• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6673-6678
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• 2014

Background: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. Materials and Methods: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. Results: During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including ${\alpha}$-fetoprotein ${\leq}400ng/mL$ (45.4% vs 16.7%; p=0.006), tumor size ${\leq}5cm$ (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). Conclusions: Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9635-9641
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• 2014

Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.219-224
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• 2016

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver making up more than 80 percent of cases. It is known to be the sixth most prevalent cancer and the third most frequent cause of cancer related death worldwide. Epigenetic regulation constitutes an important mechanism by which dietary components can selectively activate or inactivate target gene expression. The miR-34 family members including mir-34a, mir-34b and mir-34c are tumor suppressor micro RNAs, which are expressed in the majority of normal tissues. Several studies have indicated silencing of miR-34 expression via DNA methylation in multiple types of cancers. Bioactive nutrients like curcumin (Cur) have excellent anticarcinogenic activity and minimal toxic manifestations in biological systems. This compound has recently been determined to induce epigenetic changes. However, Cur is lipophilic and has a poor systemic bioavailability and poor absorption. Its bioavailability is increased through employing dendrosome nanoparticles. The aim of the current study was to investigate the effect of dendrosomal nanocurcumin (DNC) on expression of mir-34 family members in two HCC cell lines, HepG2 and Huh7. We performed the MTT assay to evaluate DNC and dendrosome effects on cell viability. The ability of DNC to alter expression of the mir-34 family and DNA methyltransferases (DNMT1, DNMT3A and 3B) was evaluated using semi-quantitative and quantitative PCR. We observed the entrance of DNC into HepG2 and Huh7 cells. Gene expression assays indicated that DNC treatment upregulated mir34a, mir34b and mir34c expression (P<0.05) as well as downregulated DNMT1, DNMT3A and DNMT3B expression (P<0.05) in both HepG2 and Huh7 cell lines. DNC also reduced viability of Huh7 and HepG2 cells through restoration of miR-34s expression. We showed that DNC could awaken the epigenetically silenced miR-34 family by downregulation of DNMTs. Our findings suggest that DNC has potential in epigenetic therapy of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4421-4427
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• 2015

Objectives: To investigate the prognosis significance of preoperative serum alpha-fetoprotein (AFP) and the correlation with clinicopathological factors of hepatocellular carcinoma (HCC) patients who underwent hepatectomy. Materials and Methods: Clinicopathological data of retrospective analysis were collected for 251 HCC patients undergoing hepatectomy in this study. According to preoperative AFP level, patients were categorized into AFP-negative (0-20ng/mL) and AFP-positive (>20 ng/mL) groups for Kaplan-Meier analysis and Cox proportional hazard regression modeling. Results: The results demonstrated that increased AFP was associated with longer prothrombin time (PTs), liver capsule invasion, low grade differentiation, and late Barcelona Clinic Liver Center (BCLC) stage. Moreover, the female patients had a greater prevalence of increased preoperative AFP than male patients [284.8 (3.975-3167.5) vs (3.653-140.65); Z-2.895, p=0.004]. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 78.1, 57.5, and 40.6 % in the AFP-negative group and 61.8, 37.7, and 31.4 %, respectively, in the AFP-positive group (log-rank test 8.312, p=0.004). The 1-, 3-, and 5-year overall survival (OS) rates were 94.4, 83.8, and 62.3% in the AFP-negative group and 87.2, 60.0, and 36.7%, respectively, in the AFP-positive group. The difference was statistically significant (log-rank test, 16.884, p=0.000). Cox proportional-hazards model identified preoperative AFP to be an independent prognostic predictor of overall survival. Conclusions: Preoperative serum AFP is an independent predictor of prognosis among HCC patients following surgical resection. Female patients have a higher preoperative AFP than their male counterparts.

