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ABSTRACT: BACKGROUND AND AIM: Although tumor differentiation is a known prognostic factor after the treatment of hepatocellular carcinoma (HCC), there have not been any studies on the prognostic significance of tumor differentiation in HCC with heterogeneous histologic grades. In this study, we attempted to ascertain whether the major or the worst grade in mixed histologic type HCC determines the prognosis after liver resection. METHODS: From January 1996 to March 2010, a total of 724 patients underwent curative resection of HCC at Yonsei University Health System, Korea. Of those, we excluded 99 patients who had total necrosis due to previous treatment. Among the remaining 625 patients, we compared the homogeneous moderately differentiated group (HG2, n=241), mixed histologic grades with the worst component as poorly differentiated group (M2, n=142), and homogeneous poorly differentiated group (HG3, n=156). The clinicopathologic features, disease-free survival (DFS) and overall survival (OS) in each group were analyzed. RESULTS: The DFS and OS were significantly lower in M2 than in HG2 (P=0·004 and 0·025, respectively) whereas those of M2 were not significantly different from HG3. There were no significant differences in the clinicopathologic features of each group except that microvascular invasion was more frequently observed in M2 than in HG2. On multivariate analysis, being in the worst histologic group (M2 and HG3) was an independent poor prognostic factor for DFS and OS (P=0·028 and <0·001, respectively). CONCLUSIONS: In patients with advanced histologic grade, the worst histologic grade may determine the prognosis after curative resection of HCC.
Journal of Gastroenterology and Hepatology 03/2013; · 2.87 Impact Factor
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Mi Sung Park,
Beom Kyung Kim,
Kyung Sik Kim,
Ja Kyung Kim,
Seung Up Kim, Jun Yong Park,
Do Young Kim,
Oidov Baartarkhuu,
Kwang Hyub Han,
Chae Yoon Chon,
Sang Hoon Ahn
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ABSTRACT: The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment.
Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks.
The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log10 IU/mL, week 96: -4.27 log10 IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P=0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm.
There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available.
Clinical and molecular hepatology. 03/2013; 19(1):29-35.
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ABSTRACT: BACKGROUND: The enhanced liver fibrosis (ELF) value is a non-invasive serum marker used for assessing liver fibrosis in chronic liver disease. To use the ELF value for the purpose of screening the general population and selecting subpopulations at high risk, it is important to know the normal range of ELF values as a prerequisite. AIMS: We aimed to define the normal range of ELF values by recruiting apparently healthy subjects and investigating factors influencing ELF values in subjects with minimal fibrotic burden. METHODS: ELF values were determined in a cohort of healthy subjects who underwent a health check-up and in healthy living liver donors who were screened for transplantation. None of subjects suffered from chronic heart disease, diabetes mellitus, metabolic syndrome, hepatitis B, hepatitis C, or human immunodeficiency virus infection, systemic autoimmune disease or liver dysfunction. RESULTS: Among 183 subjects analyzed, the normal ELF 5th through 95th percentile range was 5.95-8.73. Body mass index (P = 0.014) and male gender (P = 0.015) showed significant positive correlations with ELF value, whereas age did not. In multivariate linear regression analysis, platelet count was identified as the only independent factor influencing the ELF value (β=-0.006, P = 0.016). When considering the difference in ELF values between genders, the normal range of men was defined to be 6.72-8.93, this was slightly higher than that of women, 5.69-8.67. CONCLUSIONS: We identified the normal range of ELF values and found that it can be significantly influenced by platelet count even in the healthy population.
