0 was an independent factor for DFS (hazard ratio [HR] = 1.689; 95% confidence interval [CI], 1.139–2.505; P = 0.009) and OS (HR = 1.664; 95% CI, 1.123–2.466; P = 0.011). Preoperative APPRI > 4.0 was a powerful prognostic predictor of adverse DFS and OS in HCC after surgery. The APPRI may be a promising prognostic marker for HCC after surgical resection.

Low PLCE1 levels are correlated with poor prognosis in hepatocellular carcinoma.

BackgroundPrevious reports show that phospholipase C epsilon-1 (PLCE1) expression is positively correlated with esophageal squamous cell carcinoma and gastric cardia adenocarcinomas; however, the expression of PLCE1 in hepatocellular carcinoma (HCC) and its correlation with clinical outcome still remain unclear. The aim of this study was to explore the expression of PLCE1 in HCC tissue and to determine whether PLCE1 was a prognostic factor for HCC patients.Materials and methodsPLCE1 levels in 20 paired HCC tissues and corresponding paracarcinomatous tissues was investigated by quantitative real-time polymerase chain reaction and Western blot assays. In addition, protein levels of PLCE1 in one normal liver epithelial cell and four HCC cell lines were examined using Western blot assay. Moreover, immunohistochemistry was applied to determine the expression of PLCE1 in HCC and corresponding surrounding tissues from 90 patients. Statistical analyses were used to examine the association between PLCE1 levels and clinicopathological features.ResultsWe found that the expression of PLCE1 in tumor tissues was significantly lower than those in paracarcinomatous tissues at both mRNA and protein levels (P<0.05). We also determined that PLCE1 protein expression levels were lower in HCC cell lines than normal liver epithelial cells (P<0.05). Notably, immunohistochemical assay showed that PLCE1 expression was significantly low in HCC tissues compared with the adjacent normal liver tissues (40% vs 18.9%; P<0.05). Besides, PLCE1 levels were negatively correlated with tumor capsulae, vascular invasion, Edmondson grade, alpha-fetoprotein, and tumor-node-metastasis stage (P<0.05). Univariate analysis revealed that lower level expression of PLCE1 was significantly associated with poorer overall survival (OS) rate (P<0.001) and disease-free survival rate (P<0.001). Multivariate analysis revealed that low PLCE1 level was an independent poor prognostic factor of OS and recurrence-free survival (P<0.001 and P=0.003, respectively).ConclusionIn brief, our results revealed that decreased PLCE1 expression was associated with tumor progression in HCC and may function as a promising biomarker for HCC prognosis.

Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.

As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p=0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.

Knockdown of Histone Methyltransferase hSETD1A Inhibits Progression, Migration, and Invasion in Human Hepatocellular Carcinoma.

Our aim was to study the expression of human SET domain containing protein 1A (hSETD1A) in hepatocellular carcinoma patients and its relationship with human hepatocellular carcinoma cell function. A total of 30 patients with hepatocellular carcinoma were enrolled in this study. The expression of hSETD1A was detected by real-time polymerase chain reaction (PCR) and Western blotting. The immortalized normal human liver cell line including SMMC-7721 was subjected to real-time PCR for hSETD1A mRNA. Furthermore, hSETD1A-small hairpin RNA (shRNA) was used to knock down hSETD1A expression in SMMC-7721 cells. Cell proliferation, cell apoptosis, and cell migration were determined by CCK8, flow cytometry, and Transwell assays. The positive expression rate level of hSETD1A mRNA and protein in liver carcinoma tissues was 73.33%. hSETD1A knockdown using a specific hSETD1A-shRNA inhibited cell proliferation and promoted cell apoptosis in SMMC-7721 cells. It was also found that downregulation of hSETD1A inhibited cell migration ability but did not affect cell invasion. In conclusion, the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma.

EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through β-catenin/ID2 pathway

Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated β-catenin at Ser675, blocked β-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-β-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing β-catenin/ID2 activation, and was an independent prognostic factor in PDAC.

Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70years and older with hepatocellular carcinoma.

The present study investigated the effect of sarcopenia on short- and long-term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70years of age and older. Patient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70years, and 70years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long-term survival data were analyzed. Sarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70years. Overall survival and disease-free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis. This retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence-free survival after hepatectomy in patients 70years of age and older with HCC.

Postoperative Low Absolute Lymphocyte Counts may Predict Poor Outcomes of Hepatocellular Carcinoma After Liver Resection.

