Overall Survival Of Hepatocellular Carcinoma Patients Research Articles

Parametric response mapping cut-off values that predict survival of hepatocellular carcinoma patients after TACE.

Parametric response mapping (PRM) is a novel image-analysis technique applicable to assess tumor viability and predict intrahepatic recurrence of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). However, to date, the prognostic value of PRM for prediction of overall survival in HCC patients undergoing TACE is unclear. The objective of this explorative, single-center study was to identify cut-offvalues for voxel-specific PRM parameters that predict the post TACE overall survival in HCC patients. PRM was applied to biphasic CT data obtained at baseline and following 3 TACE treatments of 20 patients with HCC tumors ≥ 2cm. The individual portal venous phases were registered to the arterial phases followed by segmentation of the largest lesion, i.e., the region of interest (ROI). Segmented voxels with their respective arterial and portal venous phase density values were displayed as a scatter plot. Voxel-specific PRM parameters were calculated and compared to patients' survival at 1, 2, and 3years post treatment to identify the maximal predictive parameters. The hypervascularized tissue portion of the ROI was found to represent an independent predictor of the post TACE overall survival. For this parameter, cut-off values of 3650, 2057, and 2057voxels, respectively, were determined to be optimal to predict overall survival at 1, 2, and 3years after TACE. Using these cut points, patients were correctly classified as having died with a sensitivity of 80, 92, and 86% and as still being alive with a specificity of 60, 75, and 83%, respectively. The prognostic accuracy measured by area under the curve (AUC) values ranged from 0.73 to 0.87. PRM may have prognostic value to predict post TACE overall survival in HCC patients.

Hepatocellular carcinoma-related cyclin D1 is selectively regulated by autophagy degradation system.

Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy‐selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33‐238R) and phosphorylation site (T286A) mutants, lentivirus‐mediated silencing autophagy‐related 5 (ATG5), autophagy‐related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy‐selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. Conclusion: Taken together, our data demonstrate that autophagic degradation machinery and the cell‐cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141‐154).

PRMT5 promotes cell proliferation by inhibiting BTG2 expression via the ERK signaling pathway in hepatocellular carcinoma.

Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, has roles in cell growth regulation and cancer development. However, the role of PRMT5 in hepatocellular carcinoma (HCC) progression remains unclear. Here, we showed that PRMT5 expression was frequently upregulated in HCC tissues, and its expression was inversely correlated with overall survival in HCC patients. PRMT5 knockdown markedly inhibited in vitro HCC proliferation and in vivo tumorigenesis. We revealed that the mechanism of PRMT5‐induced proliferation was partially mediated by BTG downregulation, leading to cell cycle arrest during the G1 phase in HCC cells. Ectopic BTG2 overexpression decreased HCC growth, caused cell cycle arrest at the G1 phase, and downregulated Cyclin D1 and Cyclin E1 protein expression. Furthermore, we found that PRMT5‐induced ERK phosphorylation regulated BTG2 expression in HCC cells, whereas pretreatment with a selective ERK1/2 inhibitor (PD184352) significantly reversed the effect of PRMT5 on BTG2 expression. Our results indicated that PRMT5 promotes HCC proliferation by downregulating BTG2 expression via the ERK pathway.

Prognosis of hepatic failure with the albumin-bilirubin model for hepatocellular carcinoma after stereotactic body radiotherapy with and without transplant.

384 Background: The Albumin-Bilirubin (ALBI) model is a validated prognostic assessment of cirrhosis in hepatocellular carcinoma (HCC), stratifying patients to grades 1(ALBI-1), 2(ALBI-2), or 3(ALBI-3). We reported that ALBI distinguishes patients at higher risk for hepatic failure(HF) after stereotactic body radiotherapy (SBRT) within the Child Pugh(CP) A population. We now apply the ALBI model to both CP-A and CP-B patients after SBRT with or without orthotropic liver transplant (OLT), and assess its prognostic capability of overall survival (OS) and HF relative to the CP model. Methods: From 2009-2017, 68 patients with 81 HCC lesions and CP-A (45) or CP-B (23) cirrhosis completed SBRT in this IRB approved study. The median dose was 45 Gy (35 - 57 Gy) in 4-7 fractions. Initial ALBI and CP scores were measured against OS and progression of CP class, which was recorded every 3-4 months. Median follow-up = 18 months. Results: The median age = 62 and tumor size = 3.5 cm (1.1 Ð 11 cm). 26 patients were ALBI-1, 31 ALBI-2, and 11 ALBI-3 prior to SBRT. For all patients, 2-year local control was 96%. 1 and 2 year OS was 77% and 54%, disease free survival was 71% and 40%, and freedom from CP progression was 71% and 56%, respectively. OS was significantly different between ALBI-1, ALBI-2, and ALBI-3 patients (P = 0.01), as was progression of CP class (P<0.001). When stratified by initial CP class, there were no significant differences in survival or CP progression [Table 1]. In a subset of 37 CP-A and 15 CP-B without OLT, rates of progressive cirrhosis were better predicted by ALBI (P<0.001) than CP class (P=0.09). Conclusions: Compared to the CP model, the ALBI index more precisely predicted HF and OS in HCC patients for both early and intermediate cirrhosis. Its application may help better select candidates for OLT after SBRT, who may be at higher risk for HF than initially predicted. [Table: see text]

Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma.

Mediator complex subunit 15 (MED15) is a coactivator involved in the regulated transcription of RNA polymerase II-dependent genes and serves an oncogenic role in numerous types of cancer. However, the expression and function of MED15 in hepatocellular carcinoma (HCC) remain unknown. In the present study, the aim was to investigate the expression and clinical significance of MED15 in HCC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analysis revealed that MED15 mRNA and protein levels were significantly upregulated in HCC tissues compared with those in the corresponding adjacent non-tumor liver tissues. Furthermore, analyzing data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and GSE14520 datasets revealed a significant correlation between MED15 expression and the tumor size (P=0.033), Barcelona Clinic Liver Cancer stage (P=0.031), α-fetoprotein levels (P=0.002) and metastasis risk (P=0.001). Furthermore, patients with high MED15 expression levels had a shorter survival time compared with those with low MED15 expression levels (P<0.05). Univariate and multivariate analyses further revealed that MED15 may be an independent prognostic factor for the overall survival of HCC patients (hazard ratio, 1.762; 95% confidence interval, 1.077–2.882; P<0.05). In addition, MED15 expression was positively associated with hypoxia-inducible factor 1α expression in the TCGA-LIHC and GSE14520 datasets (P<0.01). In conclusion, the data reported in the present study indicated that MED15 is overexpressed in HCC and may represent a novel prognostic biomarker for patients with HCC.

Outcomes of surgery for hepatocellular carcinoma with tumor thrombus in the inferior vena cava or right atrium.

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is extremely poor. We reviewed the recent surgical treatments and outcomes of this form of advanced HCC. TT is classified into three types according to its anatomic location relative to the heart: the inferior hepatic type (type I), where the TT is in the IVC below the diaphragm; the superior hepatic type (type II), where the TT is in the IVC above the diaphragm, but still outside the RA; and the intracardiac type (type III), where the TT is above the diaphragm and has entered the RA. Type I can be treated relatively easily by standard radical hepatectomy. For type II, the intrathoracic IVC is approached via the abdominal cavity and an incision in the diaphragm with total hepatic vascular exclusion (THVE). For type III, hepatectomy plus thrombectomy is generally performed under cardiopulmonary bypass. If the TT is only just inside the RA, THVE can be performed by mobilizing the liver caudally. The median overall survival of HCC patients with TT in the IVC or RA, who undergo curative resection, is 19.0-30.8months. As postoperative recurrence is likely to develop, even after curative surgery, effective postoperative adjuvant chemotherapy is required.

Overexpression of SCAMP3 is an indicator of poor prognosis in hepatocellular carcinoma.

SCAMP3, an isoform of the secretory carrier membrane proteins (SCAMPs) family, is a membrane-trafficking protein involved in endosome transport. Previous microarray data showed that SCAMP3 mRNA is highly expressed in hepatocellular carcinoma (HCC). In this study, the expression and clinical significance of SCAMP3 in 100 pairs of HCC and adjacent normal tissue were investigated. siRNA transfection was performed to silence SCAMP3 expression in HCC cells. The MTS assay and flow cytometry were used to detect the proliferation, cell cycle progression of HCC cells. Compared with adjacent normal tissues, SCAMP3 expression was dramatically increased in HCC tissues demonstrated by Western blotting (P < 0.05). In immunohistochemistry, compared with the adjacent normal tissues, SCAMP3 was detected in 96% of the HCC samples with a significant increase in intensity and number of stained cells (P < 0.05). Also, high SCAMP3 expression was found in 86% of the HCC samples (P < 0.05). The increased SCAMP3 expression was significantly correlated with vascular invasion (P = 0.004) and tumor stage (P = 0.001). Univariate and multivariate survival analyses showed that the expression of SCAMP3 was an independent prognostic factor of overall survival of HCC patients. Knockdown of SCAMP3 expression led to suppression of cell proliferation and blockage of cell cycle of HCC cells. In conclusion, our present study suggested that SCAMP3 may serve as a promising prognostic biomarker and molecular target of HCC and further investigation is warranted.

Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma

BackgroundAutophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1’s capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. MethodsThe expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. ResultsThe expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P=0.035), high levels of serum AFP (P=0.049), more frequency of node metastasis (P=0.015), later TNM stage (P=0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P=0.021), while LC3B were suggested to be negatively related with patients’ PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P=0.002) and shorter 5-year progression free survival (PFS)(P=0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. ConclusionULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.

Hepatocellular carcinoma treated with sorafenib: Arterial tumor perfusion in dynamic contrast-enhanced CT as early imaging biomarkers for survival

ObjectivesTo investigate whether hepatic perfusion CT yields early imaging biomarkers predictive of the prognosis of hepatocellular carcinoma (HCC) patients treated with sorafenib. MethodsWe evaluated 36 HCC patients who underwent hepatic perfusion CT before- and one week after sorafenib therapy. We measured arterial and portal perfusion in the hepatic tumor and liver parenchyma [(AP)(PP)tumor], [(AP)(PP)liver]. The perfusion ratio was calculated by dividing the post- by the pre-sorafenib value. The effect of each value on the overall survival rate was analyzed with the Cox proportional hazards model; statistically significant parameters were subjected to receiver operating characteristic analysis based on median survival after sorafenib administration to determine the overall survival rate with the Kaplan-Meier method. ResultsPre-APtumor was significantly associated with the overall survival rate (hazard ratio (HR) and 95% confidence interval (CI), 0.16 and 0.02-0.84, p=0.03). The APtumor ratio tended to be associated with the overall survival rate (HR and 95% CI, 2.94 and 0.94-7.88, p=0.06). The overall survival rate was higher in patients with pre-APtumor>71.7mL/min/100mL, and with APtumor ratio≦1.1 (p<0.01 and 0.03, respectively, in Kaplan-Meier method with log-rank). ConclusionHepatic perfusion CT yields early imaging biomarkers for predicting overall survival in HCC patients treated with sorafenib.

Preoperative prediction of hepatocellular carcinoma with portal vein tumor thrombus based on conventional data.

Hepatocellular carcinoma (HCC) has a high predilection with portal vein tumor thrombosis (PVTT). However, part of the PVTT type can be found only under the microscopy, which was namely as type I0. The objective of this study was to establish a simple and inexpensive non-invasive model to predict the presentation of PVTT at HCC patients. A total of 815 HCC patients were retrospectively evaluated and randomly assigned into 2 groups: the training group (n = 408) and validation group (n = 407). A new index model, namely WγAL, was built to predict the presence of PVTT in the training subjects and was further validated in the validation subjects. At the optimal cutoff of 8.90, WγAL identified patients with a hazard ratio (HR) of 7.139 for the presence of PVTT. The area under receiver operating characteristic (AUROC) of WγAL was 0.795 (sensitivity: 71.9%; specificity: 78.6%) for differentiation between PVTT and non-PVTT patients in the training group. The AUROC of WγAL in differentiating patients with PVTT type I0 from non-PVTT patients was 0.748 (sensitivity: 72.1%; specificity: 68.4%) with an HR of 5.355. In addition, WγAL > 8.90 was significantly associated with large tumors, multiple tumor numbers, TNM stage III-IV, metastasis, and overall survival in HCC patients. The novel predictive model represents a simple and inexpensive model that can identify the presence of PVTT in HCC patients with a high degree of accuracy, with important clinical significance in the future therapeutic management of HCC patients.

Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib.