Liver international: official journal of the International Association for the Study of the Liver 02/2013; · 3.82 Impact Factor
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ABSTRACT: AIM: To clarify the role of surgical resection for multiple hepatocellular carcinomas (HCCs) compared to transarterial chemoembolization (TACE) and liver transplantation (LT).METHODS: Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008, 160 patients who met the following criteria were retrospectively enrolled: (1) two or three radiologically diagnosed HCCs; (2) no radiologic vascular invasion; (3) Child-Pugh class A; (4) main tumor smaller than 5 cm in diameter; and (5) platelet count greater than 50 000/mm(3). Long-term outcomes were compared among the following three treatment modalities: surgical resection or combined radiofrequency ablation (RFA) (n = 36), TACE (n = 107), and LT (n = 17). The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test. To identify the patients who gained a survival benefit from surgical resection, we also investigated prognostic factors for survival following surgical resection. Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model.RESULTS: The overall survival (OS) rate was significantly higher in the surgical resection group than in the TACE group (48.1% vs 28.9% at 5 years, P < 0.005). LT had the best OS rate, which was better than that of the surgical resection group, although the difference was not statistically significant (80.2% vs 48.1% at 5 years, P = 0.447). The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group (88.2% vs 11.2% at 5 years, P < 0.001). Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6% (20/36) in the resection group and 93.5% (100/107) in the TACE group. There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients, multi-site resection was performed in 5 patients, and combined resection with RFA was performed in 8 patients. In the TACE group, only 34 patients (31.8%) were recorded as having complete remission after primary TACE. Seventy-two patients (67.3%) were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection, the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis (80.8% vs 25.5% 5-year OS rate, P = 0.006; 22.2% vs 0% 5-year disease-free survival rate, P = 0.048). Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE (25.5% vs 24.7% 5-year OS rate, P = 0.225). Twenty-nine of the 36 patients who underwent surgical resection experienced recurrence. Of the patients with cirrhosis, 80% (16/20) were within the Milan criteria at the time of recurrence after resection.CONCLUSION: Among patients with two or three HCCs, no radiologic vascular invasion, and tumor diameters ≤ 5 cm, surgical resection is recommended only in those without cirrhosis.
World Journal of Gastroenterology 01/2013; 19(3):366-374. · 2.47 Impact Factor
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ABSTRACT: GOALS:: To compare hepatocellular carcinoma (HCC) stage, treatment modality, and survival between groups submitted to different surveillance interval. BACKGROUND:: It is not clear if surveillance interval affects patient survival with HCC. STUDY:: Clinical data from 10,307 patients at risk for HCC were prospectively collected from 1990 to 2005. The characteristics of cancer and 5-year survival in patients diagnosed as HCC during follow-up were compared between surveillance interval of <6 months and beyond 6 months. RESULTS:: A total of 400 patients were diagnosed with HCC, with a mean tumor size of 3.5 cm and an annual detection rate of 2.4%. The tumor sizes detected in patients with surveillance interval ≤6 months were significantly smaller than those detected in patients with interval of >6 months (n=219; 3.0±1.7 cm vs. n=181; 4.0±2.6 cm, P<0.001). The survival benefit in patients with surveillance interval of ≤6 months was significant compared with those with interval of >6 months even after considering lead time with assumed tumor doubling time of 60 days. The 5-year survival of HCC patients surveyed between 2000 and 2004 was significantly higher compared with those surveyed between 1990 and 1994 or between 1995 and 1999 (41% vs. 17% and 19%, respectively, P<0.0001). Using a Cox regression model, Child-Pugh class, Japanese tumor-node-metastasis stage, and α-fetoprotein levels were independently associated with patient survival. CONCLUSIONS:: Our data show that surveillance ≤6 months might be associated with early detection of HCC and improved survival in a hepatitis B endemic area.
Journal of clinical gastroenterology 01/2013; · 2.21 Impact Factor
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ABSTRACT: To investigate the diagnostic performance of acoustic radiation force impulse (ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.
This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011. Among them, 12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location (deeper than 8 cm) (n = 7) or poor compliance to hold their breath as required (n = 5). Finally, 50 patients with valid ARFI measurements were enrolled. If a patient had multiple liver masses, only one mass of interest was chosen. The masses were diagnosed by histological examination or clinical diagnostic criteria. During ultrasonographic evaluation, stiffness, expressed as velocity, was checked 10 times per focal liver mass and the surrounding liver parenchyma.
