Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%). Several IMs exhibited hypermethylation at DNA methylation valleys; however, IMs generally lack intragenic hypomethylation signatures of advanced malignancy. IM patients with shortened telomeres and chromosomal alterations were associated with subsequent dysplasia or GC; conversely patients exhibiting normal-like epigenomic patterns were associated with regression.

SUMMARYBackground: Many non-responders to azathioprine or mercaptopurine (6-mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6-methylmercaptopurine instead of the active 6-tioguanine (6-tioguanine) metabolites. Aim: To describe the use of allopurinol in mercaptopurine/azathioprine non-responders to deliberately shunt metabolism of mercaptopurine towards 6-tioguanine. Methods: Fifteen thiopurine non-responders whose metabolites demonstrated preferential metabolism towards 6-methylmercaptopurine are described. Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to

Until recently, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-the active form of vitamin D-was thought to function primarily as a regulator of calcium and phosphate metabolism. More diverse functionality was indicated by the discovery of the vitamin D receptor in tissues that are not involved in calcium and phosphate homeostasis. Detection of the vitamin D receptor in monocytes and activated T cells has sparked interest in the immunomodulatory properties of vitamin D. Here, we review the role of vitamin D in regulation of the immune system, and evidence for its involvement in the pathogenesis of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia.A multi-disciplinary group developed the consensus statements, reviewed the relevant literature, and voted on them anonymously using the Delphi method. The finalized statements were reviewed to determine the level of consensus, evidence quality and strength of recommendation.Infectious colitis must be excluded prior to diagnosing UC. Typical histology and macroscopic extent of the disease seen in the West is found in the Asia-Pacific region. Ulcerative colitis is increasing in many parts of Asia with gender distribution and age of diagnosis similar to the West. Extra-intestinal manifestations including primary sclerosing cholangitis are rarer than in the West. Clinical stratification of disease severity guides management. In Japan, leukocytapheresis is a treatment option. Access to biologic agents remains limited due to high cost and concern over opportunistic infections. The high endemic rates of hepatitis B virus infection require stringent screening before initiating immune-suppressive agents. Vaccination and prophylactic therapies should be initiated on a case-by-case basis and in accordance with local practice. Colorectal cancer complicates chronic colitis.A recent increase in UC is reported in the Asia-Pacific region. These consensus statements aim to improve the recognition of UC and assist clinicians in its management with particular relevance to the region.

Inflammatory bowel disease (IBD) was previously thought to be rare in Asia, but emerging data indicate rising incidence and prevalence of IBD in the region. The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology with the goal of developing best management practices, coordinating research, and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis, and management of Crohn's disease. The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses, and treatment availability. It does not intend to be all comprehensive and future revisions are likely to be required in this ever-changing field.