• Annals of Surgical Treatment and Research
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• v.95 no.6
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• pp.303-311
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• 2018

Purpose: OncoHepa test is a multigene expression profile test developed for assessment of hepatocellular carcinoma (HCC) prognosis. Multiplication of ${\alpha}$-FP, des-${\gamma}$-carboxy prothrombin (DCP) and tumor volume (TV) gives the ${\alpha}$-FP-DCP-volume (ADV) score, which is also developed for assessment of HCC prognosis. Methods: The predictive powers of OncoHepa test and ADV score were validated in 35 patients who underwent curative hepatic resection for naïve solitary HCCs ${\leq}5cm$. Results: Median tumor diameter was 3.0 cm. Tumor recurrence and patient survival rates were 28.6% and 100% at 1 year, 48.6% and 82.9% at 3 years, and 54.3% and 71.4% at 5 years, respectively. The site of first tumor recurrence was the remnant liver in 18, lung in 1, and the peritoneum in 1. All patients with HCC recurrence received locoregional treatment. OncoHepa test showed marginal prognostic significance for tumor recurrence and patient survival. ADV score at 4log also showed marginal prognostic difference with respect to tumor recurrence and patient survival. Combination of these 2 tests resulted in greater prognostic significance for both tumor recurrence (P = 0.046) and patient survival (P = 0.048). Conclusion: Both OncoHepa test and ADV score have considerably strong prognostic power, thus individual and combined findings of OncoHepa test and ADV score will be helpful to guide postresection surveillance in patients with solitary HCCs ${\leq}5cm$.

• Journal of Korean Neurosurgical Society
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• v.59 no.1
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• pp.37-43
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• 2016

Objective : The aim of this multicenter, matched-pair study was to compare the outcomes of stereotactic radiosurgery (SRS) and conventional external radiation therapy (RT) when used as a primary treatment in spine metastasis from hepatocellular carcinoma (HCC). Methods : From 2005 to 2012, 28 patients underwent SRS as the primary treatment in spine metastasis from HCC. Based on sex, age, number of spine metastasis, Child-Pugh classification, interval from original tumor to spine metastasis, and year of treatment, 28 patients who underwent RT were paired. Outcomes of interest were pain relief, progression free survival, toxicities, and further treatment. Results : The perioperative visual analog scale (VAS) decrease was larger in SRS group than in RT group, but the difference was not significant (3.7 vs. 2.8, p=0.13). When pain medication was adjusted, the number of patients with complete (n=6 vs.3) or partial (n=12 vs.13) relief was larger in SRS group than in RT group; however, the difference was not significant (p=0.83). There was no significant difference in progression free survival (p=0.48). In SRS group, 32.1% of patients had 1 or more toxicities whereas the percentage in RT group was 63.0%, a significant difference (p=0.04). Six SRS patients and 7 RT patients received further intervention at the treated segment. Conclusion : Clinical and radiological outcome were not significantly different between the two treatments. Toxicities, however, were more prevalent in the RT group.

• Advances in pediatric surgery
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• v.9 no.1
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• pp.12-18
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• 2003

The purpose of this study is to evaluate children who underwent hepatic resection for primary malignant hepatic tumor in the period from January 1994 to December 2001. A total of 8 patients, seven with hepatoblastoma (HB) and one with hepatocellular carcinoma (HCC), were studied. One HCC was resectable at the initial diagnosis, but five cases of unresectable HB received two cycles of transarterial chemoembolization (TACE) before operation. One patient with an unresectable HB with bone marrow metastasis was operated after one cycle of TACE and one cycle of systemic chemotherapy based on CCG-823F protocol. Another unresectable HB patient received systemic chemotherapy instead of TACE before operation. Postoperative chemotherapy was administered to all of the patients after complete surgical resection on CCG-823F protocol. All 6 patients who underwent TACE and neoadjuvant chemotherapy showed marked reduction in tumor volume and a clear outline of the lesion. Major complication was not noticed. Mean alpha-fetoprotein (${\alpha}$-FP) level at diagnosis, after neoadjuvant chemotherapy and after postoperative chemotherapy was 9,818 (42-35,350), 664, and 10.1 ng/mL, respectively. Half life of the ${\alpha}$-FP after complete resection was 5.1 days (3.0-8.7 days). Median follow up period was 57.1 months (10-97 months) and all the patients are alive with NED. In conclusion, preoperative chemotherapy, especially TACE, is effective, safe, and useful to treat initially unresectable hepatoblastoma, and serial level of the serum ${\alpha}$-FP is a useful tumor marker for diagnosis and monitoring therapeutic responses.