After further excluding three masses that were non-diagnostic on biopsy, a total of 47 focal mass lesions were tested, including 39 (83.0%) malignant masses [24 hepatocellular carcinomas (HCC), seven cholangiocellular carcinomas (CCC), and eight liver metastases] and eight (17.0%) benign masses (five hemangiomas and three focal nodular hyperplasias, FNH). Thirty-seven (74.0%) masses were confirmed by histological examination. The mean velocity was 2.48 m/s in HCCs, 1.65 m/s in CCCs, 2.35 m/s in metastases, 1.83 m/s in hemangiomas, and 0.97 m/s in FNHs. Although considerable overlap was still noted between malignant and benign masses, significant differences in ARFI values were observed between malignant and benign masses (mean 2.31 m/s vs 1.51 m/s, P = 0.047), as well as between HCCs and benign masses (mean 2.48 m/s vs 1.51 m/s, P = 0.006). The areas under the receiver operating characteristics curves (AUROC) for discriminating the malignant masses from benign masses was 0.724 (95%CI, 0.566-0.883, P = 0.048), and the AUROC for discriminating HCCs from benign masses was 0.813 (95%CI, 0.649-0.976, P = 0.008). To maximize the sum of sensitivity and specificity, an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses. Furthermore, the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s. The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved (AUROC = 0.853; 95%CI, 0.745-0.960; P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948; 95%CI, 0.896-0.992, P < 0.001 in HCCs vs benign masses).
ARFI elastography provides additional information for the differential diagnosis of liver masses. However, our results should be interpreted in clinical context, because considerable overlap in ARFI values existed among liver masses.
World Journal of Gastroenterology 01/2013; 19(2):219-26. · 2.47 Impact Factor
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ABSTRACT: Background/Aims: Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have been used as diagnostic tools for hepatocellular carcinoma (HCC). However, prediction of outcome using AFP and DCP has not been elucidated. We investigated the clinical role of AFP and DCP as predictors of treatment outcome in patients with HCC undergoing trans-arterial chemoembolization (TACE). METHODS: Between January 2003 and December 2005, we enrolled 115 treatment-naive patients who received TACE as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 50% from the baseline level 1 month after TACE. Patients with AFP < 20 ng/mL or DCP < 20 mAU/mL were excluded. RESULTS: The median age was 59 years and the male gender predominated (n = 81, 70.4%). AFP and DCP response was identified in 91 (79.1%) and 77 (66.9%) patients after TACE. Although progression-free survival (PFS) did not differ according to AFP response (P = 0.150), AFP responders showed significantly better overall survival (OS) than non-responders (34.9 vs. 13.2 months; P = 0.002). In contrast, DCP response did not influence either PFS or OS (all P > 0.05). Multivariate analyses showed that gamma-glutamyltranspeptidase and baseline AFP were predictors of PFS (all P < 0.05) and that male gender, the presence of liver cirrhosis, baseline DCP, number of measurable tumors and AFP response were independent predictors of OS (all P < 0.05). CONCLUSIONS: AFP response and higher baseline DCP level are significant predictors of OS in treatment-naive patients with HCC receiving TACE who showed pretreatment elevation of both AFP and DCP.
BMC Cancer 01/2013; 13(1):5. · 3.01 Impact Factor
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Sang Hoon Han,
Seung Up Kim,
Chang Oh Kim,
Su Jin Jeong, Jun Yong Park,
Jun Yong Choi,
Do Young Kim,
Sang Hoon Ahn,
Young Goo Song,
Kwang-Hyub Han,
June Myung Kim
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ABSTRACT: Liver stiffness measurement (LSM) using transient elastography (Fibroscan®) can identify individuals with potential underlying liver disease. We evaluated the prevalence of abnormal LSM values as assessed using LSM and its predictors in HIV-infected asymptomatic patients receiving combined antiretroviral treatment (cART) without HBV/HCV coinfection.
