Khoon-Lin Ling

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

Objective The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. Design 442 incident cases (186 Crohns disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. Results In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. Conclusions This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

Macrophages in human colorectal cancer are pro-inflammatory and prime T cells towards an anti-tumour type-1 inflammatory response.

High macrophage infiltration into tumours often correlates with poor prognoses; in colorectal, stomach and skin cancers, however, the opposite is observed but the mechanisms behind this phenomenon remain unclear. Here, we sought to understand how tumour‐associated macrophages (TAMs) in colorectal cancer execute tumour‐suppressive roles. We found that TAMs in a colorectal cancer model were pro‐inflammatory and inhibited the proliferation of tumour cells. TAMs also produced chemokines that attract T cells, stimulated proliferation of allogeneic T cells and activated type‐1 T cells associated with anti‐tumour immune responses. Using colorectal tumour tissues, we verified that TAMs in vivo were indeed pro‐inflammatory. Furthermore, the number of tumour‐infiltrating T cells correlated with the number of TAMs, suggesting that TAMs could attract T cells; and indeed, type‐1 T cells were present in the tumour tissues. Patient clinical data suggested that TAMs exerted tumour‐suppressive effects with the help of T cells. Hence, the tumour‐suppressive mechanisms of TAMs in colorectal cancer involve the inhibition of tumour cell proliferation alongside the production of pro‐inflammatory cytokines, chemokines and promoting type‐1 T‐cell responses. These new findings would contribute to the development of future cancer immunotherapies based on enhancing the tumour‐suppressive properties of TAMs to boost anti‐tumour immune responses.

Clinical characteristics of ulcerative colitis in Singapore, a multiracial city-state.

Background Ulcerative colitis (UC) is rare in Asia. Singapore is an ethnically heterogeneous city–state with a population made up of Chinese (77%), Indians (7.5%), and Malays (14%). This study describes and compares the characteristics of Chinese, Malay, and Indian patients with UC. Study Retrospective chart review was performed of 235 patients seen in the largest tertiary care hospital in Singapore between 1971 and June 2000. Results There were 169 (72%) Chinese, 24 (10%) Malays, and 42 (18%) Indians with UC. Male-to-female ratio was 1.8:1 (150:85). Most patients in all three races presented between the ages of 20 and 39 years. No bimodal peak in the age at presentation was seen. The median period from onset of symptoms to diagnosis was 1 month in all three races. More Malay (57%) and Indian (55%) patients had colitis extending proximal to splenic flexure at presentation compared with Chinese (32%) patients (p = 0.04). There were more Indian patients (29%) with severe disease at onset compared with Chinese (12%) and Malay (22%) patients (p = 0.035). Thirty-one percent of patients had only one episode of colitis, 12% were steroid dependent, and 4% were steroid refractory. Proctocolectomy was needed in 31 (18.3%) Chinese, 3 (12.5%) Malay, and 4 (9.5%) Indian patients. Extraintestinal manifestations were found in 6% of the Chinese, 12% of Malay patients, and 14% of Indian patients. The most common extraintestinal manifestation was arthritis, present in 6.4% of patients. Conclusion There were more Indians with UC than expected in this population. Whereas Indian and Malay patients have more extensive and severe disease at presentation than Chinese patients, this does not predict for more refractory disease or a greater need for surgery.

Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients

Background: Azathioprine (AZA) is widely used to treat corticosteroid (CS)‐dependent IBD patients but evidence supporting its use in Asian IBD patients is limited. We evaluated the efficacy of AZA in a single‐center cohort of CS‐dependent Asian IBD patients. Methods: Patients treated with AZA were identified from our registry and the medical records were reviewed. Inclusion criterion was: first course of AZA and treatment duration ≥6 months. Clinical response was assessed at 6 months and classified as complete response, partial response, and nonresponse. Factors associated with response (age, gender, ulcerative colitis [UC] extent, Crohns disease [CD] behavior, ethnicity, concomitant 5‐aminosalicylates/sulfasalazine, baseline activity, disease duration, leukocyte count, mean corpuscular volume, and AZA dose) were analyzed using the chi‐square or Mann–Whitney U‐test. Probability of sustained remission was estimated using the Kaplan–Meier method. Differences in survival curves between factors were tested with log‐rank tests. Results: Sixty‐four patients were included. At baseline the median age was 37.5 (range, 15–76) years, 50% male, 59.4% Chinese, 50% CD, 50% UC, and mean CS dose 20.2 (SD 10.9) mg. At month 6, complete response was 48.4% (95% confidence interval [CI], 36.7–61.3), partial response 45.1% (95% CI, 32.8–58.3), and nonresponse 7.8% (95% CI, 2.6–17.3). Partial responders had mean CS dose reductions of 11.7 mg (95% CI, 7.2–16.4, P < 0.001). The proportion of patients with sustained remission was 0.87 (95% CI, 0.73–1.0) at 2 years, 0.76 (95% CI, 0.57–0.95) at 3 years, and 0.61 (95% CI, 0.30–0.91) at 5 years of AZA treatment. Female gender was positively associated with sustained remission. Conclusions: Our study demonstrates the short‐ and long‐term effectiveness of AZA therapy among CS‐dependent Asian IBD patients. (Inflamm Bowel Dis 2011)

