Association between cotinine-verified smoking status and risk of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: The relationship between cigarette smoking and nonalcoholic fatty liver disease (NAFLD) has been controversial. Most relevant studies have relied on self-reported questionnaires. We aimed to elucidate the association between smoking status and NAFLD using an objective biomarker of tobacco exposure (urinary cotinine) and self-reported questionnaire. METHODS: A cross-sectional study was conducted on 160 862 asymptomatic examinees who underwent abdominal ultrasonography and urinary cotinine measurements between April 2011 and December 2015. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50 ng/mL. RESULTS: The mean age of the study population was 36.1 years, and the proportion of men was 51.7%. The proportions of self-reported and cotinine-verified current smokers were 17.6% and 17.7% respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of NAFLD (adjusted odds ratio [AOR], 1.10; 95% confidence interval [CI], 1.06-1.14). Moreover, among the current smokers, the risk of NAFLD increased with an increase in the amount of cigarette smoking (<10 and ≥10 pack-years vs never smokers; AOR, 1.04 and 1.11; 95% CI, 1.01-1.08 and 1.05-1.16 respectively). Cotinine-verified current smoking was also associated with an increased risk of NAFLD (AOR, 1.10; 95% CI, 1.06-1.14). CONCLUSIONS: Cotinine-verified current smoking and self-reported current smoking were independent risk factors for NAFLD. Further longitudinal studies are needed to more clearly elucidate the impact of smoking on the development of NAFLD.

Natural courses of branch duct intraductal papillary mucinous neoplasm.

PURPOSE: The study was done to elucidate the clinico-radiologic predictive factors for cancerous change detected by disease progression (PD) mainly defined by interval increase in cyst size and change of cyst morphology, for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) patients with relatively long-term follow-up. METHODS: Retrospective analysis of medical records and imaging findings were performed on 107 patients with BD-IPMN enrolled from July 2005 to May 2013, in whom the communication between the cystic lesion and pancreatic duct was confirmed by either endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: During the mean ± SD follow-up period of 51.5 ± 24.5 months, PD was noticed in 43 (40.2%) of 107 BD-IPMN patients. Among these 107 patients, 21 (19.6%) displayed cancerous change. By univariate analyses, septated/multilocular cyst morphology, cyst size larger than 30 mm, cyst wall thickening, mural nodules, and the presence of symptoms were significant predictive factors for cancerous changes in BD-IPMN patients. A Cox forward stepwise linear regression model revealed that cyst wall thickening (OR 9.187, 95% CI 1.883~44.820, P < 0.01) and mural nodules (OR 6.224, 95% CI 1.311~29.549, P = 0.021) were significant and independent predictive factors for cancerous change in BD-IPMN patients. CONCLUSIONS: A significant proportion of patients with BD-IPMN showed PD and cancerous change during the long-term follow-up. Cyst wall thickening and mural nodules were significant and independent predictive factors of cancerous change in patients with BD-IPMN.

Increased Risk of Advanced Colorectal Neoplasia Among Korean Men With Metabolic Abnormality and Obesity.

BACKGROUND & AIMS: Obesity and metabolic abnormality are risk factors for colorectal cancer and adenoma. We evaluated the risk of advanced colorectal neoplasm (AN) according to metabolic status and obesity in Koreans. METHODS: We performed a retrospective cross-sectional study of 70,428 individuals in Korea who underwent colonoscopy and whose metabolic state and body mass index were examined, from 2003 through 2012, at Kangbuk Samsung Hospital in Korea. We calculated odds ratios (ORs) for AN in people who were metabolically healthy but obese, people with metabolic abnormality who were not obese, and people with metabolic abnormality who were obese. The reference group was metabolically healthy nonobese peoples. AN was defined as adenoma ≥10 mm in diameter, adenoma with any component of villous histology, high-grade dysplasia, or invasive cancer. RESULTS: No increased risk of AN was observed in the metabolically healthy but obese (OR, 0.99; 95% confidence interval [CI], 0.67-1.46; P = .825) and metabolic abnormality who were not obese groups (OR, 1.01; 95% CI, 0.85-1.21; P = .765). In contrast, risk of AN was increased in the metabolic abnormality who were obese group (OR, 1.33; 95% CI, 1.12-1.58; P = .006). In men, risk of AN showed a greater increase in the metabolic abnormality who were obese group (OR, 1.48; 95% CI, 1.20-1.83; P = .001). This association was not observed in women (OR, 1.21; 95% CI, 0.84-1.75; P = .476). CONCLUSIONS: Men with 1 or more metabolic abnormality and obesity are at increased risk for AN.

