Background-The cytokines interleukin 1 (IL-1 ) and tumour necrosis factor (TNF-) are inhibitors of gastric acid secretion when administered systemically. Aims-To investigate the inhibitory eVect of IL-1 and TNF-on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition. Methods-Rabbit parietal cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation. Results-IL-1 and TNF-inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal eVects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no eVect on stimulation by dibutyrylcAMP. Inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H 2 or gastrin/CCK B receptors. Pertussis toxin abolished the inhibitory eVects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory eVects of TNF-against all stimuli but only reduced the eVects of IL-1 against histamine and forskolin stimulation. Conclusions-IL-1 and TNF-seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion. (Gut 1998;42:227-234)

Obesity is an important risk factor for esophageal adenocarcinoma (EAC), and elevated serum leptin is characteristic of obesity. We hypothesized that leptin may have biological effects in promoting esophageal adenocarcinoma and examined the effects of leptin on the OE33 Barrett's-derived EAC line. Proliferation was assessed by dimethylthiazoldiphenyltetra-zoliumbromide and 5-bromo-2'-deoxyuridine incorporation assays and apoptosis by ELISA of intracellular nucleosomes. Intracellular signaling was examined using specific pharmacological inhibitors and direct detection of phosphorylated active kinases. Expression of the long and short leptin receptors by OE33 cells was confirmed by RT-PCR, Western blotting and immunocytochemistry. Leptin stimulated OE33 cell proliferation in a dose-dependent manner and inhibited apoptosis. These effects were dependent on cyclooxygenase (COX)-2 and replicated by adding prostaglandin E2 (PGE2). The effects of PGE2 and leptin were abolished by the EP-4 antagonist AH23848. ERK, p38 MAPK, phosphatidylinositol 3'-kinase/Akt, and Janus tyrosine kinase (JAK)-2 were activated upstream of COX-2 induction, whereas the epidermal growth factor receptor and c-Jun NH2-terminal kinase (JNK) were downstream of COX-2. The activation of ERK and Akt but not p38 MAPK was JAK2 dependent. PGE2 stimulated phosphorylation of JNK in an EGF receptor-dependent manner, and activation of the epidermal growth factor receptor required protein kinase C, src, and matrix metalloproteinase activities. We conclude that leptin stimulates cell proliferation and inhibits apoptosis in OAC cells via ERK, p38 MAPK, phosphatidylinositol 3'-kinase/Akt, and JAK2-dependent activation of COX-2 and PGE2 production. Subsequent PGE2-mediated transactivation of the epidermal growth factor receptor and JNK activation are essential to the leptin effects. These effects may contribute to the greatly increased risk of esophageal adenocarcinoma in obesity.

Iron deficiency anaemia (IDA) is a major cause of morbidity and burden of disease worldwide. It can generally be diagnosed by blood testing and remedied by iron replacement therapy (IRT) using the oral or intravenous route. The many causes of iron deficiency include poor dietary intake and malabsorption of dietary iron, as well as a number of significant gastrointestinal (GI) pathologies. Because blood is iron-rich it can result from chronic blood loss, and this is a common mechanism underlying the development of IDA—for example, as a consequence of menstrual or GI blood loss.Approximately a third of men and postmenopausal women presenting with IDA have an underlying pathological abnormality, most commonly in the GI tract. Therefore optimal management of IDA requires IRT in combination with appropriate investigation to establish the underlying cause. Unexplained IDA in all at-risk individuals is an accepted indication for fast-track secondary care referral in the UK because GI malignancies can present in this way, often in the absence of specific symptoms. Bidirectional GI endoscopy is the standard diagnostic approach to examination of the upper and lower GI tract, though radiological scanning is an alternative in some situations for assessing the large bowel. In recurrent or refractory IDA, wireless capsule endoscopy plays an important role in assessment of the small bowel.IDA may present in primary care or across a range of specialties in secondary care, and because of this and the insidious nature of the condition it has not always been optimally managed despite the considerable burden of disease— with investigation sometimes being inappropriate, incorrectly timed or incomplete, and the role of IRT for symptom relief neglected. It is therefore important that contemporary guidelines for the management of IDA are available to all clinicians. This document is a revision of previous British Society of Gastroenterology guidelines, updated in the light of subsequent evidence and developments.

Background: Many Helicobacter pylori eradication regimens have been described. There are little data reporting their efficacy or integration in routine clinical practice. The overall results of eradication therapy in a cohort of patients are described and an algorithm for management outlined.

