Development and roll out of the JETS e-portfolio: a web based electronic portfolio for endoscopists.

The JAG Endoscopy Training System (JETS) e-portfolio was designed to provide an electronic log of endoscopic experience, improve the effectiveness of training, streamline the JAG certification process and support the quality assurance of trainers, units and regional training programmes. It was piloted in 2008 with an 82.6% uptake in trainees offered the system. The system was released in the UK in September 2009. Steady adoption across the UK demonstrates the service finds it a valuable tool. In time it will be the only vehicle through which a trainee can achieve certification through JAG to practise independently.

Downstaging of colorectal cancer by the National Bowel Cancer Screening programme in England: first round data from the first centre.

OBJECTIVE: Data from randomized controlled trials of Colorectal Cancer (CRC) screening in Nottingham, UK and Funen, Denmark and pilot data from the English and Scottish arms of the National Bowel Cancer Screening Programme (NBCSP) have demonstrated predominantly early-stage disease amongst the screened population. The aim of this study was to investigate whether downstaging of cancers occurred in the NBCSP in Wolverhampton. METHOD: A case-control study was performed to compare the staging of CRC diagnosed in the NBCSP-screened population during the prevalent round (2 years) of screening, with cancers diagnosed prior to the introduction of the NBCSP. RESULTS: The total population in the screening area is 899 000. A total of 108 346 FOB kits were sent out of which 55 931 were returned (51.6% uptake), A total of 1039 colonoscopies were performed with a 94.75% unadjusted caecal intubation rate. There were three complications (haemorrhages 3) and no perforations. The NBCSP in Wolverhampton identified 106 (75% male) CRC in the first 2 years with 45.3% Dukes A, 21.7% B, 29.2% C and 3.8% D. Two hundred and fifty-six (61% male) CRC were identified in the control group, 10.1% Dukes A, 50.0% B, 36.3% C and 3.5% D. There was a highly significant shift towards earlier stage disease in the screened group (P < 0.0001). CONCLUSION: The 2-year data from the first English centre to start bowel cancer screening demonstrates significant downstaging of cancer, consistent with both the RCT and pilot data.

Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts.

Intestinal strictures are frequent in Crohn's disease but not ulcerative colitis. We investigated the expression of transforming growth factor (TGF)-beta isoforms by isolated and cultured primary human intestinal myofibroblasts and the responsiveness of these cells and intestinal epithelial cells to TGF-beta isoforms. Normal intestinal myofibroblasts released predominantly TGF-beta(3) and ulcerative colitis myofibroblasts expressed both TGF-beta(1) and TGF-beta(3), whereas in myofibroblast cultures from fibrotic Crohn's disease tissue, there was significantly lower expression of TGF-beta(3) but enhanced release of TGF-beta(2). These distinctive patterns of TGF-beta isoform release were sustained through several myofibroblast passages. Proliferation of Crohn's disease myofibroblasts was significantly greater than that of myofibroblasts derived from normal and ulcerative colitis tissue. In contrast to cells from normal and ulcerative colitis tissue, neutralization of the three TGF-beta isoforms did not affect the proliferation of Crohn's disease intestinal myofibroblasts. Studies on the effect of recombinant TGF-beta isoforms on epithelial restitution and proliferation suggest that TGF-beta(2) may be the least effective of the three isoforms in intestinal wound repair. In conclusion, the enhanced release of TGF-beta(2) but reduced expression of TGF-beta(3) by Crohn's disease intestinal myofibroblasts, together with their enhanced proliferative capacity, may lead to the development of intestinal strictures.

Human colonic subepithelial myofibroblasts modulate transepithelial resistance and secretory response.