Endosonographer's macroscopic evaluation of EUS-FNAB specimens after interactive cytopathologic training: a single-center prospective validation cohort study.

BACKGROUND: In many centers, rapid on-site evaluation (ROSE) for the specimens obtained from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is not available. The aim of this study was to compare the diagnostic yields of EUS-FNAB in the presence or absence of ROSE. METHODS: Seventy-five patients who underwent EUS-FNAB for the pancreatic, gastric subepithelial, and mesenteric mass lesions at our institution from November 2013 to August 2014 were included. For 20 patients in the pilot cohort, EUS-FNAB was performed with ROSE, and simultaneously, training of the staff endosonographer for tissue adequacy by an on-site cytopathologist was also performed. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EUS-FNAB in the pilot cohort were 91.7, 100.0, 100.0, 88.9, and 95.0 %, respectively. The 3.2 ± 0.8 [mean ± standard deviation (SD)] needle passes were needed in this cohort. Fifty-five patients were enrolled as a validation cohort from April 2014 to August 2014, and tissue adequacies were assessed by an experienced endosonographer without ROSE in this cohort. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNAB in this validation cohort were 92.1, 100.0, 100.0, 85.0, and 94.6 %, respectively. The 4.5 ± 0.6 (mean ± SD) needle passes were needed in this cohort (p < 0.01 compared to pilot cohort). CONCLUSIONS: Diagnostic accuracy of EUS-FNAB in which the adequacy of sample was assessed by an attending endosonographer was acceptable. This study suggests that on-site evaluation by a trained endosonographer may be an alternative tool to ROSE where ROSE is not available.

Risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years.

BACKGROUND: Very little is known about risk factors associated with colorectal neoplasia in persons aged <50 years. In particular, there has been no study thus far focusing on the risk factors for colorectal neoplasia in persons aged 30 to 39 years. OBJECTIVE: To investigate risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years and to compare those data with those of persons aged 50 to 59 years. DESIGN: Cross-sectional observational study. SETTING: Screening center in a university hospital in Korea. PATIENTS: A cohort of 28,504 Korean adults (13,678 aged 30-39 years, 12,507 aged 40-49 years, and 2319 aged 50-59 years) who underwent colonoscopy as part of their routine preventive health care. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years. RESULTS: In the 30-to-39-years group, male sex, smoking, fatty liver, metabolic syndrome (MetS), obesity, elevated fasting blood glucose levels, and elevated triglyceride levels were associated with overall neoplasia, whereas for advanced neoplasia, the independent risk factors were smoking, fatty liver, and elevated triglyceride levels. Moreover, the prevalence of overall neoplasia in men aged 30 to 39 years exhibiting all risk factors was not lower than that in average-risk women aged >50 years (20.8% vs 18.8%; P = .546). The risk factors of overall neoplasia in the 40-to-49-years group were similar to those in the 30-to-39-years group. For advanced neoplasia, the independent risk factors in the 40-to-49-years group were male sex, smoking, MetS, and obesity. LIMITATIONS: Selection bias may exist for participants of ethnic Korean heritage in 2 centers. CONCLUSION: Obese male smokers with fatty liver and MetS might benefit from screening colonoscopy starting before age 50 years.

Associations Between Parameters of Glucose and Lipid Metabolism and Risk of Colorectal Neoplasm.