Obesity increases the risk of developing several cancers including oesophageal adenocarcinoma (OAC). Obesity is characterized by hyperleptinaemia and hypoadiponectinaemia: we have hypothesized that these hormonal factors may contribute to the progression of OAC. We have examined the effects of leptin and adiponectin on proliferation of OAC cells. Leptin stimulated proliferation in 4 different OAC lines (OE33, OE19, BIC-1 and FLO) and this was inhibited by globular but not full length adiponectin. All 4 OAC lines expressed both adiponectin-receptor isoforms (AdipoR1 and AdipoR2).

Abstract:The incidence of oesophageal adenocarcinoma has increased dramatically in the developed world in the last half century. Over approximately the same period there has been an increase in the prevalence of obesity. Multiple epidemiological studies and metaanalyses have confirmed that obesity, especially abdominal, visceral obesity, is a risk factor for gastro-oesophageal reflux, Barrett's oesophagus and oesophageal adenocarcinoma. Although visceral obesity enhances gastro-oesophageal reflux, the available data also show that visceral obesity increases the risk of Barrett's oesophagus and adenocarcinoma via reflux-independent mechanisms. Several possible mechanisms could link obesity with the risk of oesophageal adenocarcinoma in addition to mechanical effects increasing reflux. These include reduced gastric Helicobacter pylori infection, altered intestinal microbiome, factors related to lifestyle, the metabolic syndrome and associated low-grade inflammation induced by obesity and the secretion of mediators by adipocytes which may directly influence the oesophageal epithelium. Of these adipocyte-derived mediators, increased leptin levels have been independently associated with progression to oesophageal adenocarcinoma and in laboratory studies leptin enhances malignant behaviours in cell lines. Adiponectin is also secreted by adipocytes and levels decline with obesity: decreased serum adiponectin levels are associated with malignant progression in Barrett's oesophagus and experimentally adiponectin exerts anticancer effects in Barrett's cell lines and inhibits growth factor signalling. At present there are no proven chemopreventative interventions that may reduce the incidence of obesity-associated oesophageal cancer: observational studies suggest that the combined use of a statin and aspirin or another cyclo-oxygenase inhibitor is associated with a significantly reduced cancer incidence in patients with Barrett's oesophagus.

Endoscopy assessors applied a greater range of scores using the new DOPS scale based on degree of supervision in two cohorts of trainees matched for experience. Our study provides construct validity evidence in support of the new scale format.

Introduction In the UK, endoscopy certification is administered by the Joint Advisory Group on Gastrointestinal Endoscopy (JAG). Since 2011, certification for upper and lower gastrointestinal endoscopy has been awarded via a national (JETS) e-portfolio to the main training specialties of: gastroenterology, gastrointestinal surgeons (GS) and non-medical endoscopists (NME). Trends in endoscopy certification and differences between trainee specialties were analyzed. Methods This prospective UK-wide observational study identified trainees awarded gastroscopy, sigmoidoscopy, colonoscopy (provisional and full) certification between June 2011 – 2017. Trends in certification, procedures and time-to-certification, and key performance indicators (KPIs) in the 3-month pre- and post-certification period were compared between the three main training specialties. Results Three thousand one hundred fifty-seven endoscopy-related certifications were awarded to 1928 trainees from gastroenterology (52.3 %), GS (28.4 %) and NME (16.5  %) specialties. During the study period, certification numbers increased for all modalities and specialties, particularly NME trainees. For gastroscopy and colonoscopy, procedures-to-certification were lowest for GS (P < 0.001), whereas time-to-certification was consistently shortest in NMEs (P < 0.001). A post-certification reduction in mean cecal intubation rate (95.2 % to 93.8 %, P < 0.001) was observed in colonoscopy, and D2 intubation (97.6 % to 96.2 %, P < 0.001) and J-maneuver (97.3 % to 95.8 %, P < 0.001) in gastroscopy. Overall, average pre- and post-certification KPIs still exceeded national minimum standards. There was an increase in PDR for NMEs after provisional colonoscopy certification but a decrease in PDR for GS trainees after sigmoidoscopy and full colonoscopy certification. Conclusion Despite variations among trainee specialties, average pre- and post-certification KPIs for certified trainees met national standards, suggesting that JAG certification is a transparent benchmark which adequately safeguards competency in endoscopy training.