• Journal of The Korean Radiological Technologist Association
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• v.28 no.1
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• pp.145-152
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• 2002

Purpose : Radiofrequency(RF) ablation has known effective treatment in patient with hepatocellular carcinoma(HCC) or hepatic metastases tumor(HMT). The purpose of this study was to evaluate the usefulness of performed patient liver RF ablation guide by CT

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1065-1068
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• 2012

Background: Liver cancer is the most frequent cancer among Thais especially people in northeastern Thailand, but there has as yet been no assessment of trend. The data of all cancers in Khon Kaen can be retrieved from data base of the Khon Kaen Cancer Registry (KKCR) which was established in 1984. Objective: To assess the incidence trend of hepatocellular carcinoma in Khon Kaen, Thailand, between 1990 and 2009. Methods: Population-based cases of liver cancer registered between 1985 and 2009 were retrieved from the KKCR data base and cases with diagnosis of hepatocellular carcinoma (HCC) with the coding C22.0 according to ICD-O were selected. Incidence trends were calculated using the Jointpoint analysis. Results: There were 7,859 cases of HCC during the study period. Males were affected two times more frequently than females. The most common age group of cases was 50 and 69 years (60.3%). Most patients were diagnosed based on radiology imaging (40.6%) while the morphology verification was 7%. The age-standardized rates (ASR) were 13.1 to 49.8 per 100,000 among males and 4.8 to 38.4 per 100,000 among females depending on year of diagnosis since 1985. Remarkably, the ASRs were clearly low during first few years of starting the registration. The overall ASRs of HCC were 30.3 per 100,000 in males (95% CI: 25.9 to 34.6) and 13.1 per 100,000 (95% CI: 10.4 to 15.8) in females. During 1990-2009, the trends in incidences have been decreasing significantly with the annual percent change (APC) of 6.2% per year (95% CI: -7.6 to -4.8) in males and by 6.5% per year in females (95% CI: -8.4 to -4.9). Conclusions: The incidence trends have been decreasing in both sexes. The recent decline in incidence may represent a falling risk.

• Journal of the Korean Society of Radiology
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• v.79 no.5
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• pp.264-270
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• 2018

Purpose: To evaluate the effect of portal hypertension on the tumor recurrence in patients with hepatocellular carcinoma (HCC) and without hepatic decompression following radiofrequency ablation (RFA). Materials and Methods: Treatment-naïve HCC patients within the Milan criteria and with Child-Pugh class A were included in this study, who had performed RFA in our hospital between January 2010 and March 2017. Univariate and multivariate analyses using the Cox proportional hazard model were performed to find the predictors of local or distant tumor recurrence. Results: Overall, 178 patients were included in this study. Median follow-up period was 40.2 months. The difference in the local tumor progression rates depending on the absence or presence of portal hypertension was not statistically significant (p = 0.195). The 1-, 3-, and 5-year distant intrahepatic tumor spread rates were 6.6%, 29.5%, and 537% in patients without portal hypertension, and 23.4%, 51.9%, and 63.6% in patients with portal hypertension, respectively. The difference was statistically significant (p = 0.011). Univariate and multivariate analysis showed that portal hypertension was an independent predictor for distant intrahepatic tumor spread (p = 0.008). Conclusion: For HCC patients with Child-Pugh class A, portal hypertension adversely affected distant intrahepatic tumor progression.