Characteristics of advanced gastric cancer undetected on gastroscopy.

BACKGROUND/AIMS: Stomach cancer can be easily diagnosed via endoscopy, but also possible to be missed. The aim of this study was to investigate the clinical and endoscopic characteristics of advanced gastric cancers that were not diagnosed based on endoscopic examination. METHODS: We evaluated patients who had newly diagnosed advanced gastric cancer that was undetected via endoscopy within the last six months. RESULTS: Sixteen patients were included in this study. The locations of the cancers were the cardia in six cases, the greater curvature side of the body in eight cases and the antrum in two cases. The histological findings were tubular type adenocarcinoma in 11 cases, with ten cases of moderately to poorly differentiated adenocarcinoma and five cases of signet ring cell type adenocarcinoma. CONCLUSIONS: Even advanced gastric cancer lesions may not be detected during endoscopy. If a patient continues to complain of upper gastrointestinal symptoms, even though endoscopy does not find abnormal findings, repeated endoscopy and/or additional diagnostic studies should be considered.

Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloride-treated rat livers.

AIMS: Defects in intrahepatic nitric oxide (NO) are attributed to reduced blood flow due to portal hypertension caused by diminished endothelial NO synthase (eNOS) activity. The aim of this study is to identify the therapeutic effects of silymarin on eNOS/NO-related enzymes and hepatic enzymes in carbon tetrachloride (CCl4)-induced cirrhotic rats. MAIN METHODS: CCl4 treated for 12 weeks was discontinued and then administrated with silymarin daily for 4 weeks. Collagen concentrations were determined by measuring hydroxyproline content. Serum was assayed for hepatic enzymes like alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities. NOS activities were measured by oxyhemoglobin oxidation assay, and levels of enzyme expression and phosphorylation were detected by Western-blot analyses. KEY FINDINGS: Silymarin treatment restored the values for collagen content and ALT and ALP activities when compared to the values with spontaneous resolution following discontinuation of CCl4. CCl4 treatment highly increased eNOS expression and NOS activity in livers, but the phosphorylation was markedly decreased. Silymarin decreased significantly eNOS expression and activity. Expression and/or phosphorylation of enzymes activating eNOS were unchanged (Akt and AMPK) or decreased (PKA) by silymarin. Especially, the expression of caveolin-1, an inhibitor of eNOS was unchanged by CCl4, but its phosphorylation was significantly increased. However, silymarin markedly increased caveolin-1 expression but decreased its phosphorylation to expression. SIGNIFICANCE: These results suggest that chronic silymarin treatment can improve cirrhosis-induced liver enzyme activities and fibrosis, but may aggravate the hemodynamic eNOS activity, particularly by decreasing eNOS expression and increasing caveolin-1 expression.

Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease.

OBJECTIVE: The association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and metabolic syndrome has been documented for obese men and middle-aged men. This study was designed to determine the relationship between NAFLD and the oral glucose tolerance test (OGTT) to predict preclinical diabetes in nondiabetic young male patients (<30 years old). METHODS: A total of 75 male patients who had elevated liver enzymes and who were diagnosed with NAFLD were enrolled in this study. A standard 75 g OGTT was carried out on all patients. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined as a fasting plasma glucose (FPG) level > or =100 mg/dl but <126 mg/dl, and a 2-h post-load glucose on the OGTT of > or =140 mg/dl, but <200 mg/dl respectively. RESULTS: According to the OGTT results, 24 (32%) patients were diagnosed as having IGT and 12 (16%) patients were diagnosed as having diabetes. Among the 48 patients with normal fasting glucose, 18 (37.6%) patients showed abnormal glucose tolerance (15 had IGT and three had diabetes). The NAFLD patients with abnormal glucose tolerance showed significant differences in age, weight, body mass index, waist-hip ratio, alanine aminotransferase, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, triglyceride, insulin, FPG and homeostasis model for insulin resistance (HOMA-IR). Multiple regression analysis showed that age, FPG and HOMA-IR were independent predictors of abnormal glucose tolerance. CONCLUSIONS: Although the patients were young men, an OGTT should be recommended for NAFLD patients with elevated liver enzymes and IFG to predict the risk of type 2 diabetes.

Outcome of laparoscopic cholecystectomy is not influenced by chronological age in the elderly.