Background:The absolute lymphocyte counts (ALCs) have been reported as one of worse prognostic factors for hepatocellular carcinoma (HCC) patient after liver transplantation. The aim of this study was to assess the influence of ALCs on the outcomes of patients with hepatitis B virus (HBV)-related HCC within the Milan criteria following liver resection.Methods:Data of patients with HCC within the Milan criteria who received liver resection between January 2007 and June 2013 were reviewed, and perioperative ALCs were carefully monitored. All potential risk factors were statistically analyzed by uni- and multi-variate analyses. The receiver operating characteristic (ROC) curve was used to determine the optimal ALCs cut-off value to predict HCC recurrence after liver resection.Results:A total of 221 patients were enrolled in the current study. During the follow-up period, 106 patients experienced recurrence, and 38 patients died. Multivariate analysis suggested microvascular invasion (MVI), a tumor grade ≥2, and a low postoperative ALCs in the 1st postoperative month increased the incidence of postoperative recurrence, besides, MVI, intraoperative transfusion, and a low postoperative ALCs in the 1st postoperative month were associated with poor overall survival (OS). An ROC analysis showed that a cut-off value of 1.5 × 109/L for ALCs in the 1st postoperative month predicted postoperative recurrence. The 5-year recurrence-free survival (RFS) and OS rates of patients with low postoperative ALCs were 34.5% and 64.8%, respectively, which were significantly lower than those of patients with high postoperative ALC (58.5% for RFS and 86.5% for OS).Conclusion:Low ALCs in the 1st postoperative month may be associated with high recurrence incidence and poor OS for patients with HBV-related HCC within the Milan criteria after liver resection.

Blood Neutrophil-to-Lymphocyte Ratio Predicts Tumor Recurrence in Patients with Hepatocellular Carcinoma within Milan Criteria after Hepatectomy.

PurposeThe systemic inflammation biomarker, Neutrophil-to-Lymphocyte Ratio (NLR), has been reported as one of the adverse prognostic factors for hepatocellular carcinoma (HCC) patient. The purpose of this study was to evaluate whether NLR could predict the risk of recurrence and death for the HCC patient, according to Milan criteria after hepatectomy.Materials and MethodsRetrospective analysis was performed on a database of HCC patients who underwent hepatectomy between March 2001 and December 2011. The cutoff value of NLR was decided by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate regression analyses were performed to identify predictive factors of recurrence and death.ResultsA total of 213 patients were included in the present study. The median follow-up period was 48 months. One hundred and seven patients were experienced tumor recurrence; forty of them recurred within 12 months (early recurrence). NLR ≥1.505, albumin ≤3.75 g/dL, microvascular invasion and high grade of cirrhosis were found to be independent factors for adverse recurrence-free survival in multivariate regression analysis. And NLR ≥1.945 was also found as a prognosis factor for early recurrence by univariate regression analysis.ConclusionElevated preoperative NLR can be easily obtained and reliable biomarker for assessing the tumor recurrence and early recurrence of Milan criteria HCC after the initial hepatectomy.

Microvascular invasion in hepatocellular carcinoma.

Microvascular invasion is a crucial histopathologic prognostic factor for hepatocellular carcinoma. We reviewed the literature and aimed to draw attention to clinicopathologic and imaging findings that may predict the presence of microvascular invasion in hepatocellular carcinoma. Imaging findings suggesting microvascular invasion are disruption of capsule, irregular tumor margin, peritumoral enhancement, multifocal tumor, increased tumor size, and increased glucose metabolism on positron emission tomography-computed tomography. In the presence of typical findings, microvascular invasion may be predicted.

Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment.

To investigate the long-term survival and prognostic factors in hepatocellular carcinoma (HCC) patients undergoing radiofrequency ablation (RFA) as a first-line treatment. From 2000 to 2013, 316 consecutive patients with 404 HCC (1.0-5.0 cm; mean: 3.2 ± 1.1 cm) underwent ultrasonography-guided percutaneous RFA as a first-line treatment. There were 250 males and 66 females with an average age of 60.1 ± 10.8 years (24-87 years). Patients were followed for 1 year to > 10 years after RFA (234, 181, 136, and 71 for 3, 5, 7, and 10 years, respectively). Overall local response rates and long-term survival rates were assessed. Survival results were generated using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model. In total, 548 RFA sessions were performed and major complications occurred in 10 sessions (1.8%). Local tumor progression and/or new tumor development were observed in 43.3% (132/305) of the patients during the follow-up period. Overall 5- and 10-year survival rates were 49.7% and 28.4%, respectively. Based on multivariate analysis, three factors were identified as independent prognostic factors for overall survival: Child-Pugh classification (HR = 4.054, P < 0.001), portal vein hypertension (HR = 2.743, P = 0.002), and tumor number (HR = 2.693, P = 0.003). The local progression-free 5- and 10-year survival rates were 42.7% and 19.5%. In addition to the Child-Pugh classification and the number of tumors, the number of RFA sessions (HR = 1.550, P = 0.002) was associated with local progression-free survival. RFA can achieve acceptable outcomes for HCC patients as a first-line treatment, especially for patients with Child-Pugh class A, patients with a single tumor and patients without portal vein hypertension.

RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma

Methylation of the Ras-association domain family 10 (RASSF10) promoter region correlates with clinicopathological characteristics and poor prognosis in several human cancers. Here, we examined RASSF10 expression in hepatocellular carcinoma (HCC) and its role in hepatocarcinogenesis. RASSF10 mRNA and protein levels were downregulated in both HCC cell lines and patient tissue samples. In patient tissues, low RASSF10 levels correlated with hepatocirrhosis, poor tumor differentiation, tumor thrombus and Barcelona Clinic Liver Cancer stage, and were indicative of increased tumor recurrence and reduced patient survival. Low RASSF10 expression was associated with promoter hypermethylation, which was in turn associated with polycyclic aromatic hydrocarbon and aflatoxin B1 exposure, but not DNA methyltransferase expression. Overexpression of RASSF10 in HCC cell lines suppressed cell growth and colony formation, and induced apoptosis by up- or down-regulating specific Bcl-2 family proteins. RASSF10 overexpression increased pro-apoptotic Bax and Bad levels, but decreased anti-apoptotic Bcl-2 and Bcl-xl expression. Overexpression also inhibited tumor formation in nude mice and reduced cell migration and invasion by inhibiting the epithelial-mesenchymal transition. RASSF10 knockdown promoted cell growth. Our results show that RASSF10 is frequently hypermethylated and down-regulated in HCC and can potentially serve as a useful biomarker predictive of HCC patient prognosis.

Modifiable Prognostic Factors of Hepatocellular Carcinoma in Patients with Non-Surgical Treatment.

Background & aimsCurrent hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment.MethodsAll HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years.ResultsA total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1st or 2nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1st treatment (OR: 2.17, 95% CI: 1.35–3.48), incomplete 2nd treatment (2.01, 1.27–3.17) and absence of anti-viral agents (1.68, 1.09–2.59) were independent poor prognostic factors.ConclusionComplete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible.

Downregulation of lncRNA-ATB correlates with clinical progression and unfavorable prognosis in pancreatic cancer.

Long noncoding RNAs (lncRNAs) have been shown to play critical roles in the development and progression of diseases. lncRNA activated by transforming growth factor beta (TGF-β) (lncRNA-ATB) was discovered as a prognostic factor in hepatocellular carcinoma, gastric cancer, and colorectal cancer. However, little is known about the role of lncRNA-ATB in pancreatic cancer. This study aimed to assess lncRNA-ATB expression in pancreatic cancer and explore its role in pancreatic cancer pathogenesis. Quantitative real-time polymerase chain reaction was performed to detect lncRNA-ATB expression in 150 pancreatic cancer tissues and five pancreatic cancer cell lines compared to paired adjacent normal tissues and normal human pancreatic ductal epithelial cell line HPDE6c-7. The correlations between lncRNA-ATB expression and clinicopathological characteristics and prognosis were also analyzed. We found that lncRNA-ATB expression was decreased in pancreatic cancer tissues and pancreatic cancer cell lines. Low lncRNA-ATB expression levels were significantly correlated with lymph node metastases (yes vs. no, P = 0.009), neural invasion (positive vs. negative, P = 0.049), and clinical stage (early stage vs. advanced stage, P = 0.014). Moreover, patients with low lncRNA-ATB expression levels exhibited markedly worse overall survival prognoses (P < 0.001). Multivariate analysis indicated that decreased lncRNA-ATB expression was an independent predictor of poor prognosis in pancreatic cancer patients (P = 0.005). In conclusion, lncRNA-ATB may play a critical role in pancreatic cancer progression and prognosis and may serve as a potential prognostic biomarker in pancreatic cancer patients.