Neutrophil-to-lymphocyte ratio (NLR) is considered a prognostic factor in patients with hepatocellular carcinoma (HCC). Our aim is to investigate the prognostic significance of NLR in patients with HCC treated with sorafenib.ResultsMedian follow-up time was 7 months. Patients were mostly in the intermediate (27.3%) or advanced (72.7%) BCLC stages, 38.6% had vascular invasion and 27.5% extrahepatic disease. A large proportion (38.9%) had been previously treated with TACE. Liver function was preserved: 65.8% were classed as Child A. Median overall survival was 7.7 months (95% CI: 5.8–9.6). In univariate analysis, vascular invasion (P = 0.004), ECOG-PS ≥ 1 (P < 0.001), high bilirubin (P < 0.001), clinical ascites (P = 0.036), BCLC stage (P = 0.004), no previous TACE (P = 0.041) and NRL ≥ 2.3 (P = 0.005) were predictors of poor survival. Skin toxicity (P = 0.039) or hypertension (P = 0.033) during treatment were related to better survival. In multivariate analysis NLR ≥ 2.3 [HR 1.72 (95% CI: 1.03–2.71)], hyperbilirubinemia [HR 3.42 (95% CI: 1.87–6.25)] and ECOG-PS ≥ 1 [HR 1.97 (95% CI: 1.19–3.26)] were found as independent indicators of poor overall survival. Dermatologic adverse effects were an indicator of good overall survival [HR 0.59 (95% CI: 0.38–0.92)].Material and MethodsOne hundred and fifty-four consecutive HCC patients treated with sorafenib in four different Spanish hospitals between August 2005 and October 2013 were analysed. Clinical, laboratory, and tumour features were obtained. Survival was calculated from the moment sorafenib treatment was initiated. Log-rank and Cox regression were used to analyse the ability of NLR to predict survival.ConclusionsNLR is an independent prognostic indicator for overall survival in HCC patients treated with sorafenib.

MiR-122 inhibits epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Snail1 and Snail2 and suppressing WNT/β-cadherin signaling pathway

The downregulation of microRNA-122 (miR-122) had been reported to be associated with tumor invasion and metastasis in hepatocellular carcinoma (HCC). However, the underlying mechanisms of miR-122 involved in epithelial-mesenchymal transition (EMT) still need to be investigated. In the study, we demonstrated that miR-122 was significantly downregulated in HCC tissues compared with adjacent normal tissues. MiR-122 expression was closely correlated with tumor size, vascular invasion and American Joint Committee on Cancer (AJCC) stage of HCC patients. Kaplan-Meier survival curve and log rank test demonstrated that lower miR-122 predicted poor Disease-free survival (DFS) and overall survival (OS) time in patients. Univariate and multivariate Cox analysis confirmed that tumor size, vascular invasion, American Joint Committee on Cancer (AJCC) stage and lower miR-122 expression levels were independent risk factors for DFS or OS in HCC patients. Function assays demonstrated that upregulation of miR-122 inhibited the cell proliferation, colony formation and cell invasion in HCC cells, however, downregulation of miR-122 promoted cell proliferation, colony formation and cell invasion in HCC cells. Moreover, we demonstrated that increased miR-122 expression levels in HCC cells inhibited epithelial-mesenchymal transition (EMT) by suppressing the expression of ZEB1/2, Snail1/2, N-cadherin, Vimentin and upregulating the E-cadherin expression. However, downregulation of miR-122 caused an opposite effects. Mechanisms study found that miR-122 overexpression inhibited the EMT process by targeting Snail1 and Snail2 and regulated their expression levels in HCC cells. In addition, we also revealed that upregulated miR-122 expression suppressed the Wnt/β-catenin signaling pathway. Taken together, our results indicated that miR-122 may be a biomarker for predicting prognosis of HCC and therapeutic target for HCC patients.

Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas

Pigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial–mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.

Long non-coding RNA CARLo-5 promotes tumor progression in hepatocellular carcinoma via suppressing miR-200b expression.

Long non-coding RNAs (lncRNAs) play key roles in cancer initiation and progression. The aim was to investigate the biological functions and clinical significance of long non-coding RNA CARLo-5 in hepatocellular carcinoma (HCC). QRT-PCR was performed to investigate CARLo-5 expression in HCC tissues and cells. Kaplan-Meier curve and multivariate analysis validated the association between CARLo-5 expression and overall survival (OS) in HCC patients. Cell proliferation and invasion was performed by CCK8 cell proliferation, cell colony formation and transwell invasion assays. Western-blot assay was performed to evaluate the protein expression of Twist1, ZEB1, E-cadherin and Vimentin. Tumor xenografts were performed to evaluate the effect of CARLo-5 on tumor growth in vivo. RNA Immunoprecipitation (RIP) and Chromatin Immunoprecipitation (ChIP) were also performed. Our results showed that CARLo-5 expression was significantly higher in HCC tissues and upregulated CARLo-5 expression was closely correlated with tumor size and advanced tumor stage. Kaplan-Meier curve and multivariate analysis validated that higher CARLo-5 expression predicted a poor prognosis for HCC patients and was an independent risk factor for OS in HCC patients. In vitro, knockdown of CARLo-5 inhibited cell proliferation, colony formation, cell invasion and inhibited the cell epithelial-mesenchymal transition (EMT) by up-regulating the E-cadherin expression and down-regulating Twist1, ZEB1 and vimentin expression in HCC cells. Furthermore, we demonstrated that CARLo-5 inhibited the miR-200b expression via EZH2. In vivo, knockdown of CARLo-5 significantly inhibited the tumor growth. Thus, our results indicated that CARLo-5 represented a novel tumor biomarker and therapeutic target for HCC.

