The correlation of hepatitis B virus pre-S mutation with mitochondrial D-loop mutations and common deletions in hepatocellular carcinoma.

BACKGROUND/AIMS: We investigated the correlation of HBV pre-S mutation with the sites and frequencies of mtDNA mutations in HCC patients. METHODOLOGY: Twenty-seven HBV-related HCC patients and 8 control patients were included. HBV DNA was extracted from sera and the HBV S coding region was analyzed. Direct sequencing of the mtDNA D-loop was performed in paired HCC and adjacent non-neoplastic liver tissues. The common 4977 bp deletion of miDNA was examined by PCR. RESULTS: Study subjects were categorized into three groups: the pre-S mutant HBV-infected HCC patients (group 1), wild-type HBV-infected HCC patients (group 2) and HBV non-infected patients (group 3). The frequency of mtDNA D-loop mutations in non-neoplastic tissue was higher in group 1/2 than in group 3; however, there was no significant difference between group 1 and 2. The frequency of mtDNA D-loop mutations showed no significant difference between HCC and nonneoplastic tissues. The prevalence of the common 4977 bp deletion was lower in HCC compared to non-neoplastic tissues, however, there was no difference according to the pre-S mutation. CONCLUSION: The present study does not support a pathophysiological role for the HBV pre-S mutation, related to mtDNA D-loop mutation or alteration of the common 4977 bp deletion, in hepatocarcinogenesis.

The correlation of hepatitis B virus pre-S mutation with cellular oxidative DNA damage in hepatocellular carcinoma.

BACKGROUND/AIMS: Recent research has proposed a role for HBV pre-S mutation in the development of HCC. Although the mechanism is not clear, pre-S mutant-induced endoplasmic reticulum (ER) stress and oxidative DNA damage may participate in this process. Therefore, we investigated the correlation of HBV pre-S mutation with ER stress and cellular oxidative DNA damage in HBV-related HCC patients. METHODOLOGY: Thirty HBV-related HCC patients and 8 control patients were included. HBV DNA was extracted from sera and the HBV S coding region was analyzed by PCR and sequencing. Immunohistochemical staining for 8-oxoG and OGG1 were performed in HCC and non-neoplastic tissues. RESULTS: Study subjects were categorized into three groups: the pre-S mutant HBV-infected HCC patients (group 1, n=20), wild-type HBV-infected HCC patients (group 2, n=10) and HBV non-infected patients (group 3, n=8). The expression level of 8-oxoG and OGG1 in non-neoplastic tissue was higher in group 1/2 than in group 3; however, there was no significant difference between group 1 and 2. There was no significant difference in 8-oxoG/OGG1 expressions between HCC and non-neoplastic tissues. CONCLUSIONS: The present study did not support a pathophysiologic role for HBV pre-S mutation, related to ER stress and oxidative DNA damage, in hepatocarcinogenesis.

Diagnosis and treatment of metachronous gastric cancers after surgical treatment for esophageal squamous cell carcinoma.

BACKGROUND/AIMS: With the improvement of the outcome after esophagectomy for esophageal cancer, patients with metachronous gastric cancer (MGC) in the reconstructed thoracic stomach have been observed in clinical practice. This study is a report of experiences with MGC with an emphasis on clinical pictures and treatment results. METHODOLOGY: Medical records were reviewed of 728 patients who underwent surgery for esophageal cancer at Samsung Medical Center between 1994 and 2004. MGC was defined as follows; (1) diagnosed more than 6 months after esophagectomy, (2) squamous cell carcinoma in histology of the surgically resected esophagus, (3) adenocarcinoma in histology of the stomach biopsy or surgical specimen. The clinicopathologic characteristics of MGC were evaluated. RESULTS: Eight patients (1.1%) of 728 patients were diagnosed with MGC. All patients were male and had a history of active smoking and drinking. The median age at the time of diagnosis of MGC was 67.8 years old (range: 62-76). Three patients (37.5%) were asymptomatic. Two patients (25%) complained of epigastric pain and 3 patients (37.5%) complained of obstructive symptoms including regurgitation, aspiration, dysphagia, and vomiting. The median interval between diagnosis of MGC and esophagectomy was 37 months (range: 8-85). Three MGCs (37.5%) were detected by endoscopic examination but not by computed tomography (CT). Three patients (37.5%) received surgery and were alive without recurrence for 12, 18 and 63 months respectively. One patient (12.5%) received radiation therapy and was alive for 69 months. Four patients (50%) received no treatment because of follow-up loss in 2 patients (25%) and death within days of MGC diagnosis in 2 patients (25%). CONCLUSIONS: Favorable outcomes can be obtained by active treatment in patients with MGC after esophagectomy. Regular endoscopic follow-up is important for early detection and more effective treatment of MGC, especially in areas where the incidence of gastric cancer is high.

