Wee Chian Lim

Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine.

Background : 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.

Mechanisms of disease: vitamin D and inflammatory bowel disease.

Until recently, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)—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.

The Asia-Pacific consensus on ulcerative colitis

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.

Asia Pacific Consensus Statements on Crohn's Disease Part 1: definition, diagnosis and epidemiology (Asia Pacific Crohn’s Disease Consensus Part 1)

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 Crohns 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.

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer

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.

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound.

Endoscopic ultrasound (EUS) and EUS‐guided fine‐needle aspiration (EUS‐FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS‐FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main‐duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side‐branch IPMN, and side‐branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS‐guided cyst ablation of mucinous pancreatic cysts is an alternative. As long‐term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Asia-Pacific consensus statements on Crohn's disease. Part 2: Management.

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 (APAGE) 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 (UC) 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 Crohns disease (CD). 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.

Risk of Major Abdominal Surgery in an Asian Population-based Crohnʼs Disease Cohort

Background:Crohns disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. Methods:This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan–Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. Results:The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9–13.0 yr) and median age at diagnosis 30.5 years (range, 19.5–43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17–40 yr, OR: 2.75, 95% confidence interval [CI], 1.14–7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14–5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20–11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0–58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19–0.78). Conclusions:Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

Mo1993 Identification of Individuals at High Risk of Gastric Cancer for Targeted Endoscopic Screening

Identification of Individuals at High Risk of Gastric Cancer for Targeted Endoscopic Screening Zhu Feng, Li Lin Lim, Calvin J. Koh, David E. Ong, Lee Guan Lim, Khek-Yu Ho, Chia Chung-King, Christopher J. Khor, Choon Jin Ooi, Kwong Ming Fock, Jimmy B. So, Wee Chian Lim, Khoon-Lin Ling, Tiing Leong Ang, Andrew S. Wong, Jaideepraj Rao, Andrea Rajnakova, Ming Teh, Manuel Salto-Tellez, Supriya Srivastava, Yik Ying Teo, Khay Guan Yeoh

Mo1571 Risk Stratification for Gastric Cancer Using Serum Pepsinogen and Helicobacter pylori Serology in a Chinese Population

Background: Several studies have evaluated various histologic predictors of invasion in breast and colon cancer biopsies. However, possible predictive factors of submucosal invasion in early gastric carcinomas have not been investigated. Identifying pathologic factors to predict submucosa invasion from pretreatment gastric biopsies would help select patients who may benefit from endoscopic mucosal resection (EMR). Methods: Pretreatment gastric biopsies from 60 patients with early gastric carcinomas with submucosal invasion who underwent EMR between 2002 and 2007 were reviewed. As a control, biopsies from 58 patients with intramucosal gastric carcinomas taken during the same period were evaluated. For validation of the results, another 702 gastric biopsies treated and confirmed as pT1 gastric carcinomas were also reviewed. For statistical analyses, Chi-square test, Fishers exact test using permutation method for multiple testing, and multiple logistic progression tests were used. Results: The depth of submucosa invasion varied from 50 μm to 3000 μm (mean 949 μm). In the biopsy specimens of carcinoma with submucosa invasion, differentiated histology, histologic heterogeneity, islands of muscularis mucosa, cribriform pattern, papillary feature, desmoplastic reaction, and intraglndular eosinophilic necrotic debris (IEND) were observed in 96.7%, 36.7%, 16.7%, 16.7%, 23.3%, 40%, and 46.7% of cases, respectively, compared to 100%, 5.2%, 0%, 1.7%, 5.2%, 19%, and 22.4% of intramucosal carcinoma biopsies. In multivariable analyses, histologic heterogeneity [odds ratio (OR), 9.59, p=0.002], IEND [OR, 6.23, p= 0.012], cribriform pattern [OR, 4.66, p=0.03], and papillary feature [OR, 5.52, p=0.018] were significantly associated with submucosal invasion in EMR specimens. In the validation cohort, histologic heterogeneity remained significant (p=0.003) with 48.7% sensitivity and 72.2% specificity, with positive predictive value of 43.5% [95% confidence interval (36.9%, 50.1%)] and negative predictive value of 75.3% [95% confidence interval (71.1%, 79.5%)]. Conclusion: In pretreatment gastric biopsies, histologic heterogeneity is a significant pathologic predictor of submucosal invasion. Additional prospective studies are warranted to find more sensitive and specific markers.