Jaejun Shim

Mean platelet volume/platelet count ratio in hepatocellular carcinoma

Mean platelet volume (MPV) has been actively investigated in liver disease such as steatosis, cirrhosis and hepatitis. Recently, MPV/platelet count (PC) ratio has been proposed as a predictor of long-term mortality after myocardial infarction. As PC is known to be decreased in various liver diseases such as cirrhosis, hepatosplenomegaly and malignancy, we planned to evaluate MPV/PC ratio in patients with hepatocellular carcinoma (HCC) in this study. Mean of MPV levels showed significant difference, which were 8.69 fl (range 6.7–12.2 fl) in patients group and 8.02 fl in control group (range 6.7–11.0 fl). In receiver operating characteristic (ROC) curve analysis, the MPV/PC ratio (fl/(109/l)) presented 74.5% of sensitivity and 96.5% of specificity at the criterion > 0.0491 (area under the curve (AUC) = 0.884), while MPV alone showed 57.4% of sensitivity and 81.4% of specificity at the criterion > 8.4 fl. Further studies should evaluate underlying pathogenic mechanisms of MPV/PC ratio difference and various possibilities of this ratio as an indicator of presence of a tumor in HCC.

Epigenetic inactivation of the NORE1 gene correlates with malignant progression of colorectal tumors

BackgroundNORE1 (RASSF5) is a newly described member of the RASSF family with Ras effector function. NORE1 expression is frequently inactivated by aberrant promoter hypermethylation in many human cancers, suggesting that NORE1 might be a putative tumor suppressor. However, expression and mutation status of NORE1 and its implication in colorectal tumorigenesis has not been evaluated.MethodsExpression, mutation, and methylation status of NORE1A and NORE1B in 10 cancer cell lines and 80 primary tumors were characterized by quantitative PCR, SSCP, and bisulfite DNA sequencing analyses. Effect of NORE1A and NORE1B expression on tumor cell growth was evaluated using cell number counting, flow cytometry, and colony formation assays.ResultsExpression of NORE1A and NORE1B transcript was easily detectable in all normal colonic epithelial tissues, but substantially decreased in 7 (70%) and 4 (40%) of 10 cancer cell lines and 31 (38.8%) and 25 (31.3%) of 80 primary carcinoma tissues, respectively. Moreover, 46 (57.6%) and 38 (47.5%) of 80 matched tissue sets exhibited tumor-specific reduction of NORE1A and NORE1B, respectively. Abnormal reduction of NORE1 was more commonly observed in advanced stage and high grade tumors compared to early and low grade tumors. While somatic mutations of the gene were not identified, its expression was re-activated in all low expressor cells after treatment with the demethylating agent 5-aza-dC. Bisulfite DNA sequencing analysis of 31 CpG sites within the promoter region demonstrated that abnormal reduction of NORE1A is tightly associated with promoter CpG sites hypermethylation. Moreover, transient expression and siRNA-mediated knockdown assays revealed that both NORE1A and NORE1B decrease cellular growth and colony forming ability of tumor cells and enhance tumor cell response to apoptotic stress.ConclusionOur data indicate that epigenetic inactivation of NORE1 due to aberrant promoter hypermethylation is a frequent event in colorectal tumorigenesis and might be implicated in the malignant progression of colorectal tumors.

Close observation of gastric mucosal pattern by standard endoscopy can predict Helicobacter pylori infection status

Common endoscopic findings in stomachs with Helicobacter pylori infections include antral nodularity, thickened gastric folds, and visible submucosal vessels. These findings are suggestive but not diagnostic of H. pylori infection. Magnifying endoscopy can reveal more precisely the abnormal mucosal patterns in an H. pylori‐infected stomach; however, it requires more training, expertise, and time. We aimed to establish a new classification for predicting H. pylori‐infected stomachs by non‐magnifying standard endoscopy alone.

The Risk of Tuberculosis in Korean Patients with Inflammatory Bowel Disease Receiving Tumor Necrosis Factor-α Blockers

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-α blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-α blocker naïve and 160 TNF-α blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-α blockers compared to TNF-α-blocker-naïve patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-α blocker users, and 0.45 for TNF-α-blocker-naïve patients. The adjusted risk ratio of TB in IBD patients receiving TNF-α blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-α blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-α blockers. Treatment with TNF-α blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-α blocker therapy. Graphical Abstract

Oral antiviral therapy improves the diagnostic accuracy of alpha-fetoprotein levels in patients with chronic hepatitis B.

Analysis of alpha‐fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false‐positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB.

Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area

Backgound:  The presence of antibody to the hepatitis B core antigen (anti‐HBc) IgG in serum usually means a past infection of the hepatitis B virus (HBV). The clinical characteristics of patients with hepatocellular carcinoma (HCC), who have only a marker for past HBV infection, were investigated.

