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The role of macrophage migration inhibitory factor (MIF) and autophagy in gastric cancer is not clear. We determined H. pylori infection status of the subjects and investigated the expression of MIF and autophagy markers (Atg5, LC3A and LC3B) in human gastric tissue at baseline. Then H. pylori eradication was done for H. pylori positive patients and MIF and Atg5 levels were investigated on each follow-up for both H. pylori-eradicated and H. pylori negative patients. Baseline tissue mRNA expression of MIF, Atg5, LC3A and LC3B was measured by real-time PCR in 453 patients (control 165, gastric dysplasia 82, and gastric cancer 206). Three hundred three patients (66.9%) had H. pylori infection at the time of enrollment. Only within H. pylori-positive group, MIF level was significantly elevated in patients with cancer than in control or dysplasia groups (P<0.05). LC3A and LC3B levels also showed significant differences within H. pylori-positive subgroups. H. pylori-positive dysplasia subgroup showed significantly lower (LC3A) (P<0.05) and higher (LC3B) mRNA levels (P<0.05) than in other subgroups. On follow-up, within H. pylori-eradicated group, Atg5 expression increased sequentially from control to dysplasia and cancer subgroups. Multiple linear regression showed autophagy markers (LC3A, LC3B, and Atg5) directly predicted MIF level (adjusted R2 = 0.492, P<0.001). Serial follow-up showed longitudinal increase in Atg5 level in general, with constantly higher levels in H. pylori-eradicated group than in -negative group. Intestinal metaplasia (IM) group initially showed higher Atg5 expression than the IM-negative group. However, it was reversed between the groups eventually because of the lower rate of increase in IM group. These results suggest a role of MIF and autophagy markers and their interaction in H. pylori-associated gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

There have been only a few reports investigating the clinical efficacy of follow-up endoscopy for detection of recurrent gastric cancer after total gastrectomy (TG). We reviewed the records of 747 patients undergoing TG from 2003 to 2012 and enrolled 267 patients (70 with early gastric cancer (EGC) and 197 with advanced gastric cancer (AGC)), who received one or more follow-up endoscopy and contrast abdominal computed tomography (CT) scan. We found no tumor recurrence in the 70 EGC patients during the mean follow-up periods of 42.1 ± 18 and 43.2 ± 19 months by endoscopy and contrast abdominal CT scan. In 197 AGC patients, 59 patients (29.8%) had confirmed tumor recurrence during mean follow-up periods of 40.5 ± 21 and 45.3 ± 22 months. The most common pattern of tumor recurrence was distant metastasis (n = 35) followed by peritoneal metastasis (n = 11). Among the other 13 cases with loco-regional recurrence, seven cases were regional lymph node metastases, four were anastomosis site recurrences, and two were duodenal stump and jejunal loop site recurrences. Three of the four cases of anastomosis site recurrence were found by both endoscopy and contrast abdominal CT scan; one case was missed by contrast abdominal CT scan. However, the two cases with duodenal stump and jejunal loop recurrences were detected by contrast abdominal CT scan only. An annual follow-up endoscopy for gastric cancer after TG might have a limited role in the detection of tumor recurrence, especially in patients with EGC. Contrast abdominal CT scan may be sufficient as a follow-up method for recurrent gastric cancer after TG. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic findings of low-volume alcohol consumption in relation to gastrointestinal cancers including gastric cancer are inconsistent. Methods: The association between alcohol intake and esophageal, gastric and colorectal cancer risk was examined in a population-based prospective cohort of 23,323,730 adults in Korea who had undergone a biennial evaluation provided by the National Health Insurance Corporation between the years 2009 and 2012. After median 5.4 years of follow-up, 9,171 esophageal, 135,382 gastric and 154,970 colorectal cancer cases were identified. Cox regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Light drinking as well as moderate to heavy alcohol consumption significantly increased the risks of the three gastrointestinal cancers (HR 1.51; 95% CI, 1.43–1.60; HR 1.08; 95% CI, 1.06–1.09; HR 1.12; 95% CI, 1.11–1.14) compared with non-drinkers after adjusting for age, sex, smoking, exercise, income, body mass index, and diabetes. The synergistically increased cancer risk between excessive amount of alcohol consumption and currently smoking or underweight individuals was observed only in the esophageal cancers. Conclusions: Light drinking including even one alcoholic drink a day is associated with increased risks of esophageal, gastric and colorectal cancer. [ABSTRACT FROM AUTHOR]

Gamma-glutamyltransferase (GGT) is a marker for hepatic injury and alcohol consumption. However, the association of GGT with the risk of oesophageal carcinoma (OC) has not been fully recognized to date. Therefore, this study aimed to determine the association between elevated GGT and OC, by also considering the body mass index (BMI) of the subjects. Clinical data from 8,388,256 Korean individuals, who were aged 40 years and over and who received healthcare check-ups arranged by the national insurance program in 2007 and 2008, were analysed. Newly diagnosed OC was identified using claims data during a median follow-up duration of 8.72 years. During the study period, 6,863 individuals (0.08%) developed OC. We found that there was an increased risk of OC in subjects with serum GGT values >18 IU/L. Furthermore, a BMI <18.5 kg/m2 (underweight) was associated with increased OC risk, while a BMI ≥23.0 kg/m2 was associated with a reduced OC risk. Individuals who were both underweight and in the highest GGT quartile (≥40 IU/L) had a far greater risk of OC compared to other individuals (hazard ratio: 3.65, 95% confidence interval: 3.10–4.30). In conclusion, increased serum GGT was associated with an increased risk of developing OC in the general Korean population, regardless of age, sex, smoker status, or alcohol consumption. [ABSTRACT FROM AUTHOR]

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance. [ABSTRACT FROM AUTHOR]

Epidemiological data indicate that type 2 diabetes is associated with increased risk of hepatocellular carcinoma (HCC). However, risk stratification for HCC has not been fully elucidated in diabetic population. The aim of this study was to identify potential predictors of HCC in diabetic patients without chronic viral hepatitis. A cohort of 3,544 diabetic patients without chronic viral hepatitis or alcoholic cirrhosis was established and subjects were randomly allocated into a derivation and a validation set. A scoring system was developed by using potential predictors of increased risk of HCC from the Cox proportional hazards model. The performance of the scoring system was tested for validation by using receiver operating characteristics analysis. During median follow-up of 55 months, 36 cases of HCC developed (190 per 100,000 person-years). The 5- and 10-year cumulative incidences of HCC were 1.0%, and 2.2%, respectively. Multivariate Cox regression analysis showed that age > 65 years, low triglyceride levels and high gamma-glutamyl transferase levels were independently associated with an increased risk of HCC. DM-HCC risk score, a weighted sum of scores from these 3 parameters, predicted 10-year development of HCC with area under the receiver operating characteristics curve of 0.86, and discriminated different risk categories for HCC in the derivation and validation cohort. In conclusion, old age, low triglyceride level and high gamma-glutamyl transferase level may help to identify individuals at high risk of developing HCC in diabetic patients without chronic viral hepatitis or alcoholic cirrhosis. [ABSTRACT FROM AUTHOR]