The epithelium of the gastrointestinal tract transports ions and water but excludes luminal microorganisms and toxic molecules. The factors regulating these important functions are not fully understood. Intestinal myofibroblasts lie subjacent to the basement membrane, at the basal surface of epithelial cells. We recently showed that primary cultures of adult human colonic subepithelial myofibroblasts express cyclooxygenase (COX)-1 and COX-2 enzymes and release bioactive transforming growth factor-beta (TGF-beta). In this study we have investigated the role of normal human colonic subepithelial myofibroblasts in the regulation of transepithelial resistance and secretory response in HCA-7 and T84 colonic epithelial cell lines. Cocultures of epithelial cells-myofibroblasts and medium conditioned by myofibroblasts enhanced transepithelial resistance and delayed mannitol flux. A panspecific antibody to TGF-beta (but not piroxicam) antagonized this effect. In HCA-7 cells, myofibroblasts downregulated secretagogue-induced change in short-circuit current, and this effect was reversed by pretreatment of myofibroblasts with piroxicam. In contrast to HCA-7 cells, myofibroblasts upregulated the agonist-induced secretory response in T84 cells. This study shows that intestinal subepithelial myofibroblasts enhance barrier function and modulate electrogenic chloride secretion in epithelial cells. The enhancement of barrier function was mediated by TGF-beta. In contrast, the modulation of agonist-induced change in short-circuit current was mediated by cyclooxygenase products. These findings suggest that colonic myofibroblasts regulate important functions of epithelial cells via distinct secretory products.

Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta3.

After injury and loss of epithelial cells, intestinal barrier function is reestablished by migration of viable epithelial cells from the wound edge (restitution). Myofibroblasts are located close to the basal surface of epithelial cells. This study aimed to investigate the role of human colonic subepithelial myofibroblasts in epithelial restitution. Primary cultures of subepithelial myofibroblasts were established. Monolayers of the epithelial cell lines IEC-6 and T84 were "wounded" in a standard manner to create an in vitro model of restitution. Migration of epithelial cells across the wound edge was assessed following culture in myofibroblast-conditioned medium. Myofibroblast expression of transforming growth factor (TGF)-beta isoforms was examined using RT-PCR, and TGF-beta isoform bioactivity was assessed using Mv 1 Lu bioassay. Myofibroblast-conditioned medium, via a TGF-beta-dependent pathway, significantly enhanced migration of epithelial cells across the wound edge and significantly inhibited cell proliferation in wounded monolayers. Messenger RNA for TGF-beta1, -beta2, and -beta3 was detected in the myofibroblasts, and Mv 1 Lu bioassay showed the presence of predominantly bioactive TGF-beta3. This study shows that human colonic subepithelial myofibroblasts secrete predominantly bioactive TGF-beta3 and enhance restitution in wounded epithelial monolayers via a TGF-beta-dependent pathway.

Current pharmacotherapy for inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD), collectively termed inflammatory bowel disease (IBD), are chronic spontaneously relapsing enteropathies of unknown aetiology. Pharmacotherapy for IBD has essentially been unchanged for over twenty years, with therapy based around 5-aminosalicylic acid (5-ASA) preparations, corticosteroids, antibiotics and immunosuppression. Much of the controversy surrounding optimal use of these drugs in IBD arises as a consequence of methodological deficiencies in many of the early trials combined with the difficulty in consistent patient selection due to the heterogeneous nature of both UC and CD. More recently, well-designed clinical trials have attempted to provide an 'evidence based' approach to managing IBD which, in time, will allow optimisation of current therapies and accurate evaluation of novel agents. Over the past two decades, improved research methodology has considerably increased our molecular understanding of the aetiopathogenesis of IBD which has ultimately lead to the development of specific mediator directed or 'designer' drug therapy for IBD. This review evaluates the literature on current IBD therapy, summarises the important recent studies which have made an impact on clinical practice, and examines the risks and benefits of the novel agents which are currently under investigation in clinical trials of IBD therapy.

Novel approaches to inflammatory bowel disease.

Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease (IBD), are chronic, spontaneously relapsing disorders of unknown cause. These diseases appear to be immunologically mediated and have genetic and environmental influences. Although the cause of these diseases remains obscure, the pathogenesis of chronic intestinal inflammation is becoming clearer, due to improved animal models of enterocolitis and important advances in immunological techniques. Traditional therapy for IBD, although helping to induce and maintain disease remission, does little to alter the underlying fundamental disease process. New IBD therapy has not developed significantly over the past twenty years and includes 5-aminosalicylic acid preparations, corticosteroids and immunomodulatory agents, such as azathioprine, 6-mercaptopurine and methotrexate. There is, therefore, a need for new, specific disease-modifying therapy and the development of such therapy has been hastened by a greater understanding of the pathophysiology of IBD. This review examines the most recent novel therapies for IBD, with specific emphasis on immunomodulatory and novel anti-inflammatory therapies. Recent clinical trials are reviewed, and the potential advances and clinical impact that these novel agents may provide are discussed.