Genome-wide analysis of barrett's adenocarcinoma. a first step towards identifying patients at risk and developing therapeutic paths

BACKGROUND: Barrett's esophagus metaplasia is the key precursor lesion of esophageal adenocarcinoma. The aim of this study was to find a subset of markers that may allow the identification of patients at risk for esophageal adenocarcinoma, and to determine genes differentially expressed in esophageal squamous cell carcinoma. METHODS:Laser capture microdissection technique was applied to procure cells from defined regions. Genome-wide RNA profiling was performed on esophageal adenocarcinoma (n = 21), Barrett's esophagus (n = 20), esophageal squamous carcinoma (n = 9) and healthy esophageal biopsies (n = 18) using the Affymetrix Human Genome U133plus 2.0 array. Microarray results were validated by quantitative real-time polymerase chain reaction in a second and independent cohort and by immunohistochemistry of two putative markers in a third independent cohort. RESULTS:Through unsupervised hierarchical clustering and principal component analysis, samples were separated into four distinct groups that match perfectly with histology. Many genes down-regulated in esophageal cancers belong to the epidermal differentiation complex or the related GO-group "cornified envelope" of terminally differentiated keratinocytes. Similarly, retinol metabolism was strongly down-regulated. Genes showing strong overexpression in esophageal carcinomas belong to the GO groups extracellular region /matrix such as MMP1, CTHRC1, and INHBA. According to an analysis of genes strongly up-regulated in both esophageal adenocarcinoma and Barrett's esophagus, REG4 might be of particular interest as an early marker for esophageal adenocarcinoma. CONCLUSIONS:Our study provides high quality data, which could serve for identification of potential biomarkers of Barrett's esophagus at risk of esophageal adenocarcinoma progression

Leukotriene receptor expression in esophageal squamous cell cancer and non-transformed esophageal epithelium: a matched case control study

Study questionnaire. (DOC 21 kb

DNA methylation in human gastric epithelial cells defines regional identity without restricting lineage plasticity

BACKGROUND: Epigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronic Helicobacter pylori infections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail. RESULTS: Here, we establish gastric mucosa derived primary cell cultures as a reliable source of native human epithelium. We describe the DNA methylation landscape across the phenotypically different regions of the healthy human stomach, i.e., antrum, corpus, fundus together with the corresponding transcriptomes. We show that stable regional DNA methylation differences translate to a limited extent into regulation of the transcriptomic phenotype, indicating a largely permissive epigenetic regulation. We identify a small number of transcription factors with novel region-specific activity and likely epigenetic impact in the stomach, including GATA4, IRX5, IRX2, PDX1 and CDX2. Detailed analysis of the Wnt pathway reveals differential regulation along the craniocaudal axis, which involves non-canonical Wnt signaling in determining cell fate in the proximal stomach. By extending our analysis to pre-neoplastic lesions and gastric cancers, we conclude that epigenetic dysregulation characterizes intestinal metaplasia as a founding basis for functional changes in gastric cancer. We present insights into the dynamics of DNA methylation across anatomical regions of the healthy stomach and patterns of its change in disease. Finally, our study provides a well-defined resource of regional stomach transcription and epigenetics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01406-4

The Effect of Oral Pancreatic Enzyme Supplementation on the Course and Outcome of Acute Pancreatitis: A Randomized, Double-Blind Parallel-Group Study

Context Pancreatic exocrine insufficiency is a significant problem after acute pancreatitis. Objective To evaluate whether oral pancreatic enzyme supplementation improves the recovery of pancreatic exocrine function and to explore the efficacy, safety and tolerability of pancreatic enzyme supplementation in patients during the refeeding period after acute pancreatitis. Design Prospective double-blind, placebo controlled, randomized study. Patients The sudy included 56 patients with acute pancreatitis. Main outcome measures Primary efficacy variable was recovery from pancreatic exocrine insufficiency. Secondary objectives were body weight, abdominal pain, course of APACHE II score, patient’s symptoms and quality of life. Results Twenty of the 56 patients showed low fecal elastase values indicating pancreatic exocrine insufficiency after acute pancreatitis. Median time to recovery from exocrine pancreatic insufficiency was 14 days in the enzyme supplementation group and 23 days in the placebo group but overall differences for primary and all but one secondary endpoint did not reach statistical significance. However, a positive tendency in favour of enzyme supplementation was found for quality of life parameters (FACT-Pa) in all subscores. There were no relevant differences between placebo and oral pancreatic enzyme supplementation detected with respect to safety and tolerability. Conclusion Enzyme supplementation positively effects the course of acute pancreatitis if administered during the early refeeding phase after acute pancreatitis. There is evidence that oral pancreatic enzyme supplementation has a positive impact on the course of the disease and the global health status (less weight loss, less flatulence, improved quality of life). Oral pancreatic enzyme supplementation was safely administered and can be added to the treatment regimen of patients in a refeeding status after severe acute pancreatitis.Image: Kaplan-Meier estimates of the proportion of subjects with a response (Figure 2

DPO multiplex PCR as an alternative to culture and susceptibility testing to detect Helicobacter pylori and its resistance to clarithromycin

<p>Abstract</p> <p>Background</p> <p>Macrolide resistance in <it>Helicobacter pylori </it>is the major risk factor for treatment failure when using a proton pump inhibitor-clarithromycin containing therapy. Macrolide resistance is due to a few mutations on the 23S ribomosal subunit encoded by the 23S rRNA gene. The present study aimed at investigating the performance of the dual priming oligonucleotide (DPO)-PCR kit named Seeplex^®ClaR-<it>H. pylori </it>ACE detection designed to detect <it>H. pylori </it>and two types of point mutations causing clarithromycin resistance in <it>H. pylori</it>.</p> <p>Methods</p> <p>The performance of Seeplex^®ClaR-<it>H. pylori </it>ACE detection was evaluated on 127 gastric biopsies in comparison to conventional bacterial culture followed by the determination of susceptibility to clarithromycin by E-test, as well as by an in-house real-time PCR using a fluorescence resonance energy transfer (FRET) technology.</p> <p>Results</p> <p>Considering culture as the reference test, the sensitivity of DPO-PCR and real-time FRET-PCR was 97.7% and 100% while specificity was 83.1% and 80.7%, respectively. However, both PCR were concordant in detecting 14 <it>H. pylori </it>positive cases which were negative by culture. Globally, E-test and DPO-PCR were concordant with regard to clarithromycin susceptibility in 95.3% of the cases (41/43), while real-time FRET-PCR and DPO-PCR were concordant in 95% (57/60).</p> <p>Conclusion</p> <p>The DPO-PCR is an interesting tool to detect <it>H. pylori </it>on gastric biopsies and to study its susceptibility to clarithromycin in laboratories that cannot perform real-time PCR assays.</p

o 029the impact of combining selective internal radiation therapy sirt with sorafenib on overall survival in patients with advanced hepatocellular carcinoma the soramic trial palliative cohort

n/

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study

Objectives: This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. Design: A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. Results: In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74–1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43–0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5–3.0). Conclusion: Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925