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      • Prevalence of Aflatoxin Induced p53 Mutation at Codon 249 (R249s) in Hepatocellular Carcinoma Patients with and without Hepatitis B Surface Antigen (HBsAg)

        Chittmittrapap, Salyavit,Chieochansin, Thaweesak,Chaiteerakij, Roongruedee,Treeprasertsuk, Sombat,Klaikaew, Naruemon,Tangkijvanich, Pisit,Komolmit, Piyawat,Poovorawan, Yong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

        Background: A missense mutation in exon 7 (R249S) of the p53 tumor suppressor gene is characteristic of aflatoxin B1 (AFB1) exposure. AFB1 is believed to have a synergistic effect on hepatitis virus B (HBV) carcinogenesis. However, results of studies comparing R249S prevalence among patients are conflicting. The aim of this study was to determine the prevalence of the R249S mutation in hepatocellular carcinoma (HCC) patients with or without positive HBsAg. Materials and Methods: Paraffin embedded liver tissues were obtained from 124 HCC patients who underwent liver resection and liver biopsy in King Chulalongkorn Memorial Hospital. Restriction fragment length polymorphism (RFLP) was utilized to detect the R249S mutation. Positive results were confirmed by direct sequencing. Results: Sixty four (52%) patients were positive for HBsAg and 18 (15%) were anti-HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were confirmed to be R249S positive by Sanger sequencing (AGG to AGT). Out of these 10, six were HBsAg positive, and out of the remaining 4, two were anti-HCV positive. The R249S prevalence among HCC patients with positive HBsAg was 9.4% compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation were younger ($55{\pm}10$ vs $60{\pm}13$ year-old) and tended to have a more advanced Edmonson-Steiner grade of HCC, although differences did not reach statistical significance. Conclusions: Our study shows moderate prevalence of aflatoxin B1-related p53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status was not associated with R249S prevalence.

      • KCI등재

        Liver Fluke-Associated Biliary Tract Cancer

        ( Piyapan Prueksapanich ),( Panida Piyachaturawat ),( Prapimphan Aumpansub ),( Wiriyaporn Ridtitid ),( Roongruedee Chaiteerakij ),( Rungsun Rerknimitr ) 대한간학회 2018 Gut and Liver Vol.12 No.3

        Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The “liver fluke-cholangiocarcinoma” carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke’s antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas. (Gut Liver 2018;12:236- 245)

      • Model to estimate survival in ambulatory patients with hepatocellular carcinoma

        Yang, Ju Dong,Kim, W. Ray,Park, Kyung Woo,Chaiteerakij, Roongruedee,Kim, Bohyun,Sanderson, Schuyler O.,Larson, Joseph J.,Pedersen, Rachel A.,Therneau, Terry M.,Gores, Gregory J.,Roberts, Lewis R.,Park Wiley Subscription Services, Inc., A Wiley Company 2012 Hepatology Vol.56 No.2

        <P><B>Abstract</B></P><P>Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha‐fetoprotein. In cross‐validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)‐statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification. <I>Conclusion</I>: A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification. (H<SMALL>EPATOLOGY</SMALL> 2012)</P>

      • KCI등재

        Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis

        Decharatanachart Pakanat,Pan-ngum Wirichada,Peeraphatdit Thoetchai,Tanpowpong Natthaporn,Tangkijvanich Pisit,Treeprasertsuk Sombat,Treeprasertsuk Sombat,Chaiteerakij Roongruedee 거트앤리버 소화기연관학회협의회 2024 Gut and Liver Vol.18 No.1

        Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.

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