[An evaluation of web-based informations about gastroesophageal reflux diseases in Korea].

BACKGROUND/AIMS: Internet has become an important source of medical information not only for medical personnels but also for patients. The aim of this study was to evaluate the quality of internet based medical information about 'gastroesophageal reflux' or 'reflux esophagitis' in Korea. METHODS: The first 15 internet sites using the key words 'gastroesophageal reflux' or 'reflux esophagitis' were retrieved from the 7 most frequently used internet search engines. The quality of information from a total of 108 websites was evaluated using a checklist. RESULTS: Among total 108 sites related to 'gastroesophageal reflux' or 'reflux esophagitis', fifty-six sites (51.8%) were made by hospitals or clinics and 94 sites (87.0%) were made for patients. Of the 108 sites, eleven web sites (10.1%) had more than three JAMA benchmarks (authorship, references, currency, and disclosure). Higher quality sites (at least three JAMA benchmarks) were less likely to contain inaccurate information than lower quality sites (fewer than three JAMA benchmarks)-3/11 (27.2%) vs. 60/97 (61.9%) (p<0.01). Despite the fact that articles in the literature emphasized an insufficient evidence to support an association between the lifestyle, dietary behaviors, and GERD, such guidelines continue to be recommended as first-line therapy in most websites. CONCLUSIONS: Informations about gastroesophageal reflux disease were incomplete in the majority of medical web sites. These would bring about confusion to patients seeking for an information about GERD through the internet. There is a need for better sources in evidence based informations about gastroesophageal reflux diseases on the web.

[Comparative usefulness of erythrocyte sedimentation rate and C-reactive protein in assessing the severity of ulcerative colitis].

BACKGROUND/AIMS: Although erythrocyte sedimentation rate (ESR) is included as a laboratory parameter in Truelove and Witts' classification, C-reactive protein (CRP) is also used for severity assessment in ulcerative colitis (UC). Frequently, the discordance between ESR and CRP is observed in clinical practice. The aim of this study was to determine which parameter is more related with clinical activity in UC patients. METHODS: A total of 155 patients with UC were identified from January 2004 to March 2005. Their medical records were reviewed within these patients, a total of 541 assessments of disease activity were made. Correlation of clinical activity and laboratory tests were evaluated by Pearson's correlation coefficient. RESULTS: Pearson's correlation coefficients of ESR and CRP with clinical symptoms were 0.376 and 0.258, respectively. The correlation coefficient between ESR and CRP was 0.403 (p=0.000). A total of 131 (24.2%) assessments revealed discordance between ESR and CRP. When discordance occurred, the correlation coefficients with clinical symptoms were 0.338 for ESR (p=0.000) and 0.034 for CRP (p>0.01). Dividing discordant patients into high ESR/low CRP group and low ESR/high CRP group, the coefficients were 0.420 for ESR and 0.226 for CRP in high ESR/low CRP group, and 0.333 for ESR and 0.068 for CRP in low ESR/high CRP group. CONCLUSIONS: The correlation analysis indicates that ESR appears to be a more reliable laboratory parameter of disease activity than CRP in assessing the severity of UC. In particular, when the level of ESR and CRP is discordant, ESR is more useful in assessing the disease activity in UC patients.

Glycyrrhizin attenuates HMGB1-induced hepatocyte apoptosis by inhibiting the p38-dependent mitochondrial pathway.

AIM: To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin (GL), a known HMGB1 inhibitor, prevents HMGB1-induced hepatocyte apoptosis. METHODS: A human hepatocellular carcinoma cell line stably transfected with a bile acid transporter (Huh-BAT cells), were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining and the APO Percentage apoptosis assay, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. It is also tried to identify hepatocyte apoptosis affected by the HMGB1 inhibitor, GL. RESULTS: HMGB1 increased cellular apoptosis in Huh-BAT cells. HMGB1 led to increased cytochrome c release from mitochondria into the cytosol, and induced the cleavage of procaspase 3. However, it did not affect the activation of caspase 8. HMGB1-induced caspase 3 activation was significantly attenuated by the p38 inhibitor SB203580. GL significantly attenuated HMGB1-induced hepatocyte apoptosis. GL also prevented HMGB1-induced cytochrome c release and p38 activation in Huh-BAT cells. CONCLUSION: The present study demonstrated that HMGB1 promoted hepatocyte apoptosis through a p38-dependent mitochondrial pathway. In addition, GL had an anti-apoptotic effect on HMGB1-treated hepatocytes.