BACKGROUND: Diabetes and dyslipidemia have been linked to an increased risk of colorectal neoplasm (CRN). However, previous studies evaluating these associations have shown inconsistent results, and large-scale studies are few in number. AIM: To investigate the associations between the parameters of glucose and lipid metabolism and the presence of CRN. METHODS: A cross-sectional study was performed on 38,490 Korean adults aged ≥30 years undergoing their first colonoscopy as part of routine preventive health care between 2010 and 2011. RESULTS: The prevalence of overall CRN increased with increasing levels of glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) and with decreasing level of apolipoprotein A1 (ApoA1). The adjusted prevalence ratios for overall CRN comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, triglycerides, total cholesterol, LDL-C, ApoB, and ApoA-1 were 1.83 (95% CI 1.62-2.06), 1.17 (95% CI 1.03-1.33), 1.09 (95% CI 0.97-1.23), 1.22 (95% CI 1.08-1.37), 1.31 (95% CI 1.16-1.48), 1.19 (95 % CI 1.07-1.33), 1.38 (95% CI 1.23-1.54), 1.30 (95% CI 1.14-1.47), and 0.85 (95% CI 0.76-0.95), respectively. There was also a significant association between higher levels of glucose, LDL-C, and ApoB with a higher prevalence of advanced CRN. Moreover, the risk of CRN increased further in cases in which the parameters of glucose metabolism and lipid metabolism worsened simultaneously. CONCLUSIONS: The levels of parameters of glucose and lipid metabolism are significantly associated with the prevalence of CRN. Altered glucose and lipid metabolism may contribute to the development of CRN.

Radiologic response to transcatheter hepatic arterial chemoembolization and clinical outcomes in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: The current study analysed the association between radiologic tumour response and survival times of patients with hepatocellular carcinoma (HCC) who were treated with transcatheter hepatic arterial chemoembolization (TACE). METHODS: Among 493 consecutive patients presenting to our institution between July 2002 and June 2010 with radiologically (n = 398) or histologically (n = 95) confirmed HCC, 368 patients who met inclusion criteria, underwent TACE and had confirmed survival data were retrospectively reviewed. The radiologic response was assessed using RECIST 1.1, EASL and mRECIST criteria at 1 month after the initial TACE. RESULTS: By univariate analysis, higher Child-Turcotte-Pugh (CTP) score, bilobar and multifocal distribution of tumours, larger tumour size (>5 cm), higher serum alpha-foetoprotein (AFP) level (>200 ng/ml), no subsequent radiofrequency ablation, advanced ECOG, UNOS and BCLC staging, absence of complete necrosis and non-responder (SD or PD) in RECIST 1.1, EASL and mRECIST response assessment were significantly associated with shorter overall survival times. By Cox proportional hazards model, advanced age, presence of ascites, higher MELD score, advanced BCLC staging, absence of complete necrosis and non-responder by RECIST 1.1, EASL and mRECIST criteria were independent and significant prognosticators for overall survival times in patients with HCC who underwent TACE. By time-dependent ROC curve analysis, mRECIST response criteria showed greatest accuracy in predicting survival (AUROC = 0.8676), followed by EASL (AUROC = 0.8471) and RECIST 1.1 (AUROC = 0.7986). CONCLUSION: mRECIST and EASL criteria for assessing radiologic response 1 month after initial TACE more consistently predict the differences in overall survival between responders and non-responders than conventional RECIST 1.1 criteria.

Comparison of brush and basket cytology in differential diagnosis of bile duct stricture at endoscopic retrograde cholangiopancreatography.

BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD: The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS: We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 (14.9%) and 107 patients (93.9%), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively (P=0.347 and 0.827 for sensitivity and accuracy, respectively). The good and excellent cellular yields (≥grade 2) were obtained by Geenen brush and Dormia basket cytology in 88 (77.2%) and 79 (69.3%) patients, respectively. CONCLUSION: The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.

Complete biopsy resection of diminutive polyps.