Total Tumor Volume As a Prognostic Factor in Hepatocellular Carcinoma Treated by Radioembolization With Yttrium-90 Glass Microspheres

Total Tumor Volume As a Prognostic Factor in Hepatocellular Carcinoma Treated by Radioembolization With Yttrium-90 Glass Microspheres

Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis

Tumoural portal vein thrombosis (PVT) is a major prognostic factor in hepatocellular carcinoma (HCC). The efficacy of sorafenib, the only treatment approved at an advanced stage, is limited. Based on previous data, selective internal radiation therapy (SIRT), or (90)Y radioembolization, seems an interesting option. We aimed to compare both treatments in this population. We retrospectively compared patients treated in two centres for HCC with tumoural PVT. We compared overall survival (OS) between patients treated with SIRT and patients treated with sorafenib. Analyses were performed before and after 1:1 matching with a propensity score for controlling indication bias, using a Cox proportional hazards model. A total of 151 patients were analysed, 34 patients treated with SIRT and 117 patients treated with sorafenib only. In the whole population, SIRT was associated with a higher median OS as compared with sorafenib: 18.8 vs 6.5months (log-rank p < 0.001). There was an imbalance of baseline characteristics between patients treated by SIRT and sorafenib, which justified patient matching with use of a propensity score: 24 patients treated with SIRT could be matched with 24 patients treated with sorafenib. OS was estimated with a median of 26.2 vs 8.7months in patients treated with SIRT vs sorafenib, respectively (log-rank p = 0.054). Before and after patient matching, the adjusted hazard ratio related to treatment by SIRT was estimated at 0.62 [95% confidence interval (CI) 0.39-0.97] (p = 0.037) and 0.40 (95% CI 0.19-0.82) (p = 0.013), respectively. SIRT seems more effective than sorafenib in patients presenting with HCC and tumoural PVT. This hypothesis is being tested in prospective randomized trials.

Clinical Impact of Anatomical Liver Resection for Hepatocellular Carcinoma with Pathologically Proven Portal Vein Invasion.

Portal vein invasion (PVI) is known to be a poor prognostic factor for hepatocellular carcinoma (HCC) patients. Anatomical liver resection (ALR) is a preferable procedure for treating HCC. However, the effect of ALR for HCC with PVI has not been fully evaluated. The aim of this study is to investigate the survival benefit of ALR for HCC patients with or without pathologically proven portal vein invasion (pPVI). Curative hepatic resection was performed for a single HCC in 313 patients. The patients were divided into two groups according to the absence or presence of pPVI (absence: n = 216, presence: n = 97). These groups were then subclassified by the surgical procedures employed (ALR or non-ALR), and the clinical characteristics and stratified prognoses were compared according to the surgical procedure between the subgroups. Uni- and multivariate analyses were performed to explore the significant prognostic factors. Among the patients without pPVI, there was no significant difference in postoperative survival between the groups. However, among the patients with pPVI, both the 5-year overall and recurrence-free survival rates in the ALR group were significantly higher than those in the non-ALR group (46.1 % vs. 16.3 %; p = 0.0019 and 33.8 % vs. 0 %; p = 0.0010). Multivariate analyses revealed that tumor differentiation and intraoperative blood loss (IOB) were associated with postoperative survival in patients without pPVI. On the other hand, in patients with pPVI, ALR, serum AFP level, and IOB were associated with postoperative survival. ALR confers a survival benefit for HCC patients with pPVI.

ITPKA expression is a novel prognostic factor in hepatocellular carcinoma.

BackgroundInositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has recently been found to be implicated in the tumor progression of various cancers. However, the expression and the prognostic value of ITPKA in hepatocellular carcinoma (HCC) remains unexplored. The aim of this study is to investigate the clinical significance of ITPKA expression in HCC.MethodsWe determined the expression level of ITPKA in 135 cases of HCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR. The correlation between ITPKA expression and prognosis of HCC patients was further evaluated by univariate and multivariate analysis. Multivariate analysis of the prognostic factors was performed with Cox proportional hazards model.ResultsUp-regulation of ITPKA occurred in 48.9 % of primary HCCs compared with their nontumor counterparts (P < 0.001). In addition, high expression of ITPKA was significantly associated with vascular invasion (P = 0.001) and TNM stage (P = 0.005). Kaplan–Meier analysis showed that the 5-year overall survival (OS) and relapse-free survival (RFS) rate in the group with high expression of ITPKA is poorer than that in low expression group (32.2 and 26.8 % versus 59.2 and 57.7 %). Univariate and multivariate analyses revealed that ITPKA was an independent prognostic factor for OS and RFS. Moreover, Stratified analysis revealed that its prognostic significance still existed within the subgroup of patients with early clinical stage (TNM stage I) or normal serum AFP level (≤25 μg/L).ConclusionOur data indicated that ITPKA expression was significantly up-regulated in HCC and could serve as a potential novel prognostic biomarker for HCC patients after surgery.