We prospectively recruited 93 patients who had consistently been undergoing cART for more than 12 months at Severance Hospital in Seoul, Republic of Korea, from June to December 2010. LSM values >5.3 kPa were defined as abnormal.
Thirty-nine (41.9%) had abnormal LSM values. On multivariate correlation analysis, the cumulative duration of boosted and unboosted protease inhibitors (PIs) were the independent factors which showed a negative and positive correlation to LSM values, respectively (β = -0.234, P = 0.023 and β = 0.430, P<0.001). In multivariate logistic regression analysis, the cumulative exposure duration of boosted-PIs and γ-glutamyltranspeptidase levels were selected as the independent predictors which showed a negative and positive correlation with abnormal LSM values, respectively (odds ratio [OR], 0.941; 95% confidence interval [CI], 0.889-0.997; P = 0.039 and OR, 1.032; 95% CI, 1.004-1.060; P = 0.023).
The high percentage of HIV-infected asymptomatic patients receiving cART without HBV/HCV coinfection had abnormal LSM values. The cumulative exposure duration of boosted-PIs and γ-GT level were independent predictors which showed a negative and positive correlation with abnormal LSM values, respectively.
PLoS ONE 01/2013; 8(1):e52720. · 4.09 Impact Factor
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ABSTRACT: Purpose: Refractory ascites (RA) is closely related to a high morbidity and mortality. In this study, we investigated predictors of RA development in patients with hepatitis B virus (HBV)-related cirrhosis who were hospitalized to control ascitic decompensation, and determined predictors for survival in patients who experienced RA. Materials and Methods: We analyzed 199 consecutive patients with HBV-related cirrhosis who were hospitalized to control ascitic decompensation between January 1996 and December 2008. Results: Multivariate analyses showed that only serum potassium at admission predicted RA development independently [p=0.013; hazard ratio (HR), 2.800; 95% confidence interval (CI), 1.166-6.722]. During the follow-up period, 16 (8.0%) patients experienced RA within 4.2 (range, 1.0-39.2) months after admission for controlling ascitic decompensation, and they survived a median of 8.7 (range, 3.9-51.3) months. Child-Pugh class and RA type were identified as independent prognostic factors affecting the survival in patients with RA (p=0.045; HR, 8.079; 95% CI, 1.231-67.984 and p=0.013; HR, 14.510; 95% CI, 1.771-118.874, respectively). Conclusion: Serum potassium was an independent predictor of RA development in patients with HBV-related cirrhosis who were hospitalized to control ascitic decompensation. After RA development, Child-Pugh class and RA type were independent predictors for survival.
Yonsei medical journal 01/2013; 54(1):145-53. · 0.77 Impact Factor
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Hwa Pyoung Kang,
Hosun Lee,
Tak Geun Oh,
Kyong Joo Lee,
Soo Jung Park,
Moon Jae Chung,
Seung Up Kim,
Hyuk Lee,
Jun Chul Park,
Sung Pil Hong, Jun Yong Park,
Jeong Youp Park,
Seungmin Bang,
Do Young Kim,
Jae Hee Cheon,
Sang Hoon Ahn,
Tae Il Kim,
Seung Woo Park,
Si Young Song
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ABSTRACT: As an adjunct to cancer treatment, the use of health functional foods (HFFs) seems to be increasing. However, little is known for the use of HFFs among cancer patients in Korea. The aims of this study were to investigate the exposure rate of HFF use among gastrointestinal (GI) cancer patients and to examine the relationship of socio-demographic and disease-related characteristics with the use of HFFs. A total of 126 patients diagnosed with GI cancer participated in the study. A cross-sectional survey was conducted using a questionnaire. Over a half of all the patients surveyed (n = 67; 53.2%) used HFFs. Patients who were younger, had higher income, or longer duration of disease showed a trend to use HFFs more frequently, even though the tendency was not statistically significant. The most commonly used HFF was vitamin complex (n = 20; 16%), followed by red ginseng (n = 15; 12%), and sweet wormwood (Artemisia annua) (n = 11; 8.8%). About 26% of all responders expressed concerns for using HFFs. The primary concern was 'going against physician's recommendations' (36.8%). About 63% of respondents expressed a desire to consult with their physicians and follow their recommendations. More basic scientific data and educational materials regarding HFFs are required for both health-care professionals and cancer patients. A larger sample and size-controlled groups representing each cancer type will continue to be recruited for participation in this survey.