BACKGROUND AND STUDY AIMS: Cold biopsy forceps polypectomy (CBP) is commonly used for the removal of diminutive polyps; however, evidence for the efficacy of CBP is lacking. The aim of this study was to evaluate the adequacy of resection of diminutive polyps and to identify predictors for complete resection using CBP. PATIENTS AND METHODS: This was a prospective study from a tertiary referral hospital in Korea. A total of 196 patients were screened, and 65 patients with diminutive polyps were enrolled. CBP was used to resect diminutive polyps until no polyp was visible by chromoendoscopy using indigo carmine spray. Each polyp base was then resected using endoscopic mucosal resection (EMR) with a 1-3-mm free margin. CBP and EMR specimens were sent to the histopathology department for the evaluation of the completeness of the resection. Cross sections of the EMR specimens made at 1-mm intervals were examined by a pathologist. RESULTS: A total of 86 diminutive polyps were available for assessment. Overall, 90.7% (78/86) of the diminutive polyps were completely resected using CBP (95%CI 84.6-96.8%). The complete resection rate for all diminutive adenomas was 92.3 % (60/65; 95%CI 85.8-98.8%) and for 1-3-mm adenomas 100% (95%CI 81.5-100%). Polyp size, histology, and location, and number of biopsies were not different between the complete and incomplete resection groups. CONCLUSIONS: In this small study approximately 90 % of all diminutive polyps and 100% of 1-3-mm adenomatous polyps were completely resected using CBP and chromoendoscopy. CBP appears to be adequate for the resection of the majority of diminutive polyps, especially small sized adenomas (≤ 3 mm) if no residual tissue is visible by chromoendoscopy.

Apolipoprotein B/AI ratio is independently associated with non-alcoholic fatty liver disease in nondiabetic subjects.

BACKGROUND AND AIMS: The apolipoprotein B/AI (ApoB/AI) ratio is a strong new risk factor for cardiovascular (CV) disease. Although recent reports have shown the effects of non-alcoholic fatty liver disease (NAFLD) on CV disease, NAFLD is under-recognized as a predictable risk factor for CV disease. This study was performed to assess the independent association between ApoB/AI ratio and NAFLD. METHODS: This cross-sectional study was performed in 9162 subjects who participated in a health checkup program in South Korea in 2009. The presence of NAFLD was defined by ultrasonographic examination. Logistic regression analysis was applied to estimate the association between ApoB/AI ratio and NAFLD. The odds ratio (OR) and P were estimated according to the categorized level of the ApoB/AI ratio. RESULTS: The overall prevalence of NAFLD was 27.9% (n = 2554, 41.7% of the men, 10.8% of the women). Men had a 5.91-fold (95% CI 5.28-6.62) greater risk for NAFLD than women. After adjusting for confounding factors, the ApoB/AI ratio was more closely associated with the prevalence of NAFLD than with any other lipid profiles (OR 8.537 in men, 16.6 in women). NAFLD risk increased as the quartiles of the ApoB/AI ratio increased from the first to the fourth quartile (OR 1.359, 2.173 and 3.124, P for trend < 0.001). CONCLUSION: The ApoB/AI ratio was associated with the prevalence of NAFLD in nondiabetic subjects and was independent of obesity and other metabolic components. This result suggests that NAFLD may provide additional information for atherosclerosis progression and CV risks.

Clinical impact of extended-spectrum ß-lactamase-producing Enterobacteriaceae in patients with biliary tract infection.