AIM: To evaluate the outcome of laparoscopic cholecystectomy (LC) in patients aged 80 years and older. METHODS: A total of 353 patients aged 65 to 79 years (group 1) and 35 patients aged 80 years and older (group 2) underwent LC. Patients were further classified into two other groups: those with uncomplicated gallbladder disease (group A) or those with complicated gallbladder disease (group B). RESULTS: There were no significant differences between the age groups (groups 1 and 2) with respect to clinical characteristics such as age, gender, comorbid disease, or disease presentation. Mean operative time, conversion rate, and the incidence of major postoperative complications were similar in groups 1 and 2. However, the percentage of high-risk patients was significantly higher in group 2 than in group 1 (20.0% vs 5.7%, P < 0.01). Group A comprised 322 patients with a mean age of 71.0 +/- 5.3 years, and group B comprised 51 patients with a mean age of 69.9 +/- 4.8 years. In group B, mean operative time (78.4 +/- 49.3 min vs 58.3 +/- 35.8 min, P < 0.01), mean postoperative hospital stay (7.9 +/- 6.5 d vs 5.0 +/- 3.7 d, P < 0.01), and the incidence of major postoperative complications (9.8% vs 3.1%, P < 0.05) were significantly greater than in group A. The conversion rate tended to be higher in group B, but this difference was not significant. CONCLUSION: Perioperative outcomes in elderly patients who underwent LC seem to be influenced by the severity of gallbladder disease, and not by chronologic age. In octogenarians, LC should be performed at an earlier, uncomplicated stage of the disease whenever possible to improve perioperative outcomes.

Hepatic steatosis and fibrosis in young men with treatment-naïve chronic hepatitis B.

OBJECTIVES: The clinical significance of liver steatosis has been studied because steatosis plays a role in the progression of liver fibrosis. Nevertheless, the impact of steatosis in the early stage of fibrosis in non-obese young men with chronic hepatitis B (CHB) is poorly understood. Thus, the purpose of this study was to investigate the prevalence of hepatic steatosis, assess the relationship between hepatic steatosis and fibrosis and to assess the laboratory parameters for predicting clinically significant liver fibrosis in non-obese young men with CHB. METHODS: We prospectively evaluated liver biopsies in young male patients with CHB with a serum alanine aminotransferase level of more than two times the upper limit of normal for at least 3 months before enrollment. Patients were excluded when they had co-infection with another virus and prior antiviral treatment. Demographical, anthropometric and laboratory parameters were analysed. Liver steatosis, necroinflammation and fibrosis were also assessed. RESULTS: A total of 86 young male patients with CHB were included in this study. The median age was 21 years (range, 20-26 years) and the median body mass index was 23.0 kg/m2 (range, 18.0-28.3 kg/m2). Steatosis was present in 44 patients (51.2%). Significant fibrosis (beyond periportal fibrosis) was present in 50 patients (58.1%). Steatosis was associated with insulin, homeostasis model for insulin resistance (HOMA-IR), total cholesterol and triglycerides. On multiple regression analysis, steatosis was independently associated with triglyceride and HOMA-IR. Significant fibrosis was independently associated with gamma-glutamyltransferase (GGT) and necroinflammation activity. However, there was no significant association between significant fibrosis and the presence of steatosis. CONCLUSIONS: The prevalence of hepatic steatosis is a common finding in young male patients with CHB. Hepatic steatosis in CHB patients seems to be associated with insulin resistance, but it is not associated with hepatic fibrosis. GGT levels can provide useful information on the stage of CHB.

Pre-operative predictive factors for gallbladder cholesterol polyps using conventional diagnostic imaging.

AIM: To determine the clinical data that might be useful for differentiating benign from malignant gallbladder (GB) polyps by comparing radiological methods, including abdominal ultrasonography (US) and computed tomography (CT) scanning, with postoperative pathology findings. METHODS: Fifty-nine patients underwent laparoscopic cholecystectomy for a GB polyp of around 10 mm. They were divided into two groups, one with cholesterol polyps and the other with non-cholesterol polyps. Clinical features such as gender, age, symptoms, size and number of polyps, the presence of a GB stone, the radiologically measured maximum diameter of the polyp by US and CT scanning, and the measurements of diameter from postoperative pathology were recorded for comparative analysis. RESULTS: Fifteen of the 41 cases with cholesterol polyps (36.6%) were detected with US but not CT scanning, whereas all 18 non-cholesterol polyps were observed using both methods. In the cholesterol polyp group, the maximum measured diameter of the polyp was smaller by CT scan than by US. Consequently, the discrepancy between those two scanning measurements was greater than for the non-cholesterol polyp group. CONCLUSION: The clinical signs indicative of a cholesterol polyp include: (1) a polyp observed by US but not observable by CT scanning, (2) a smaller diameter on the CT scan compared to US, and (3) a discrepancy in its maximum diameter between US and CT measurements. In addition, US and the CT scan had low accuracy in predicting the polyp diameter compared to that determined by postoperative pathology.

HER-2/neu amplification is an independent prognostic factor in gastric cancer.