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients.

Advantages of Laparoscopic Radiofrequency Ablation Over Percutaneous Radiofrequency Ablation in Hepatocellular Carcinoma

Inoperable hepatocellular carcinoma (HCC) can be treated with laparoscopic radiofrequency ablation (LRFA), which is generally a more accurate and accessible procedure than percutaneous RFA (PRFA). However, few studies have compared survival outcomes between LRFA and PRFA in patients with HCC. This study aimed to compare the efficacy of LRFA and PRFA for HCC treatment. Patients who underwent PRFA or LRFA as an initial treatment modality between April 2005 and April 2016 were enrolled in this study. The overall and recurrence-free survival rates were examined for each patient. Additionally, propensity score matching was performed for both groups. The baseline characteristics of patients in the PRFA and LRFA groups showed several minor differences. Multivariate analysis showed that the RFA method was not a critical determinant of recurrence-free or overall survival (p=0.069 and p=0.406). Among patients who underwent RFA as the initial treatment modality, there was no significant effect between either RFA procedures on survival. After propensity score matching, univariate analysis showed a significant difference in overall survival between PRFA and LRFA (p=0.031). Multivariate analysis showed that LRFA is a strong factor that contributed to an improved overall survival in HCC patients (hazard ratio 0.108, p=0.040). Furthermore, our data showed that LRFA was able to limit multiple intrahepatic recurrences, as well as prevent marginal recurrence. LRFA appears to be superior to PRFA in terms of survival. LRFA may help reduce mortality in HCC patients.

Circulating microRNAs panel as a diagnostic tool for discrimination of HCV-associated hepatocellular carcinoma

Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve the overall survival of HCC patients. However, current diagnostic markers are compromised and limited by their low sensitivity and specificity. In this work, circulating microRNAs (miRs) were utilized as a diagnostic tool to test their efficiency to segregate HCC and hepatitis C virus (HCV)-infected patients from healthy subjects. Nine HCC-related miRs (miR-21, miR-30c, miR-93, miR-122, miR-125b, miR-126, miR-130a, miR-193b and miR-222) were analyzed by Real-Time PCR in 86 serum samples; 34 HCC and 52 HCV patients in addition to 25 healthy subjects. The sensitivity and specificity of these miRs were assessed. Our results demonstrated that the median serum level of seven miRs was significantly reduced (P ranges from <0.01 to<0.001) in HCC patients whereas nine miRs were reduced (P<0.001) in HCV compared to healthy controls. Receiver operating characteristic (ROC) curve analyses had shown high diagnostic accuracy (AUC=1.0) when seven and nine combined miRs were considered in HCC and HCV groups, respectively compared to their counterparts. However, a combination of differentially expressed miRs did not improve the discriminatory power (AUC=0.742) when HCC compared to non-HCC groups. miR-122 showed the highest sensitivity and specificity to stratify HCC and HCV versus normal individuals and HCC versus HCV patients. We conclude that differentially expressed miRs in the serum of HCV and HCC patients can be utilized as surrogate and non-invasive biomarker for segregation of HCV and HCC patients from healthy subjects.

Effect of tumor volume and radiation dose on the prognosis of hepatocellular carcinoma patients treated with whole body gamma knife