Anti-hepatitis B core antibody is not required for prevaccination screening in healthcare workers

Vaccination against hepatitis B virus (HBV) is recommended for health care workers (HCWs), but it is not clear whether HBV vaccination is required for HCWs who have isolated antibody to hepatitis B core antigen (anti-HBc), or whether prevaccination screening for anti-HBc is needed in HCWs. Among 1812 HCWs, subjects with isolated anti-HBc and those with no HBV markers (control) were screened. The anamnestic response (antibody to hepatitis B surface antigen over 50 mIU/mL after the first vaccine injection) was compared prospectively between the two groups. The prevalence of isolated anti-HBc was 2.3%. Their anamnestic response was lower than that of controls (27.5% vs. 46.9%, P=0.020). The subjects who had isolated anti-HBc were older and predominantly male, compared with the controls. Multivariate analysis revealed that age (odds ratio [OR], 0.67; confidence interval [CI], 0.51-0.90) and prior vaccination (OR, 3.36; CI, 2.04-5.54) were independent predictors of the anamnestic response, regardless of the anti-HBc status. Serum HBV DNA was not detected in any subject. Anti-HBs seroconversion was achieved in most of the anti-HBc-positive subjects after full vaccination, and the rate was comparable with controls (89.5% vs. 96.6%, P=0.067). Isolated anti-HBc-positive HCWs are rare and most of them respond to vaccination. Anti-HBc testing is not a prerequisite for vaccination. This serology suggests a loss of acquired anti-HBs rather than occult HBV infection. Their reduced immunity to vaccination may be related to old age.

Spontaneous rupture of a sigmoid colon gastrointestinal stromal tumor manifesting as pneumoretroperitoneum with localized peritonitis: Report of a case

Colonic gastrointestinal stromal tumors (GISTs) account for only 5%–10% of tumors arising in the digestive tract. Spontaneous rupture is a very rare manifestation of a GIST; however, we report what to our knowledge is the first documented case of pneumoretroperitoneum caused by the rupture of a GIST. A 77-year-old woman was admitted to our hospital with acute abdominal pain and hematochezia. Colonoscopy showed luminal narrowing in the sigmoid colon, but no definite mucosal defect. Computed tomography (CT) showed an air-containing heterogeneous mass, 9.7 × 9.3 cm, in the pelvic cavity and a small amount of air in the retroperitoneum. Emergency laparotomy revealed a ruptured sigmoid colonic GIST with localized peritonitis. Pathologic examination confirmed that the tumor was composed mainly of round epithelioid cells. It was immunohistochemically positive for CD34 and negative for C-kit protein. This report describes how we successfully managed pneumoretroperitoneum with localized peritonitis caused by the spontaneous rupture of an epithelioid GIST originating from the sigmoid colon.

Comparison of hemostatic forceps with soft coagulation versus argon plasma coagulation for bleeding peptic ulcer – a randomized trial

BACKGROUND AND STUDY AIMS Endoscopic high-frequency soft coagulation is used to manage visible bleeding or nonbleeding vessels during endoscopic submucosal dissection. The aim of the present study was to compare the efficacy of hemostasis by soft coagulation (using hemostatic forceps) with argon plasma coagulation (APC), in a prospective randomized trial. PATIENTS AND METHODS From January 2013 to June 2014, 276 patients were randomly assigned into two groups: epinephrine injection plus APC (the APC group); or epinephrine injection plus soft coagulation using hemostatic forceps (the HFSC group). As the primary outcome we compared recurrent bleeding rates within 30 days after initial hemostasis in a noninferiority design. RESULTS After exclusion, 75 patients in the APC group and 76 in the HFSC group were finally evaluated. In the APC group 72 patients (96 %) were successfully treated with the assigned treatment alone vs. 73 (96 %) in the HFSC group. Initial endoscopic hemostasis using a single or combined modality was achieved in all patients. Recurrent bleeding within 30 days was experienced by five patients (6.7 %) and seven patients (9.2 %) in the AFC and HFSC groups, respectively (P = 0.563), and within 7 days by three patients (4.0 %) and five patients (6.6 %), respectively (P = 0.719). We found no significant difference in the rates of adverse events (1.3 % vs. 2.6 %) or mortality (2.7 % vs. 2.6 %) between the groups. CONCLUSIONS The efficacy and safety of soft coagulation using endoscopic hemostatic forceps is not inferior to APC when used to treat patients with bleeding peptic ulcers. Clinicaltrials.gov NCT02020603.

Epidemiological changes in hepatitis A in Korea: increasing age and its effect on clinical outcomes

Korea has recently experienced an increasing number of acute hepatitis A cases. We investigated the dynamics of hepatitis A and changes in the mean age of patients in a hospital in Seoul, Korea. Mean age increased consistently from 19 years in 1996 to 30 years in 2009 (P < 0·0001). Between two acute hepatitis A outbreaks in 1998-1999 and in 2008-2009, mean age increased from 23 to 30 years (P < 0·001). However, the hepatitis A clinical outcomes were similar between the outbreaks. Duration of hospital stay, creatinine level and prothrombin time did not differ. Throughout the study period, individuals born in the 1970s and 1980s comprised the largest proportion (84%) of patients. As this susceptible generation ages, the mean age of hepatitis A patients in Korea will increase consistently. However, at present, the impact of increasing age on clinical outcomes is not apparent.