Clinical nutrition research. 01/2013; 2(1):19-25.
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ABSTRACT: Prescribers, payors and healthcare decision-makers are increasingly examining the value of treatments. This study aims at analyzing economic value of chronic hepatitis B (CHB) treatment options, which are available in Korea.
CHB infection was simulated using a health-state transition model with disease states defined as mild disease (Ishak F0/F1), fibrosis (F2/F3/F4), advanced fibrosis/cirrhosis (>F4), and complicated disease states (decompensated cirrhosis, hepatocellular carcinoma, liver transplant and death) based on available natural history data. The value of treatment-specific attributes on disease progression/regression was estimated based on published data in terms of events and costs avoided. 5-year treatment duration was assumed except for treatment initiation. Primary model output is the estimated cost savings of entecavir per patient per day of treatment versus the comparator in question for a given CHB patient.
The simulation of treating with entecavir versus no treatment predicted improved clinical outcomes for entecavir-treatment patients. In the long term, these clinical benefits translate into cost savings of $3.10 per day of treatment. In naive patient treatment, daily cost savings of using entecavir versus lamivudine or telbivudine was estimated at $2.89 and $1.72, respectively. In the case of suboptimal responders who pre-treated with lamivudine, daily cost saving for patients switching to entecavir was $1.38 per day of treatment compared to patients maintaining on lamivudine.
Entecavir exhibits characteristics of a favourable CHB treatment, which directly translates into economic and therapeutic value as opposed to either no treatment or alternative strategies.
PLoS ONE 01/2013; 8(3):e57900. · 4.09 Impact Factor
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ABSTRACT: Variceal hemorrhage is a common and devastating complication of portal hypertension and is a leading cause of death in patients with cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in improved mortality and morbidity rates. Regarding the primary prevention of variceal hemorrhaging, nonselective β -blockers should be the first-line therapy in all patients with medium to large varices and in patients with small varices associated with high-risk features such as red wale marks and/or advanced cirrhosis. EVL should be offered in cases of intolerance or side effects to β -blockers, or for patients at high-risk for variceal bleeding who have medium or large varices with red wale marks or advanced liver cirrhosis. In acute bleeding, vasoactive agents should be initiated along with antibiotics followed by EVL or endoscopic sclerotherapy (if EVL is technically difficult) within the first 12 hours of presentation. Where available, terlipressin is the preferred agent because of its safety profile and it represents the only drug with a proven efficacy in improving survival. All patients surviving an episode of bleeding should undergo further prophylaxis to prevent rebleeding with EVL and nonselective β -blockers.
International journal of hepatology. 01/2013; 2013:434609.
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ABSTRACT: The FibroTest (FT) demonstrated excellent diagnostic performance in the prediction of liver fibrosis in patients with chronic hepatitis B (CHB). Here, we aimed to identify predictors of discordance between FT and liver biopsy (LB) in Asian patients with CHB.
Consecutive patients with CHB who underwent both LB and FT on the same day between 2007 and 2010 were recruited from three medical institutes. Laboratory evaluations including specific parameters for calculating FT score, such as α2-macroglobulin, apolipoprotein A1, haptoglobin, γ-glutamyl transpeptidase, and total bilirubin levels, were obtained. The Batts and Ludwig scoring system was used for histological analysis.