BACKGROUND: Clinical outcomes associated with Gram-negative bacterial isolates with extended spectrum beta-lactamase (ESBL) in patients with biliary tract infection are largely unknown. The objective of the present study was to compare the demographics, risk factors, and clinical outcomes between patients with biliary tract infection caused by ESBL-producing and non-producing Klebsiella pneumoniae and Escherichia coli. METHODS: Between February 2005 and August 2010, we collected 159 cases with biliary tract infection caused by K. pneumoniae and E. coli identified by blood or bile cultures obtained before endoscopic or surgical treatment performed at our institution. We also retrospectively collected the data of patients' demographic characteristics, co-morbid conditions, antimicrobial therapy, and clinical outcomes. RESULTS: Among the 159 strains isolated, 21 strains (13.2 %) were positive for phenotypical ESBL-test. Sepsis was more common in ESBL-positive strains, but did not reach statistical significance (23.8 % for ESBL-positive strains and 9.4 % for ESBL-negative strains, P = 0.066). Thirty-day mortality was significantly higher in ESBL-positive strains (3/21, 14.3 %) compared to ESBL-negative strains (4/138, 2.9 %, P = 0.049). However, there were no significant differences in overall survival between ESBL-positive and ESBL-negative strains. By multivariate analysis, inadequate antimicrobial therapy (HR 4.06, 95 % CI 1.08-16.46, P = 0.049) and sepsis (HR 6.54, 95 % CI 1.26-33.85, P = 0.025) were independent and significant predictors of 30-day mortality. CONCLUSION: ESBL status of bacterial isolates for patients with biliary tract infection caused by K. pneumoniae and E. coli has clinical impact, especially on the short-term outcomes of those patients.

Association between atrophic gastritis and gastroesophageal reflux symptoms.

BACKGROUND/AIMS: Atrophic gastritis may be inversely associated with gastroesophageal reflux disease (GERD) symptoms. The aim of this study was to determine the association between GERD symptoms, endoscopic atrophy grade, and histologic atrophy score. METHODOLOGY: A total of 1,555 consecutive subjects who underwent esophagogastroduodenoscopy for health check-ups were enrolled prospectively. All persons were given a self-reported questionnaire for GERD symptoms (heartburn and/or regurgitation) and were classified into the following two groups: GERD symptoms group and no GERD symptoms group. Endoscopic grade of atrophic gastritis was assessed by the atrophic pattern system. The histologic atrophy score was evaluated semi-quantitatively by the updated Sydney classification. RESULTS: Of the 1,555 patients, 314 (20.2%) had GERD symptoms at least once a week and 1,241 (79.8%) had no GERD symptoms. The prevalence of the O-type atrophic gastritis (4.1% vs. 8.9%) and moderate or severe atrophic gastritis (1.9% vs. 4.8%) was significantly lower in the GERD symptoms group (p <0.05). The association between GERD symptoms and moderate or severe atrophic gastritis persisted after adjustment for potential confounders (p = 0.012). Of the 304 subjects who underwent endoscopic biopsies, 57 (18.8%) and 247 (81.2%) were in the GERD symptoms and no symptoms groups, respectively. There were no significant differences in H. pylori infections, H. pylori density, neutrophil activity, and degree of inflammation between the two groups. However, the scores of intestinal metaplasia and glandular atrophy were significantly lower in the GERD symptoms group (p <0.05). CONCLUSIONS: GERD symptoms are inversely associated with the endoscopic atrophy grade and the histologic atrophy score.

Association between red cell distribution width and disease activity in patients with inflammatory bowel disease.

BACKGROUND: Recent studies have suggested that a higher red blood cell distribution width (RDW) is associated with disease activity in patients with inflammatory bowel disease (IBD). However, the RDW in IBD patients without anemia has not been investigated. AIM: This study aimed to determine whether or not RDW could be used for the assessment of disease activity in IBD patients with and without anemia. METHODS: The serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), hemoglobin concentration, platelet and white blood cell counts, and RDW were assessed in 221 IBD patients, comprised of 120 patients with ulcerative colitis (UC) and 101 patients with Crohn's disease (CD). Disease activity was determined for UC and CD with the Mayo score and the Crohn's disease activity index, respectively. RESULTS: The CRP level, ESR, hemoglobin concentration, hematocrit, and RDW increased according to disease activity in patients with and without anemia (all P < 0.05). Multivariate analysis demonstrated that RDW was the best independent indicator for predicting disease activity in CD patients without anemia [odd ratios (OR), 1.702; 95% confidence interval (CI), 1.185-2.445; P = 0.004] and UC patients without anemia (OR, 4.921; 95% CI, 2.281-10.615; P < 0.001). Also, ROC curve analysis showed the RDW to be the most significant indicator of non-anemic active IBD [area under curve (AUC) in CD, 0.852, P < 0.001; AUC in UC, 0.827, P < 0.001]. CONCLUSION: The association between increased RDW and active IBD was evident in IBD patients with and without anemia.

