Explore the vast range of titles available.

Objective To evaluate the benefit of mass eradication of Helicobacter pylori infection in reducing premalignant gastric lesions. Design Mass eradication of H pylori infection was started from 2004 for a Taiwanese population with prevalent H pylori infection, who were >30 years of age. Participants positive for the 13C-urea breath test underwent endoscopic screening and 1-week clarithromycin-based triple therapy. For subjects whose initial treatment failed, 10-day levofloxacin-based triple therapy was administered. The main outcome measures were changes in the prevalence of H pylori infection and premalignant gastric lesions, and changes in the incidence of premalignant gastric lesions and gastric cancer before (1995–2003) and after (2004–2008) chemoprevention using various comparators. Results The reduction in H pylori infection was 78.7% (95% CI 76.8% to 80.7%), and the estimated incidence of re-infection/recrudescence was 1% (95% CI 0.6% to 1.4%) per person-year. The effectiveness of reducing the incidence of gastric atrophy resulting from chemoprevention was significant at 77.2% (95% CI 72.3% to 81.2%), while the reduction in intestinal metaplasia was not significant. Compared with the 5-year period before chemoprevention and in the absence of endoscopic screening, the effectiveness in reducing gastric cancer incidence during the chemoprevention period was 25% (rate ratio 0.753, 95% CI 0.372 to 1.524). The reduction in peptic ulcer disease was 67.4% (95% CI 52.2% to 77.8%), while the incidence of oesophagitis was 6% (95% CI 5.1% to 6.9%) after treatment. Conclusions Population-based eradication of H pylori infection has led to a significant reduction in gastric atrophy at the expense of increased oesophagitis. The ultimate benefit in reducing gastric cancer incidence and its mortality should be validated by a further long-term follow-up. Trial registration number NCT00155389.

Objective Type 2 diabetes mellitus is associated with a higher risk of hepatocellular carcinoma (HCC), which is attenuated by the use of metformin. However, there are no studies addressing the effect of metformin on hepatocarcinoma cells from the antitumoural perspective. Design In the nationwide case-control study, the authors recruited 97 430 HCC patients and 194 860 age-, gender- and physician visit date-matched controls. The chemopreventive effects of metformin were examined by multivariate analysis and stratified analysis. The in vitro effects of metformin on cell proliferation and cell cycle were studied in HepG2 and Hep3B hepatoma cell lines. Results The OR of diabetes in HCC patients was 2.29 (95% CI 2.25 to 2.35, p<0.001). Each incremental year increase in metformin use resulted in 7% reduction in the risk of HCC in diabetic patients (adjusted OR=0.93, 95% CI 0.91 to 0.94, p<0.0001). In the multivariate stratified analysis, metformin use was associated with a reduced risk of HCC in diabetic patients in nearly all subgroups. Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Combined treatment of oral metformin with doxorubicin functioned more efficiently than either agent alone, in vivo. Conclusions Use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner, via inhibition of hepatoma cells proliferation and induction of cell cycle arrest at G0/G1 phase.

Objective Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this study we evaluated the utility of detecting mutant DNA in secretin-stimulated pancreatic juice. Design Secretin-stimulated pancreatic juice was collected from the duodenum of 291 subjects enrolled in Cancer of the Pancreas Screening trials at five US academic medical centres. The study population included subjects with a familial predisposition to pancreatic cancer who underwent pancreatic screening, and disease controls with normal pancreata, chronic pancreatitis, sporadic intraductal papillary mucinous neoplasm (IPMN) or other neoplasms. Somatic GNAS mutations (reported prevalence ∼66% of IPMNs) were measured using digital high-resolution melt-curve analysis and pyrosequencing. Results GNAS mutations were detected in secretin-stimulated pancreatic juice samples of 50 of 78 familial and sporadic cases of IPMN(s) (64.1%), 15 of 33 (45.5%) with only diminutive cysts (<5 mm), but none of 57 disease controls. GNAS mutations were also detected in five of 123 screened subjects without a pancreatic cyst. Among 97 subjects who had serial pancreatic evaluations, GNAS mutations detected in baseline juice samples predicted subsequent emergence or increasing size of pancreatic cysts. Conclusion Duodenal collections of secretin-stimulated pancreatic juice from patients with IPMNs have a similar prevalence of mutant GNAS to primary IPMNs, indicating that these samples are an excellent source of mutant DNA from the pancreas. The detection of GNAS mutations before an IPMN is visible suggests that analysis of pancreatic juice has the potential to help in the risk stratification and surveillance of patients undergoing pancreatic screening.

AimsSeveral microarray studies have reported microRNA (miRNA) expression signatures that classify cancer patients into different prognostic groups. No study has evaluated the association between miRNA expression patterns and gastric cancer prognosis. In this study, we developed a seven-miRNA signature that is closely associated with survival of patients with gastric cancer.Patients and methodsMiRNA expression profile was analysed by real-time RT-PCR in 100 gastric cancer patients, which were randomly assigned to either the training set or the testing set. Cox proportional hazard regression and risk-score analysis were used to identify a stage-independent set of seven-miRNA signature in the training set that could classify patients with significantly different prognosis. This miRNA signature was further validated by the testing set and an independent cohort 60 patients.ResultsWe have identified a seven-miRNA signature (miR-10b, miR-21, miR-223, miR-338, let-7a, miR-30a-5p, miR-126) for overall survival (p=0.0009) and relapse-free survival (p=0.0005) of gastric cancer patients. Multivariate analysis shown that the risk signature was an independent predictor of overall survival (HR=3.046; 95% CI, 1.246 to 7.445, p=0.015) and relapse-free survival (HR=3.337; 95% CI, 1.298 to 8.580, p=0.012). Furthermore, the predictive value of this seven-miRNA signature was validated in the testing set of 50 patients and an independent set of 60 patients.ConclusionOur seven-miRNA signature is closely associated with relapse-free and overall survival among patients with gastric cancer. The prognostic signature could be applicable to future decisions concerning treatment.