A total of 330 patients (200 male and 130 female) were analyzed. Discordances of at least two fibrosis stages between FT and LB were observed in 30 (9.1%) patients; using FT, fibrosis was underestimated in 25 patients and overestimated in 5 patients with reference to LB. Patients with discordance had a higher proportion of F3-4 (P<0.001) and F4 (P = 0.012) compared with those with nondiscordance. The discordance rate was significantly higher in those with F3-4 than those with F1-2 (15.4% vs. 3.0%, P<0.001). Multivariate analysis demonstrated F3-4 at LB as the only independent factor for discordance (P<0.001; odds ratio 5.95). After adjusting fibrosis stages, neither necroinflammatory activity on histology nor serum ALT level influenced FT values independently.
Advanced fibrosis stage (F3-4) is the sole factor of discordance between FT and LB in Asian patients with CHB.
PLoS ONE 01/2013; 8(2):e55759. · 4.09 Impact Factor
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ABSTRACT: Purposes:To date, most studies regarding optimal number of target lesions for enhancement criteria for hepatocellular carcinoma (HCC) have focused on cross-sectional analyses of concordance. We investigated optimal number of target lesions for EASL and mRECIST guidelines in predicting overall survival (OS). EXPERIMENTAL DESIGN: We analyzed 254 consecutive treatment-naive HCC patients having at least two measurable target lesions undergoing transarterial chemoembolization. Kappa-values for intermethod agreement of treatment responses were calculated for comparisons between use of maximum of one, two, three, four, or five targets versus use of all target lesions. Prognostic values of radiological assessments according to number of target lesions for predicting OS were expressed as C-index. RESULTS: By EASL and mRECIST guidelines, kappa-values between responses assessing the longest two, three, four, or five targets and assessing all targets were 0.924, 0.977, 1.000, or 1.000 and 0.907, 0.959, 1.000, or 1.000 respectively, whereas those between responses assessing only one target and assessing all target lesions were 0.723 and 0.666, respectively. C-index when measuring the longest one, two, three, four, five, and all targets was similar, ranging from 0.739 to 0.749 for EASL criteria and from 0.750 to 0.759 for mRECIST. From Cox regression analyses, radiological response from each calculation method demonstrated independently significant effects on OS for both guidelines, regardless of number of target lesions. CONCLUSIONS: Prognostic values for predicting OS were similar regardless of number of target lesions. Assessing the two largest targets rather than only one index lesion is recommended considering high concordances from cross-sectional analyses.
Clinical Cancer Research 12/2012; · 7.74 Impact Factor
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ABSTRACT: PURPOSE: Although sorafenib has been approved for treating advanced hepatocellular carcinoma (HCC), its high cost, frequent adverse events, and unsatisfactory efficacy remain unresolved. We evaluated the efficacy and safety of the combination treatment of localized concurrent chemoradiation therapy (CCRT) for locally advanced HCC with portal vein thrombosis (PVT) and transarterial chemoembolization (TACE) for intrahepatic metastasis. METHODS: Between January 2006 and June 2011, 30 patients with HCC with portal vein invasion and intrahepatic metastasis were enrolled. After TACE for intrahepatic metastasis, localized CCRT (45 Gy over 5 weeks with conventional fractionation and hepatic artery infusional chemotherapy using 5-fluorouracil as a radiosensitizer, administered during the first and fifth weeks of radiotherapy) was used to treat main HCC with PVT. The modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate tumor response. RESULTS: The median age of the patients (26 men, 4 women) was 51 years. Objective response rates were 30.0 % (9/30) and 32.1 % (9/28) in the intention-to-treat and per protocol analyses, respectively. The median progression-free survival (PFS) and overall survival (OS) were 4.5 and 9.8 months, respectively. Baseline α-fetoprotein (AFP) correlated significantly with PFS (P = 0.008), whereas baseline AFP, completion of the protocol, and overall radiological response influenced OS significantly (all P < 0.05). All adverse events were predictable and manageable with conservative care. CONCLUSIONS: Combination treatment of localized CCRT and TACE was effective and tolerable in patients with locally advanced HCC with PVT and intrahepatic metastasis. This protocol may be an alternative option when sorafenib cannot be prescribed.