Objective To examine the effects of gross tumor volume (GTV) and radiation dose on the prognosis of hepatocellular carcinoma (HCC) patients treated with whole body gamma knife. Methods The clinical data of 69 HCC patients who underwent body gamma knife treatment from January 2012 to June 2015 in the Radiotherapy Center of the PLA General Hospital were retrospectively reviewed. Based on a 50% or 60% isodose coverage of the planning target volume (PTV), patients were treated with a radiation dose of 4-5 Gy per fraction, and a total marginal dose of 36-50 Gy (median dose 45 Gy). Short-term efficacy, overall survival (OS), and the adverse effect of the treatment were evaluated. The optimal cut-off tumor volume was identified using the receiver operating characteristic curve, and survival was determined by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional hazards regression model, respectively. Results The overall short-term response rate of the 69 patients was 67%. The 1-and 2-year OS rates were 62% and 40%, respectively, with a median survival of 18.6 months. The multivariate analysis showed that gross tumor volume (GTV) 93 cm3(P=0.665). Conclusions GTV is an independent prognostic factor for overall survival of HCC patients. Although high-dose radiotherapy provides survival benefits to patients with small GTV, it is not necessarily suitable for patients with large GTV. Key words: Liver neoplasms/stereotactic radiotherapy; Gross tumor volume; Prognosis

Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients.

Urotensin II and the associated urotensin II receptor (UTR) are important in the carcinogenesis of hepatocellular carcinoma (HCC). However, the clinical significance of UTR remains to be elucidated. The aim of the present study was to investigate if UTR exhibits the potential to act as a biomarker to predict the prognosis of HCC patients. The effects of UTR on motility and invasion of HCC cells were additionally investigated. UTR expression levels were determined by immunohistochemistry, in 83 HCC patients that previously underwent curative liver resection. The association between UTR levels and clinicopathological data were analyzed. In vitro, the expressions of UTR in QSG-7701, BEL-7402 and MHCC-97H cell lines were determined via western blotting. Small interfering (si)RNA was used to downregulate UTR in BEL-7402 and MHCC-97H cell lines, and the effects of UTR on tumor cell motility were tested by Transwell assay. UTR expression was associated with tumor number, size, histology and tumor node metastasis/Barcelona Clinic Liver Cancer HCC stage. UTR expression levels were additionally associated with recurrence-free and overall survival in HCC patients by Kaplan-Meier curve analysis (P<0.0001). In vitro, UTR expression levels were increased in BEL-7402 and MHCC-97H cell lines, compared with QSG-7701 (P<0.05). siRNA-mediated silencing of the UTR gene significantly inhibited cell motility in BEL-7402 and MHCC-97H cells. The results indicated that UTR may be regarded as a novel biomarker to predict outcomes following radical liver resection and as a potential therapeutic target to inhibit invasion and metastasis of HCC.

Predictive Factors Determining Survival in Ambulatory Cirrhotic HCC Patients & Survival Analysis Using ALBI & Child Score

Background and Aim: Identifying accurate prognostic indicators of overall survival (OS) in Hepatocellular carcinoma (HCC) allows care provider to counsel Individual patients and utilize optimum resources. In this study we aim to find out predictive factors determining survival in ambulatory cirrhotic HCC patients & further assess survival using ALBI & CHILD Score. Methods: In this observational study at MCH Thiruvananthapuram, All patients with diagnosis of HCC from January 2011 to December 2016 were studied who received standard of care and predictors of survival were studied with parameters measured before any treatment and within 6 weeks of diagnosis. A total of 202 were included and predictive factors in terms of OS were studied. Results: In our cohort of 202 cirrhotic patients, 164 were males and 38 were females. 43% were HBV related, 20% NASH and 17% Ethanol related. 36% CHILD A, 33% CHILD B and 30% CHILD C. 11%, 55% and 34% were ALBI grade 1, 2 and 3 respectively calculated using an online calculator by Stanford university, 13%, 27%, 28%, 31% were BCLC A, B, C and D respectively. 88% died on follow up. On Multivariate regression ALBI grade, CHILD status, Serum creatinine, serum albumin, INR, Serum Bilirubin, Platelet count, % Neutrophils were identified as factors affecting OS in HCC patients. Visual Inspection of the resulting Kaplain Meir survival curves shows equal good discrimination between the 3 ALBI groups & the CHILD grades. Median survival was 17, 6.6, 1.6 months in ALBI grade 1, 2 and 3 respectively & 10, 5, and 2 months in CHILD A, B and C respectively. Conclusion: ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting (Figure 1 and Table 1).Table 1Multivariate Cox Regression Analysis.VariableHRP-valueCIALBI Grade2.4230.0021.368–4.291CHILD PUGH STATUS1.370.050.991–2.328Serum creatinine1.5190.0550.991–2.328Serum Albumin0.3530.0000.212–0.588INR3.4540.0001.854–6.436Serum Bilirubin1.110.0011.043–1.182Platelet10.0151–1 Open table in a new tab The authors have none to declare.