78 Incidence and Phenotype of Inflammatory Bowel Disease From 13 Countries in Asia-Pacific: Results From the Asia-Pacific Crohn's and Colitis Epidemiologic Study 2011-2013

Incidence and Phenotype of Inflammatory Bowel Disease From 13 Countries in Asia-Pacific: Results From the Asia-Pacific Crohns and Colitis Epidemiologic Study 2011-2013 Siew C. Ng, Gilaad Kaplan, Rupa Banerjee, Shu-Chen Wei, Whitney Tang, Zhirong Zeng, Min-hu Chen, Hong Yang, H. Janaka de Silva, Madunil A Niriella, David E. Ong, KhoonLin Ling, Ida Hilmi, Pises Pisespongsa, Satimai Aniwan, Julajak Limsrivilai, Murdani Abdullah, Vui Heng Chong, Qian Cao, Yinglei Miao, Arlinking K. Ong-Go, Sally Bell, Olga Niewiadomski, Michael A. Kamm, Ka Kei Ng, Hon Ho Yu, Yu-Fang Wang, Qin Ouyang, Khean Lee Goh, Hung-Hsin Lin, Wei-Chen Lin, Kaichun Wu, Marcellus Simadibrata, Francis K. Chan, Joseph Sung

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.

Population Density and Risk of Inflammatory Bowel Disease: A Prospective Population-Based Study in 13 Countries or Regions in Asia-Pacific

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn’s disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43–1.57). India (9.31; 95% CI: 8.38–10.31) and China (3.64; 95% CI, 2.97–4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01–4.76]) and CD (IRR: 3.28; 95% CI: 1.83–9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10–5.16) and UC (IRR: 2.63; 95% CI: 1.2–5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91–0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05–1.24) was observed for CD incidence in China. This study received IRB approval. CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.

Tu1464 Retrospective Cohort Study of the Clinical Outcome of Parental Nutrition Lipid Formulations Containing Reduced Omega-6 Fatty Acids Compared to Soybean Lipid

BackgroundNutritional intake is often compromised in themonths following esophagogastric resection. Enteral nutrition has been used as an adjunct to oral intake but studies evaluating the role of extended jejunostomy feeding (JEJ) following hospital discharge are lacking. Methods As part of a randomized controlled trial investigating the effect of six weeks of home jejunostomy feeding, nutritional intake was assessed at 4 time points: hospital discharge, 6 weeks after discharge, 3 and 6 months post surgery. Dietary intake was assessed using 3 day dietary records, analysed using Dietplan6®. Information on JEJ intake was collected for the same period. Ideal nutritional requirements for energy were calculated using the Henry equation adjusted for activity level. Oral intake was considered adequate if reported intake provided >75% of estimated energy needs. Results 54 participants were enrolled in the study. There were 13 early withdrawals leaving 41 participants for analysis. Surgery comprised esophagectomy in 32 participants and total gastrectomy in 9. Twenty participants were randomised to a planned program of home JEJ feeding providing 50% of energy and protein requirements, inaddition to usual dietary intake. Twenty-one participants in the control group received care as usual with jejunostomy feeding being stopped on discharge from hospital. 17/20 participants (85%) in the intervention group received treatment as allocated. Seven participants (35%) in the control group had to recommence home feeding due to clinical and/or nutritional need. At the time of hospital discharge, dietary intake was poor in both groups with JEJ feeding still meeting the energy requirements of most participants. By 6 weeks post hospital discharge, oral nutritional intake remained inadequate in 47% and 50% of the intervention and control group respectively. Total calorie intake was adequate in the intervention group because of the contribution from jejunostomy feeding (Table). Conclusions This study has shown that energy requirements are frequently inadequate in patients after esophagectomy and total gastrectomy in the months after surgery. It has also demonstrated that supplementary jejunostomy feeding may make an important contribution to nutritional requirements in these early months.

Su1301 Incidence and Phenotype of Inflammatory Bowel Disease From 2012-2013 Across 9 Countries in Asia: Results From the 2012 Access Inception Cohort

AGA Poster session Abstract (Su1301) Digestive Disease Week (DDW), May 16-19, 2015, Washington DC