Both loss of heterozygosity (LOH) and replication error (RER) are considered to be phenotypes of genomic instability. To unveil the role of the genomic instability in hepatocarcinogenesis, frequencies of LOH and RER were simultaneously determined in 15 hepatocellular carcinomas (HCCs), surrounding nontumorous liver tissues (SL), and 13 liver tissues with chronic viral hepatitis void of cancer (NC) by referencing peripheral blood leukocytes (PBLs) from the corresponding donor using 18 microsatellite markers spread throughout the genome. LOH was significantly frequent in HCC compared with that in SL or NC (P ؍ .005, P ؍ .0003, respectively) and observed preferentially at particular microsatellite loci, D1S204, D2S123, D8S1106, D9S266, D16S748, and D19S601. Although the higher prevalence of RER was also significant in HCC compared with that in NC (P ؍ .03), in most cases the errors were detected at very low frequencies and random loci. Both LOH and RER tended to appear more prevalently in SL than in NC. The occurrence rate of LOH was higher in the tissues associated with hepatitis B virus (HBV) than with hepatitis C virus (HCV) infection especially in HCC (P ؍ .03). When referencing SL instead of PBLs, the prevalence of LOH and RER in HCC significantly decreased (P ؍ .02 and P ؍ .03, respectively). These results suggest that LOH is closely associated with multistep hepatocarcinogenesis especially under HBV infection, but RER is imperceptibly associated. The quantitative evaluation of the frequency of LOH by referencing PBLs may be a useful predictor for HCC development in chronic liver diseases. (HEPATOLOGY 2000;31:1246-1250.) Hepatocellular carcinoma (HCC) is one of the most common human cancers especially in areas in which hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is prevalent. 1 Although the molecular mechanisms of hepatocarcinogenesis have not been elucidated yet, a long-lasting inflammation induced by the hepatitis virus is a definite risk for neoplastic degeneration and the accumulation of genetic alterations. Thus, it is not difficult to assume that genomic instability, such as loss of heterozygosity (LOH) and replication error (RER), has already appeared in the premalignant status and increased through hepatocarcinogenesis.LOH and RER analyses have been performed in HCC as well as in other types of cancers. [2][3][4][5][6][7][8][9] In relation to RER, its prevalence in HCC was extremely low compared with that in so called RER-positive cancers such as hereditary nonpolyposis colorectal cancer. [7][8][9][10][11] It is possible that the lower incidence of RER was derived from the employment of surrounding noncancerous liver tissues (SL) as a referencing material, in which genetic alterations might have already been accumulated. The same problem might be involved in LOH analyses. Thus, it might be ideal to reevaluate the frequency of LOH and RER in chronic liver diseases using the tissues out of the liver as referencing materials.In this study, we simultaneously investigated LOH a...
BACKGROUND. Despite the recent discovery of interchromosomal telomere length variation, a role for heterogeneity in telomere maintenance has yet to be established. This study investigated the significance of telomere length variation between chromosomes with respect to the association of cancer progression and telomere length regulation. METHODS. Terminal restriction fragment (TRF) was evaluated in 20 surgically resected hepatocellular carcinoma specimens (HCC), corresponding noncancerous liver tissue specimens (NCL), and in 10 liver tissue specimens with chronic liver diseases devoid of cancer (DOC). Average TRF length (TRF-A) was defined as the point of maximum intensity. Shorter and longer TRF lengths (TRF-S and TRF-L) were defined as the length above which 90% of TRF distribution was involved. A ratio, (TRF-LϪTRF-S)/TRF-A, was defined as telomere length dispersion. RESULTS. The dispersion was significantly larger in HCC than in NCL specimens (P ϭ 0.012
Background: We previously reported the techniques and usefulness of simultaneous combined balloon-occluded retrograde transvenous obliteration (B-RTO) and partial splenic embolization (PSE), based on the hypothesis that concomitant PSE can diminish the increase in portal venous pressure after B-RTO. Objective: After experiencing more cases and performing longer-term follow-up, we re-evaluated the efficacy of simultaneous combined B-RTO and PSE for gastric fundal varices (GVs). Methods: We performed B-RTO in 36 consecutive patients treated for GVs from 2005 to 2013. Twenty-three patients underwent simultaneous combined B-RTO and PSE (Group 1) and 13 underwent B-RTO monotherapy (Group 2). The outcomes were retrospectively evaluated. Results: There were no significant differences in baseline characteristics between the two groups except that the splenic volumes were larger in Group 1 than 2. B-RTO was technically successful in 21 of 23 patients (91.3%) in Group 1 and in 12 of 13 patients (92.3%) in Group 2. In all patients with ruptured GVs (six in Group 1 and five in Group 2), complete hemostasis was obtained by B-RTO. Exacerbation of esophageal varices was significantly less frequent in Group 1 than 2 (p ¼ 0.0017). Conclusion: Concomitant PSE with B-RTO may contribute to prevention of the exacerbation of esophageal varices after B-RTO.
Rupture of gastric varices (GVs) can be fatal. Balloon-occluded retrograde transvenous obliteration (BRTO), as known as retrograde sclerotherapy, has been widely adopted for treatment of GVs because of its effectiveness, ability to cure, and utility in emergency and prophylactic treatment. Simplifying the route of blood flow from GVs to the gastrorenal shunt is important for the successful BRTO. This review outlines BRTO indications and contraindications, describes basic BRTO procedures and modifications, compares BRTO with other GVs treatments, and discusses various combination therapies. Combined BRTO and partial splenic embolization may prevent exacerbation of esophageal varices and shows promise as a treatment option.
Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.
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