Clinical usefulness of endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening.

BACKGROUND AND AIMS: The differential diagnosis of gallbladder (GB) cancer from inflammatory diseases in patients with a thickened GB wall is difficult, whereas the pre-operative diagnosis of GB cancer is critical for selecting the appropriate surgical modality. We evaluated the clinical usefulness of endoscopic ultrasonography (EUS) for the differential diagnosis of GB wall thickening. METHODS: The medical records, post-operative pathology reports, and images of EUS for 134 patients with GB wall thickening (>3 mm) who underwent laparoscopic or open cholecystectomies at our institution between December 2006 and February 2010 were retrospectively reviewed. RESULTS: Thirteen patients (9.7%) had neoplastic GB wall thickening (11 with adenocarcinomas and two with adenosquamous carcinomas) and the remaining 121 patients (90.3%) had non-neoplastic GB wall thickening (117 with inflammatory GB wall thickening and four with adenomyomatosis). The mean (± standard deviation [SD], mm) GB wall thickness was 6.5 ± 3.3 and 19.4 ± 7.7 for non-neoplastic and neoplastic GB wall thickening, respectively (P < 0.01). The EUS variables which had a statistically significant association with neoplastic GB wall thickening were GB wall thickening >10 mm, disruption of the normal two layers of the GB wall, hypoechoic internal echogenecity, and the absence of gallstones. Based on the multivariate analyses, GB wall thickening >10 mm and hypoechoic internal echogenecity were independent predictive factors for neoplastic GB wall thickening. CONCLUSIONS: The diagnostic power of EUS for differentiating neoplastic and non-neoplastic GB wall thickening could be improved by the appropriate application of some EUS variables.

Optimal number of endoscopic biopsies in diagnosis of advanced gastric and colorectal cancer.

Endoscopic biopsy is necessary to confirm a histopathologic diagnosis. Currently, 6 to 8 biopsies are recommended for diagnosis of a suspected malignant lesion. However, multiple biopsies may result in several problems, such as an increased risk of bleeding, procedure prolongation, and increased workload to pathologists. The aim of this study was to clarify the optimal number of endoscopic biopsy specimens required in diagnosis of advanced gastrointestinal cancer. Patients who were diagnosed with advanced gastrointestinal cancer during endoscopy were included. Five specimens were obtained sequentially from viable tissue of the cancer margin. Experienced pathologists evaluated each specimen and provided diagnoses. A total of 91 patients were enrolled. Fifty-nine subjects had advanced gastric cancer, and 32 had advanced colon cancer. Positive diagnosis rates of the first, second, and third advanced gastric cancer specimens were 81.3%, 94.9%, and 98.3%, respectively, while positive diagnosis rates of advanced colon cancer specimens were 78.1%, 87.5%, and 93.8%. Further biopsies did not increase positive diagnosis cumulative rates. This study demonstrated that three specimens were sufficient to make correct pathologic diagnoses in advanced gastrointestinal cancer. Therefore, we recommend 3 or 4 biopsies from viable tissue in advanced gastrointestinal cancer to make a pathologic diagnosis during endoscopy.

Increased intestinal permeability as a predictor of bacterial infections in patients with decompensated liver cirrhosis and hemorrhage.