Background Many medical conditions are thought to cause gastroduodenal ulceration or erosion (GUE) in dogs. However, evidence for the association between many of these conditions and GUE in dogs is lacking. Objective To identify medical conditions associated with GUE in dogs. Animals One hundred and sixty‐eight dogs with GUE and 168 randomly selected control dogs without evidence of GUE identified on necropsy between January 2008 and September 2018. Methods Patient signalment, blood urea nitrogen (BUN) and serum creatinine concentrations, recently administered ulcerogenic drugs, as well as necropsy findings were recorded. The association between these findings and presence of GUE was assessed by univariable and multivariable analysis. Results In the final multivariable model, the following factors were associated with GUE: Nonsteroidal anti‐inflammatory drug (NSAID) administration (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.3‐17.4; P = .0004), glucocorticoid administration (OR, 3.0; 95% CI, 1.5‐5.9; P = .001), gastrointestinal neoplasia (OR, 13.5; 95% CI, 1.7‐108.0; P = .01) and gastrointestinal mechanical disease (foreign bodies, gastric dilatation, and volvulus; OR, 4.8; 95% CI, 1.2‐19.7; P = .03). Additionally, working dog breeds were predisposed to GUE compared to mixed breed dogs (OR, 2.8; 95% CI, 1.1‐7.4; P = .04). Insufficient clinical data was available to either support or refute a role of other putative risk factors evaluated. Conclusion and Clinical Importance Administration of NSAID or glucocorticoid and gastrointestinal neoplasia or mechanical disease were associated with GUE in dogs. The potential predisposition of working breed dogs for GUE requires further investigation.

BackgroundBetween 2000 and 2007, a demonstration pilot of biennial guaiac faecal occult blood test (GFOBT) screening was carried out in Scotland.MethodsInterval cancers were defined as cancers diagnosed within 2 years (ie, a complete screening round) of a negative GFOBT. The stage and outcome of the interval cancers were compared with those arising contemporaneously in the non-screened Scottish population. In addition, the gender and site distributions of the interval cancers were compared with those in the screen-detected group and the non-screened population.ResultsOf the cancers diagnosed in the screened population, interval cancers comprised 31.2% in the first round, 47.7% in the second, and 58.9% in the third, although this was due to a decline in the numbers of screen-detected cancers rather than an increase in interval cancers. There were no consistent differences in the stage distribution of interval cancers and cancers from the non-screened population, and, in all three rounds, both overall and cancer-specific survival were significantly better for patients diagnosed with interval cancers (p<0.01). The percentage of cancers arising in women was significantly higher in the interval cancer group (50.2%) than in either the screen-detected group (35.3%, p<0.001) or the non-screened group (40.6%, p<0.001). In addition, the proportion of both right-sided and rectal cancers was significantly higher in the interval cancer group than in either the screen-detected (p<0.001) or non-screened (p<0.004) groups.ConclusionsAlthough GFOBT screening is associated with substantial interval cancer rates that increase with screening round, the absolute numbers do not. Interval cancers are associated with a better prognosis than cancers arising in a non-screened population, and GFOBT appears to preferentially detect cancers in men and the left side of the colon at the expense of cancers in women and in the right colon and rectum.

Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. Design Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. Results The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10−16), confirmed in external validation sets (Sweden p=1.2×10−6, Finland p=2×10−5). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Conclusion Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.

BackgroundGastrointestinal (GI) lymphomas comprise a group of distinct clinicopathological entities of B- or T- cell type, with primary gastrointestinal Hodgkin lymphoma being extremely uncommon. The GI tract is the predominant site of extranodal non-Hodgkin lymphoma accounting for 30–40% of all extranodal lymphomas. In the Western world, the stomach is the most commonly involved site followed by the small bowel. Several chronic inflammatory and immune-mediated disorders which predispose to accelerated cell turnover may lead to the malignant transformation of gut lymphocytes and ultimately manifest as GI lymphoma. The challenge for the clinical gastroenterologist is that these tumors may have varied presentations, ranging from nonspecific symptoms such as dyspepsia or bloating to abdominal pain, nausea, vomiting, GI bleeding, diarrhea, weight loss or bowel obstruction.ObjectiveWe illustrate the range of presentations of GI lymphoma with examples based on consecutive cases evaluated at our institution over a 6-month period. These cases demonstrate how appropriately directed endoscopic evaluation with biopsies has the potential to provide a definitive diagnosis and allow the patient to proceed to definitive therapy.ConclusionsThe GI tract is the most commonly involved site for extranodal lymphoma with the stomach being most frequently involved organ.Chronic Helicobacter pylori infection, celiac disease, inflammatory bowel disease and autoimmune disorders may predispose to GI lymphoma. This heterogenous group of diseases has varied presentations that may mimic several other GI clinico-pathologic entities. GI lymphomas may be diagnosed with appropriately directed endoscopic evaluation coupled with generous tissue sampling and expert pathologic assessment. Management may range from antibiotic therapy, in the case of Helicobacter pylori-associated gastric MALT lymphoma, to chemotherapy with or without radiation and, in rare instances, surgery. There are presently no guidelines to direct endoscopic surveillance of GI lymphomas following treatment.