The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth and is extensively homologous and related to the epidermal growth factor receptor. HER-2/neu protein expression has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease, and with a poor prognosis, and constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationship between the expression of HER-2/neu and the clinicopathological characteristics of tumors, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for gastric cancer patients. HER-2/neu overexpression and gene amplification was examined with semiquantitative standardized immunohistochemical staining, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) in 182 gastric cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Twenty-nine (15.9%) of 182 patients expressed the HER-2/neu protein by immunohistochemistry. HER-2/neu gene amplification was detected in seven patients by CISH and FISH. Intestinal-type cancers exhibited higher rates of HER-2/neu amplification than did diffuse-type cancers (P < 0.05). Tumors with HER-2/neu amplification were associated with poor mean survival rates (922 vs 3243 days) and 5-year survival rates (21.4% vs 63.0%; P < 0.05). Age, TNM stage, and amplification of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu amplification may constitute an independent prognostic factor in gastric cancer patients, and patients exhibiting HER-2/neu amplification might constitute potential candidates for new adjuvant therapies which involve the use of humanized monoclonal antibodies.

[Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori eradication].

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication. METHODS: 1) First-line eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen military men in Armed Forces Capital Hospital were treated with 7 days of levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid, levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole 20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2) Second-line eradication: A consecutive series of 59 patients who failed H. pylori eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital were randomized to two groups. Thirty patients were retreated with 7 days of bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid, metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients were retreated with levofloxacin-azithromycin combined triple therapy. Patient's compliance and tolerability were evaluated at the end of treatment. The status of H. pylori infection was assessed 8 weeks later then. The successful eradication of H. pylori was defined as negative results from histology and CLO test, or 13C-urea breath test. RESULTS: First-line eradication rate of levofloxacin-azithromycin triple therapy was lower than that of standard PPI-based triple therapy, but there was no statistically significant difference (70.6% vs. 80.3%, p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined triple therapy was significantly lower than that of bismuth-based quadruple therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all patients were more than 85%. Two of patients with levofloxacin-azithromycin combined triple therapy complained self-limiting side effects (mild dizziness; mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin combined triple therapy should not be recommended as the first-line or second-line H. pylori eradication regimen in Korea.

Protective effects of bovine colostrum on non-steroidal anti-inflammatory drug induced intestinal damage in rats.

The aim of this study was to examine whether bovine colostrum was able to prevent the NSAID induced small intestinal damage in animals. The animal model population of the study consisted of 4 groups: control group, diclofenac group, diclofenac with 10% low fat milk group and diclofenac with 5% colostrum group. The animals with milk or colostrum were fed with 10% low fat milk or 5% colostral solution for 5 days before the administration of diclofenac. Gut injuries were induced by administration of a single dose of diclofenac (100 mg/kg orally). Epithelial permeability values (24 hour urinary excretion of 51Cr-ethylenediaminetetraacetic acid [51Cr-EDTA]), enteric aerobic bacterial counts, serum biochemical profiles and pathologic findings of distal ileum were measured. Diclofenac caused a marked increase in the intestinal permeability, enteric bacterial numbers and intestinal villous damage, and enteric protein and albumin loss. Combined administration of bovine colostrum reduced the increase in intestinal permeability, enteric bacterial overgrowth, protein losing enteropathy and mucosal villous damage of the small intestine induced by diclofenac. Bovine colostrum may have a beneficial effect in prevention of NSAID induced small intestinal injuries.

[Clinical significance of HER-2/neu expression in colon cancer].

BACKGROUND/AIMS: The HER-2/neu protein is involved in normal cell proliferation and tissue growth because it is extensively homologous and related to epidermal growth factor receptor. As a prognostic marker, HER-2/neu is used to forecast the clinical course and poor outcome in breast cancer. As a predictive marker, HER-2/neu is used to predict the therapeutic response to adjuvant chemotherapy and endocrine therapy in breast cancer. In this study, we investigated the relationships between clinical and pathologic characteristics of tumor and prognosis according to the HER-2/neu expression in colon cancer. This study was conducted for the future introduction of Herceptin therapy for colon cancer patients. METHODS: Overexpression of HER-2/neu was examined by semiquantitative standardized immunohistochemical staining kit in 88 patients with colon cancer. The patients underwent curative surgery at the Kangbuk Samsung Hospital. RESULTS: Overexpression of HER-2/neu was detected in 11 (12.5%) of 88 patients. Tumors with positive HER-2/neu staining showed a tendency for higher rates of nodal metastasis and poor mean survival (1,646 +/- 269 vs 2,631 +/- 141 days) and 5-year survival (65.5% vs 78.9%). CONCLUSIONS: Tumors with positive HER-2/neu staining showed a tendency for higher rates for nodal metastasis and poor clinical survival rate.

[Fibrinolytic activities and their relations to esophageal variceal bleeding in patients with liver cirrhosis].