BACKGROUND AND AIM: There have been no trials comparing the prophylactic effect of oral quinolone and intravenous cephalosporin antibiotics and elucidating the predictive factors for the occurrence of bacterial infections in cirrhotic patients with gastrointestinal bleeding in Asian-Pacific region. METHODS: One hundred and thirteen patients with advanced liver cirrhosis and active gastrointestinal hemorrhage were enrolled in our study. The patients were randomly allocated into either the oral ciprofloxacin group (n = 50, 500 mg every 12 h) or the intravenous ceftriaxone group (n = 63, 2.0 g per day for 7 days). RESULTS: Proven or possible infections were significantly more frequent in the patients in the oral ciprofloxacin group (34.0%) than the intravenous ceftriaxone group (14.3%, P = 0.002). The intestinal permeability index (IPI, mean [SD]) measured the day after admission was significantly higher in the patients with proven or possible infections (1.45 [0.96]) compared with the no infection group (0.46 [0.48], P <0.01). By multivariate analysis, oral ciprofloxacin prophylaxis and higher IPI at the time of inclusion were independent and significant predictors for proven or possible infections. By receiver operating characteristic curve analysis, the best cutoff value of IPI for the prediction of the occurrence of bacterial infection was 0.62%. CONCLUSIONS: The frequency of proven or possible infections was significantly lower in the intravenous ceftriaxone group compared with the oral ciprofloxacin group. The IPI measured the day after admission is a good clinical parameter predicting the occurrence of infection in these patients.

The role of the gut barrier function in the pathophysiology of viral liver cirrhosis.

BACKGROUND/AIMS: Plasma endotoxin levels commonly increase in patients with liver cirrhosis. We purposed to identify change of intestinal permeability and frequency of endotoxemia in patients with viral liver cirrhosis. Additionally, we studied the relationship between plasma endotoxin levels and failure of gut barrier function. METHODOLOGY: Subjects included 27 patients with viral liver cirrhosis (LC) and 45 volunteers as healthy control (HC). Intestinal permeability index was determined by the level of urinary excretion of polyethylene-glycol after oral administration and plasma endotoxin levels by using quantitative Limulus assay. Grades of liver dysfunction were categorized by Child-Pugh classification and MELD score. RESULTS: Intestinal permeability indexes were higher in LC than in HC (1.48±0.56%, n=27 vs. 0.93±0.50%, n=45, p=0.019). Plasma endotoxin levels were higher in LC than in HC (0.35±0.17EU/ mL vs. 0.11±0.14EU/mL, p<0.001). In LC, plasma endotoxin levels progressively increased in relation to severity of liver dysfunction (Child-Pugh class A (0.31±0.17EU/mL), B (0.37±0.14EU/mL) and C (0.42±0.23EU/mL), p=0.013, MELD category 1/2/3/4=0.27±0.14/0.39±0.17/0.32±0.21/0.47±0.28E U/mL, p=0.043). LC with/without portal hypertension (1.47±0.55%, p<0.01/1.29±0.59%, p<0.05) had higher intestinal permeability indexes than HC (0.93±0.50%). CONCLUSIONS: Severity of liver dysfunction was associated with endotoxemia. Although gut barrier function did not show a significant relationship with endotoxemia, increased intestinal permeability may be a significant finding that at least in part is associated with the pathophysiology of viral liver cirrhosis.

Microsatellite instability in young patients with sporadic colorectal adenomas.

BACKGROUND/AIMS: This study was designed to determine the prevalence of microsatellite instability (MSI) among colorectal adenomas detected in patients ≤ 40 years of age and to compare the prevalence of MSI in young (≤ 40 years) and older (>40 years) patients with colorectal adenomas. Additionally, we attempted to identify the underlying cause of MSI in these patients. METHODOLOGY: We prospectively tested for the presence of MSI using five NCI markers in samples from the two patient groups. The frequency of MSI was compared and the underlying causes of MSI were determined by methylation specific PCR and germ-line mutation analysis for mismatch repair genes. RESULTS: The frequency of MSI was higher in the ≤ 40 group than the >40 group (31.4% and 6.4%, respectively, p=0.0004). The MSI-high pattern was also more prevalent in the ≤ 40 group than the >40 group (15.7% and 2.5%, respectively, p=0.014). The hypermethylated hMLH1 gene was demonstrated in 7/8 (87.5%) patients with MSI-high in the ≤ 40 group and in 1/2 (50.0%) patients with MSI-high in the >40 group. No study subject showed a germline mutation of hMLH1 or hMSH2. CONCLUSIONS: MSI-high was more frequent in young (≤ 40 years) patients with colorectal adenoma than in older (>40 years) patients. Hypermethylation of the hMLH1 gene appears to be an important cause of MSI-high in these patients.

