• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.245-251
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• 2015

Objectives: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-${\alpha}$) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone. Methods: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-${\alpha}$ (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP), and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated. Results: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE-IFN-${\alpha}$ group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-${\alpha}$ group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-${\alpha}$ combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS. Conclusions: The use of the TACE and IFN-${\alpha}$ combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8069-8073
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• 2014

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7101-7106
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• 2013

Background: The prognosis of patients with hepatocellular carcinoma (HCC) after curative resection varies greatly. Few studies had investigated the risk factors for early recurrence (recurrence-free time ${\leq}$ 1 year) of hepatitis B virus (HBV)-related HCCs meeting Milan criteria. Methods: A retrospective analysis was performed on the 224 patients with HCC meeting Milan criteria who underwent curative liver resection in our center between February 2007 and March 2012. The overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors for early recurrence were analyzed. Results: After a median follow-up of 33.3 months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The 1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-, 3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha-fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR 2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence (recurrence-free time ${\leq}$ 1-year) of HCC meeting Milan criteria. Conclusions: AFP > 800 ng/ml, multiple tumors and microvascular invasion are independent risk factors affecting early postoperative recurrence of HCC. In addition resection appears capable of replacing liver transplantation in some situations with safety and a better outcome.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2613-2618
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• 2014

Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that $Foxp3^+T$ cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, $CD8^+T$ cells and $Foxp3^+T$ cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in $CD8^+T$ lymphocytes and $Foxp3^+T$ cells in patients with HCC. Methods: $CD8^+T$ cells and $CD3^+Foxp3^+T$ cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in $CD8^+T$ cells and FasL in $CD3^+Foxp3^+T$ cells were evaluated. Serum TGF-${\beta}1$ levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in $CD3^+Foxp3^+T$ cells was then evaluated. Results: The frequency of $CD8^+T$ cells binding annexin V and Fas expression in $CD8^+T$ cells, were all higher in HCC patients than normal controls and the proportion of apoptotic $CD8^+T$ cells correlated with their Fas expression. Serum TGF-${\beta}1$ levels correlated inversely with $CD3^+Foxp3^+T$ cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of $CD8^+T$ cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in $Fas^+CD8^+T$ cells in vitro are required.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7897-7903
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• 2015

Background: To explored the value of 3D C-arm CT (CACT) guidance system in performing radiofrequency ablation (RFA) following transarterial chemoembolizationon (TACE) for hepatocellular carcinomas. Materials and Methods: RFA of hepatocellular carcinomas (HCC) were performed on 15 patients (21 lesions) with the assistance of CACT guidance system. Technical success, procedure time, complications and patient radiation exposure were investigated. The puncture performance level was evaluated on a five-point scale (5-1: excellent-poor). Complete ablation rate was evaluated after two months follow-up using enhanced CT scans. Results: The technical success rate of RFA procedure under CACT navigation system was 100 %. Mean total procedure time was $24.24{\pm}6.53min$, resulting in a mean effective exposure dose of $15.4{\pm}5.1mSv$. The mean puncture performance level rated for CACT guided RFA procedure was $4.87{\pm}0.35$. Complete ablation (CA) was achieved in 20 (95.2%) of the treated 21 tumors after the first RFA session. None of patients developed intra-procedural complications. Conclusions: 3D CACT guidance system enables reliable and efficient needle positioning by providing real-time intraoperative guidance for performing RFA on HCCs.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5397-5402
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• 2013

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

• 호스피스학술지
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• 제7권2호
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• pp.6-14
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• 2007

Purpose: Hepatocellular carcinoma is the 3rd leading cause of cancer death in Korea and its prognosis is very poor. We aimed to investigate the clinical characteristics of terminal patients with hepatocellular carcinoma on admission into a hospice unit, and to know if they had received appropriate hospice and palliative care. Methods: We retrospectively reviewed the medical records in 62 patients with hepatocellular carcinoma who had admitted, received palliative care, and died in a hospice unit between January 2003 and December 2005. Results: The median age of patients was 56.5 years with 50 men(80.65%) and 12 women(19.35%) and gender ratio(male to female) was 417. Child-Pugh class A, B, and C were 6(9.68%), 22(35.38%), and 34(58.84%) respectively. We divided the patients into two groups and compared, the terminal HCC patients with class C as group I and those with class A & B as group 2. The median time from hospice referral to death was significantly short in group 1 with 15.5 days compared to group 2 with 53 days. Statistically more prevalent symptoms in group I were ascites, dyspnea, peripheral edema, and hepatic encephalopathy with abnormal laboratory findings (jaundice, hypoalbuminemia, or renal insufficiency). There, however, was no significant difference in complications and managements during admission between group 1 and 2. Conclusion: Most terminal HCC patients were often accompanied with chronic liver disease. The length of hospice and palliative care for above patients was not enough to attend them. Therefore, we suggest that proper education and information should be provided to physicians, patients, and their family members for effective hospice and palliative care.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5773-5775
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• 2012