BACKGROUND/AIMS: Esophageal variceal bleeding in liver cirrhosis is a major complication and has high mortality rate. We tried to find fibrinolytic parameters, which correlated with variceal bleeding in cirrhotic patients. METHODS: We divided the cirrhotic patients into two groups: bleeding group (group A, n=15) and non-bleeding group (Group B, n=17). Fibrinolytic parameters (fibrinogen, D-dimer, plasminogen, tissue plasminogen activator [t-PA], fibrin degradation product [FDP], and plasminogen activator inhibitor type-1 [PAI-1]) were compared between two groups. In the group A, serial samplings were taken at the initial period, 3 days, 8 days, 15 days and 6 weeks after the bleeding onset. RESULTS: Plasma levels of FDP and D-dimer in the group A were significantly higher than the group B (1.7 +/- 1.16 vs. 0.95 +/- 1.27 mg/L and 10.96 +/- 6.58 vs. 4.99 +/- 3.50 micro gram/mL, respectively, p value<0.05). The clinical, biochemical, and coagulation parameters didn't show significant differences in both groups. The fibrinolytic parameters were improved along with the hemodynamic stabilization in group A. CONCLUSIONS: Cirrhotic patients with increased fibrinolytic activity were at higher risk of bleeding. Thus, the measurement of these parameters would be useful to identify patients at higher risk of esophageal variceal bleeding.

Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men.

BACKGROUND AND AIM: Although insulin resistance is often considered the link between obesity and non-alcoholic fatty liver disease (NAFLD), the role of insulin resistance, independent of obesity, as a NAFLD risk factor in non-obese men has been less well established. Systemic inflammation may be accompanied by insulin resistance in healthy subjects. The goal of the present study was to examine if insulin resistance and systemic inflammatory markers are independent predictors of NAFLD in non-obese men. METHODS: The authors conducted a cross-sectional survey of 120 patients with NAFLD and 240 controls matched by age and body mass index. Controls had no evidence of alcohol abuse, hepatitis B or C, obesity, or previous history of diabetes, fasting hyperglycemia or hypertension. Diagnosis of NAFLD was based on an elevated alanine aminotransferase level and sonographic evidence of a fatty liver. Insulin resistance was determined using a homeostasis model assessment (HOMA-IR). RESULTS: The age-adjusted risk of developing NAFLD was strongly associated with the elevated levels in measurements of uric acid, fasting blood sugar, triglycerides, apolipoprotein B, C-reactive protein (CRP) and HOMA-IR, and decreased levels of high density lipoprotein cholesterol and apolipoprotein A-I. Multivariate analysis based on univariate analysis indicated that an increase in CRP (odds ratio [OR] = 1.37; 95% confidence interval [CI]: 1.06-1.77) per 1 SD (1.48 mg/L) and HOMA-IR (OR = 2.28; 95% CI: 1.67-3.11) per 1 SD (0.63) were independent risk factors for NAFLD. CONCLUSION: Insulin resistance and systemic inflammatory response are of key importance for inducing NAFLD, particularly in apparently healthy non-obese men.

[Intestinal permeability in patients with viral and alcoholic liver disease].

BACKGROUND/AIMS: Increased intestinal permeability has been possible contributing factors to the pathogenesis of alcoholic liver disease. Moreover, it can contribute to the development of bacterial infection and intestinal endotoxemia in patients with liver cirrhosis. This study aimed to examine the difference of intestinal barrier dysfunction between alcoholic and viral liver disease patients through the comparison of the intestinal permeabilities of patients with clinical characteristics. METHODS: Intestinal permeabilities were measured in 18 healthy controls, 41 patients with alcoholic liver disease (17 cases of alcoholic liver disease without cirrhosis and 24 cases of alcoholic liver cirrhosis) and 46 patients with viral liver disease (14 cases of chronic viral hepatitis and 32 cases of viral liver cirrhosis) by measuring 24 hour urine excretion of 51Cr-EDTA. RESULTS: The intestinal permeability was significantly increased in the patients with alcoholic liver disease without cirrhosis (5.62 +/- 2.80%), alcoholic liver cirrhosis (5.29 +/- 2.48%) and viral liver cirrhosis (3.15 +/- 1.39%) compared with that in control subjects (1.99 +/- 0.53%). On the contrary, it was not increased in the patients with chronic viral hepatitis (2.05 +/- 0.57%) versus controls. The significant correlation was not found between intestinal permeability and clinical and laboratory findings. CONCLUSIONS: The intestinal permeability was elevated in patients with alcoholic liver disease compared to those with viral liver cirrhosis. The pathophysiology of liver injury secondary to intestinal epithelial damage may be different between alcoholic and viral liver diseases.