Comparison between clevudine and entecavir treatment for antiviral-naïve patients with chronic hepatitis B.

BACKGROUND AND AIMS: There has been no study comparing the clinical efficacy of clevudine and entecavir in antiviral-naïve patients with chronic hepatitis B (CHB). METHODS: A total of 128 antiviral-naïve CHB patients were included to receive clevudine 30 mg (n=55) or entecavir 0.5 mg (n=73) once daily for a mean follow-up period of 18.4 months. RESULTS: Thirty-three (60.0%) in the clevudine group and 40 (54.8%) in the entecavir group were HBeAg positive (P>0.05). At 6 months from the baseline, the mean decreases in HBV-DNA were 4.86 and 4.72 log(10) copies/ml in the clevudine and entecavir groups respectively (P>0.05). The proportion of patients with undetectable serum HBV-DNA (<300 copies/ml) at 6 months was 65.5 and 74.0% in the clevudine and entecavir groups respectively (P>0.05). The proportion of patients with normal alanine aminotransferase levels at 6 months was 74.5 and 84.9% in the clevudine and entecavir groups respectively. During the mean follow-up of 18.4 months, genotypic resistance was noted in three patients (5.5%) in the clevudine group and no cases in the entecavir group. Eight patients (14.6%) in the clevudine group experienced symptoms, signs and laboratory abnormalities relevant to clevudine-induced myopathy. CONCLUSIONS: Clevudine and entecavir treatment effectively suppresses HBV replication in most antiviral-naïve patients with CHB. During a mean follow-up of 18.9 months, a small proportion (5.5%) of patients in the clevudine group developed genotypic resistance. However, a substantial proportion (14.6%) of patients in the clevudine group had an adverse effect of clevudine-induced myopathy.

The effect of probiotics and mucoprotective agents on PPI-based triple therapy for eradication of Helicobacter pylori.

BACKGROUND/AIMS: Recent studies have found that probiotics have anti-Helicobacter pylori (HP) properties. We evaluated the additive effects of (i) Saccharomyces boulardii combined with proton pump inhibitor (PPI)-based triple therapy and (ii) S. boulardii and a mucoprotective agent (DA-9601) coupled with PPI-based triple therapy for HP eradication. METHODS: We recruited 991 HP infected patients and randomized them into one of three groups, (A) PPI-based 7-day triple therapy, (B) the same triple therapy plus S. boulardii for 4 weeks, and (C) the same 7-day triple therapy plus S. boulardii and mucoprotective agent for 4 weeks. All patients in the three groups were tested via (13)C-urea breath test 4 weeks after the completion of the therapy. RESULTS: According to the results of an intention-to-treat analysis, HP eradication rates for the groups A, B, and C were 71.6% (237/331), 80.0% (264/330), and 82.1% (271/330), respectively (p = .003). According to the results of a per protocol analysis, the eradication rates were 80.0% (237/296), 85.4% (264/309) and, 84.9% (271/319), respectively (p = .144). The frequency of side effects in group B (48/330) and C (30/330) was lower than that in group A (63/331) (p < .05). CONCLUSION: This study suggests that supplementation with S. boulardii could be effective for improving HP eradication rates by reducing side effects thus helping completion of eradication therapy. However, there were no significant effects on HP eradication rates associated with the addition of mucoprotective agents to probiotics and triple therapy.