Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease.

Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7µm particle size reversed-phase C18 LC column at a flow rate of 200µL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups.

The incidence and aetiology of acute pancreatitis across Europe.

BACKGROUND: Acute pancreatitis is increasingly one of the most important acute gastrointestinal conditions throughout much of the world, although incidence and aetiology varies across countries and regions. This study investigated regional and national patterns in the incidence and aetiology of acute pancreatitis, demographic patterns in incidence and trends over time in incidence across Europe. METHODS: A structured review of acute pancreatitis incidence and aetiology from studies of hospitalised patient case series, cohort studies or other population based studies from 1989 to 2015 and a review of trends in incidence from 1970 to 2015 across all 51 European states. RESULTS: The incidence of acute pancreatitis was reported from 17 countries across Europe and ranged from 4.6 to 100 per 100 000 population. Incidence was usually highest in eastern or northern Europe, although reported rates often varied according to case ascertainment criteria. Of 20 studies that reported on trends in incidence, all but three show percentage increases over time (overall median increase = 3.4% per annum; range = -0.4%-73%). The highest ratios of gallstone to alcohol aetiologies were identified in southern Europe (Greece, Turkey, Italy and Croatia) with lowest ratios mainly in eastern Europe (Latvia, Finland, Romania, Hungary, Russia and Lithuania). CONCLUSIONS: The incidence of acute pancreatitis varies across Europe. Gallstone is the dominant aetiology in southern Europe and alcohol in eastern Europe with intermediate ratios in northern and western Europe. Acute pancreatitis continues to increase throughout most of Europe.

Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization.

OBJECTIVES: Barrett's oesophagus is a pre-neoplastic lesion, which develops as a complication of chronic gastro-oesophageal reflux disease and predisposes the patient to oesophageal adenocarcinoma. Our aim was to characterize karyotypic changes that may occur during the progression of Barrett's metaplasia through low-grade dysplasia and high-grade dysplasia to adenocarcinoma. METHODS: The technique of comparative genomic hybridization was used to characterize genome-wide changes in biopsies from patients with low-grade dysplasia, low-grade dysplasia plus high-grade dysplasia, high-grade dysplasia or adenocarcinoma. Both fresh and archival material was examined. RESULTS: Comparative genomic hybridization revealed a large amount of widespread chromosome instability at the high-grade dysplasia stage. No significant chromosome changes were detectable by comparative genomic hybridization in patients with low-grade dysplasia. Karyotypic changes in the adenocarcinoma patients were more specific than those found in the high-grade dysplasia patients. Chromosome 4 was amplified most often in high-grade dysplasia and chromosome 8q was amplified most frequently in the adenocarcinomas. CONCLUSIONS: These data demonstrate that high-grade dysplasia is the stage exhibiting widespread chromosome instability, which is detectable by comparative genomic hybridization. This instability is undetectable in low-grade dysplasia. The chromosome variation seen at high-grade dysplasia may be the source of more specific karyotypes that progress to adenocarcinoma. Importantly, we have identified chromosome 4 amplification as being heavily involved in the initiation of Barrett's progression. Specific chromosome changes (4 and 8q) may represent important regions on which to focus attention in future studies, with a view to identifying diagnostic markers.