Cancer Chemotherapy and Pharmacology 10/2012; · 2.83 Impact Factor
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ABSTRACT: The relationship between cytokines and responses to peginterferon alpha-2a treatment in chronic hepatitis B patients has not yet been fully elucidated. We analyzed the serum levels of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-gamma, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP1) and epidermal growth factor during the treatment with peginterferon alpha-2a.
Ninety-three serum samples from 20 chronic hepatitis B patients were collected before, during and after 48 weeks of peginterferon therapy and were assayed for 12 cytokines. The patients were categorized as either virologic responders (VRs) or non-responders (NRs) according to their HBV DNA levels taken at 6th month during treatment. The Evidence Investigator (Randox, Antrim, UK), a protein chip analyzer, was used to quantify cytokines.
Among the 12 cytokines, the levels of MCP1 were increased and the levels of IL-4 were decreased during the treatment in VRs. However these cytokines were not significantly changed in NRs in the treatment phases. Area under the receiver operating characteristic curve (AUROC) value of HBV DNA measured before the treatment was 0.81 in predicting VRs, and that of the baseline MCP1 was 0.76. IL-6 levels at 3rd and 6th months during the treatment also showed AUROC values 0.85 and 0.78 respectively in predicting sustained VRs.
Serum cytokine levels reflect the pathological differences of individual treatment phases and could also be useful in monitoring responses to peginterferon treatment in chronic hepatitis B patients.
Hepatobiliary & pancreatic diseases international: HBPD INT 10/2012; 11(5):499-506. · 1.08 Impact Factor
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ABSTRACT: BACKGROUNDS: European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumours (mRECIST) guidelines, which measure changes in arterialised hepatocellular carcinoma (HCC), differ in terms of number of target lesions (all versus ⩽2) and calculation method (bidimensional versus unidimensional). We compared prognostic values of mRECIST for predicting overall survival (OS) with reference to EASL criteria in treatment-naïve HCC undergoing trans-arterial chemoembolisation (TACE). METHODS: The ability to predict OS during longitudinal follow-up was expressed as C-index, and a sample size of 292 patients was required to validate its equivalence between each criteria. Treatment responses were assessed using both guidelines 4weeks after the first TACE, using dynamic computed tomography or magnetic resonance imaging. Kaplan-Meier and Cox regression analyses were used to explore differences in OS between responders (complete or partial) and non-responders (stable or progressive disease), defined by each method. RESULTS: C-index for EASL and mRECIST guidelines was 0.753 and 0.759, respectively, demonstrating equivalence between two methods. Differences in median OS between responders and non-responders were statistically significant for both EASL (30.1 versus 18.7months, p<0.001) and mRECIST (33.8 versus 17.1months, p<0.001) guidelines. In addition to radiological response, α-fetoprotein (p<0.001), tumour number (p<0.001) and tumour size (p=0.048) were significant predictors of OS. In multivariate analysis, radiological criteria, tumour number and α-fetoprotein were identified as independent predictors (all p<0.05). CONCLUSION: mRECIST, a simpler method, provided prognostic values for predicting OS equivalent to EASL criteria in patients with HCC undergoing TACE as an initial treatment modality.