Objective: To assess the diagnostic and prognostic value of AFP and des-gamma-carboxyprothrombin (DCP) in combination and alone for hepatocellular carcinoma. Materials and Methods: A case control study carried out in the Department of Biochemistry of Manipal College of Medical Sciences, Pokhara, Nepal between $1^{st}$ January 2010 and $31^{st}$ December 2011. The variables collected were age, gender, BMI, total proteins, albumin, AST, ALT, total bilirubin, DCP, AFP. Approval for the study was obtained from the institutional research ethical committee. Estimation of AFP was performed by ELISA reader for all cases. Analysis was done using descriptive statistics and confidence interval (CI). The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. Results:The mean age of HCC cases was $53.6{\pm}14.93$ yrs. The percentage of females was less than males in both cases (23%) and controls (29%). The specificity of DCP reached 100% when its values was equal or greater than 150 (MAU/ml) for 0, 3, 6, 9, 12 months preceding the diagnosis of HCC. Similarly, the specificity for AFP was also nearly 100% when its value was equal or greater than 200 ng/ml 0, 3, 6, 9, 12 months earlier to the finding of HCC. The specificity of DCP (${\geq}40MAU/mL$) and AFP(${\geq}20$ ng/mL) in combination was 93%, 97%, 95%, 96%, 97% in respect to 0, 3, 6, 9, 12 months prior to the diagnosis of HCC. Conclusion: The combination of both DCP and AFP will improve the finding of initial HCC and the sensitivity of these markers was utmost at the time of HCC identification and noticeably lesser at former time points.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8993-9004
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• 2014

Background: The incidence rate and the treatment costs of hepatocellular carcinoma (HCC) are high, especially in Thailand. Previous studies indicated that early detection by a surveillance program could help by down-staging. This study aimed to compare the costs and health outcomes associated with the introduction of a HCC surveillance program with no program and to estimate the budget impact if the HCC surveillance program were implemented. Materials and Methods: A cost utility analysis using a decision tree and Markov models was used to compare costs and outcomes during the lifetime period based on a societal perspective between alternative HCC surveillance strategies with no program. Costs included direct medical, direct non-medical, and indirect costs. Health outcomes were measured as life years (LYs), and quality adjusted life years (QALYs). The results were presented in terms of the incremental cost-effectiveness ratio (ICER) in Thai THB per QALY gained. One-way and probabilistic sensitivity analyses were applied to investigate parameter uncertainties. Budget impact analysis (BIA) was performed based on the governmental perspective. Results: Semi-annual ultrasonography (US) and semi-annual ultrasonography plus alpha-fetoprotein (US plus AFP) as the first screening for HCC surveillance would be cost-effective options at the willingness to pay (WTP) threshold of 160,000 THB per QALY gained compared with no surveillance program (ICER=118,796 and ICER=123,451 THB/QALY), respectively. The semi-annual US plus AFP yielded more net monetary benefit, but caused a substantially higher budget (237 to 502 million THB) than semi-annual US (81 to 201 million THB) during the next ten fiscal years. Conclusions: Our results suggested that a semi-annual US program should be used as the first screening for HCC surveillance and included in the benefit package of Thai health insurance schemes for both chronic hepatitis B males and females aged between 40-50 years. In addition, policy makers considered the program could be feasible, but additional evidence is needed to support the whole prevention system before the implementation of a strategic plan.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3273-3278
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• 2014

Background: Various studies have evaluated the relationship between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusions have been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whether XRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted from PubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included in the study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluate XRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030 controls were involved in our meta-analysis. The results demonstrated that there was significant association between Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG: OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroup analyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vs GG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) and Caucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934, p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC risk especially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role against HCC among Caucasians.