European journal of cancer (Oxford, England: 1990) 09/2012; · 4.12 Impact Factor
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ABSTRACT: Background/Aim: Periodic endoscopy for esophageal varices (EVs) and prophylactic treatment of high-risk EVs, i.e. medium/large EVs, small EVs with the red-color sign or decompensation, are recommended in cirrhotic patients. We assessed the cumulative risks for future EV bleeding using the following simple P2/MS index: (platelet count)(2)/[monocyte fraction (%) × segmented neutrophil fraction (%)]. Methods: We enrolled 475 consecutive B-viral cirrhosis patients for 4 years, none of whom experienced EV bleeding. All underwent laboratory work-ups, endoscopy and ultrasonography. Those with EV bleeding took a nonselective β-blocker as prophylaxis. The major endpoint was the first occurrence of EV bleeding, analyzed using the Kaplan-Meier and Cox regression methods. Results: Among patients with EV bleeding (n = 131), 25 experienced their first EV bleeding during follow-up. To differentiate the risk for EV bleeding, we divided them into two subgroups according to their P2/MS value (subgroup 1: P2/MS ≥9 and subgroup 2: P2/MS <9). The risk was significantly higher in subgroup 2 (p = 0.029). From multivariate analysis, a lower P2/MS (p = 0.040) remained a significant predictor for EV bleeding along with large varix size (p = 0.015), red-color sign (p = 0.041) and Child-Pugh classification B/C (p = 0.001). In subgroup 1, the risk for EV bleeding was similar to that of patients with low-risk EVs (p = 0.164). Conclusions: The P2/MS is a reliable predictor for the risk of EV bleeding among patients with EV bleeding. According to risk stratification, different prophylactic treatments should be considered for the subgroup with a P2/MS <9.
Digestion 09/2012; 86(3):264-272. · 2.05 Impact Factor
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Jeong Heo, Jun Yong Park,
Heon Ju Lee,
Won Young Tak,
Soon Ho Um,
Do Young Kim,
Ki Tae Yoon,
Soo Young Park,
Yeon Seok Seo,
Kwang-Hyub Han,
Mong Cho,
Sang Hoon Ahn
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ABSTRACT: BACKGROUNDS: Growing numbers of chronic hepatitis B (CHB) patients in the Asia Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96 week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virologic response to lamivudine. METHODS: A total of 72 HBeAg-positive patients, with serum HBV DNA ≥60 IU/mL after at least 6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. RESULTS: Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained, and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log(10) IU/mL for lamivudine-maintained and entecavir-switch patients, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time-points (67.6% versus 11.4% at Week 96 [P<0.001]). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by Week 4, maintained through Week 96. Entecavir-switch patients with baseline HBV DNA <5 log(10) IU/mL were more likely to achieve a virologic response at Week 96. Six entecavir-switch (17.6%) and two lamivudine-maintained (5.7%) patients achieved HBeAg loss, and three entecavir (8.8%) and one lamivudine (2.9%) patients achieved HBeAg seroconversion. Genotypic resistance to assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks. CONCLUSIONS: Switching to entecavir in patients with a partial virologic response to lamivudine resulted in increased virologic efficacy and lower rates of antiviral resistance than maintaining lamivudine.
Antiviral therapy 08/2012; · 3.16 Impact Factor
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ABSTRACT: The number of HIV-infected individuals susceptible to Hepatitis A virus (HAV) infection is increasing in Korea; however, it has proven difficult to devise a vaccination policy therefore because limited seroepidemiologic data exists for them. Accordingly, anti-HAV IgG was measured in 188 HIV-infected adults between July 2008 and July 2010. The nadir CD4+ T lymphocyte counts were not different between the HAV-positive and -negative groups (197 ± 138 vs 202 ± 129, P = 0.821). The only factor independently associated with seropositive status was age under 40 yr old (OR 0.017, P < 0.001). Our findings suggest that HAV vaccination in HIV-infected adults should be targeted at persons under the age of 40 yr.
Journal of Korean medical science 08/2012; 27(8):969-71. · 0.84 Impact Factor
