Day 2 :
Keynote Forum
Nathalie Rivard
University de Sherbrooke, Canada
Keynote: The complex role of SHP-2 tyrosine phosphatase in the development of colorectal cancer
Time : 10:00-10:45 A.M.
Biography:
Nathalie Rivard received her Ph.D. from Université de Sherbrooke in 1994 and completed a 3.5-year postdoctorate at the Centre de Biochimie-CNRS, Université de Nice, in France with Dr. J. Pouysségur in 1997. Then, she accepted a faculty position in the Department of Anatomy and Cell Biology at the Faculté de Médecine et des Sciences de la santé de l’Université de Sherbrooke. Rivard’s research focuses on the analysis of signalling pathways that control proliferation, differentiation, tumorigenesis and inflammatory response of intestinal epithelial cells. She has published more than 80 papers in reputed journals. She is the recipient of 2013 Canadian Association of Gastroenterology Research Excellence Award and holds a Canada Research Chair.
Abstract:
Colorectal cancer (CRC) is the third most common cancer in the world. A major risk factor to develop CRC is the presence of chronic inflammation in the colon. But how chronic inflammation contributes to the development of CRC is not so clear. In seeking to answer this question, we have focused on the signalling molecule SHP-2, a tyrosine phosphatase modulating cellular signals induced by both growth factors and pro-inflammatory cytokines. Polymorphisms in the PTPN11 locus encoding SHP-2 have been reported to be markers of colitis susceptibility. Conversely, gain-of-function mutations in PTPN11 have recently been associated with sporadic CRC. To investigate the role of SHP-2 in intestinal homeostasis, we have generated mice with an intestinal epithelial cell (IEC)-specific deletion of its expression. We demonstrated that IEC disruption of SHP-2 causes severe chronic inflammation in the colon. This inflammatory phenotype is associated with a dramatic increase in proliferation and activation of Wnt/b-catenin, NFkB and STAT3 signallings in colonic epithelium. With age, these mice develop malignant lesions in the colon suggesting that SHP-2 can act as a tumor suppressor in this tissue. Furthermore, SHP-2 epithelial deficiency severely increased colon tumor load in Apcmin/+ mice. Aside from these observations, we found increased expression and activating mutations of SHP-2 in sporadic human colorectal tumors and SHP-2 silencing markedly attenuated KRAS-induced transformation of IECs in culture. Hence, this suggests that SHP-2 can act as an oncogene in the colonic epithelium. Opposing roles for SHP-2 in promoting and suppressing tumorigenesis in the large intestine are therefore proposed.
- Gastrointestinal Immunology & Clinical Nutrition in Gastrointestinal Diseases
Location: Room 1
Session Introduction
Ghadah AlSuhaibani
King Saud University, Saudi Arabia
Title: Importance of autoantibody screening in diagnosis of celiac disease
Biography:
Ghadah is a 4th year medical student at King Saud University, Riyadh ,Saudi Arabia.
Abstract:
Background: Although small bowel biopsy is considered as the gold standard for diagnosis of celiac disease (CD) detection of autoantibodies is usually the initial step in diagnosis of CD.
Objective: This study was performed to assess the performance of each celiac specific auto antibody against the gold standard.
Methods: This retrospective study included 267 patients with clinical suspicion of CD who underwent investigations for diagnosis of CD between March 2011 and June 2014 at King Khalid University Hospital, Riyadh. The panel of celiac specific antibodies tested comprised of anti-gliadin IgG and IgA, anti-tissue Transglutaminase IgG (anti-tTGG) and IgA (anti-tTGA), anti-endomysium and anti-reticulin antibodies. Anti-endomysium and anti-reticulin antibodies were tested by immunofluorescence and the others were assessed by ELISA.
Results: Out of the total only 61 patients including 35 females and 26 males (mean age 26+11 years) were subjected to small bowel biopsy testing with 37 positive and 24 negative results. Among the six autoantibodies assessed anti-tTGA had a sensitivity of 97.3%, specificity of 83%, positive predictive value (PPV) of 90% and a negative predictive value (NPV) of 95%. Anti-endomysium antibody had a sensitivity of 62.1%, specificity of 95.7%, PPV of 95.8% and NPV of 62.2%. None of the other autoantibodies displayed any notable performance. Receiver operator curve analysis also confirmed the diagnostic accuracy of anti-tTGA with 90.3% area under curve (AUC) followed by anti-endomysium antibody with 70% AUC.
Conclusion: In the presence of relevant history anti-TGA as a single test can be used as an initial screening test for CD.
Rasha Dosh
Sheffield Hallam University, UK
Title: Interleukin-1 receptor antagonist knockout mice as a model of the inflammatory bowel disease
Biography:
Rasha has completed her MSc from Al-Mustansiriyah University and worked as a lecturer at University of Kufa college of Medicine/Iraq. She has published 4 papers in college of medicine journals. She is currently a second year PhD student at Sheffield Hallam University/ UK.
Abstract:
The inflammatory cytokine Interleukin 1 (IL-1) is an important mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). The activity of IL-1 is inhibited by a natural inhibitor: interleukin 1 receptor antagonist (IL-1Ra). The balance between IL-1 and IL-1Ra plays a vital role in diseases. We investigated whether inflammatory bowel disease could be induced spontaneously by the removal of IL-1Ra in mice. Histological staining was performed on BALB/C mice to characterize the morphology and enzyme activity of the small intestine from different ages and genotypes. Wild type mice served as a negative control. Twenty well oriented villi/crypt units and villus width at midvillus in longitudinal tissue sections were measured in the jejunum and ileum. The number of goblet cells per villi was determined. Immunohistochemical staining was performed to localise and detect MUC2, MUC5AC, MMP2, MMP9, ADAMTS1, IL-1β and TNFα. The results showed that there was a significant decrease in the villi/crypts units' height in the jejunum and ileum whereas the width of the villi was increased in the jejunum and decreased in the ileum. The number of goblet cells per villi was increased in knockout mice compared with wild type mice. Research is ongoing for the analysis of the immunohistochemistry. We conclude that IL-1Ra knockout mice could act as a model for inflammatory bowel disease highlighting the importance of IL-1 in this disorder.
Pochamana Phisalprapa
Mahidol University, Thailand
Title: Cost-effectiveness Analysis of Ultrasonography Screening for Non-Alcoholic Fatty Liver Disease in Metabolic Syndrome Patients
Biography:
Pochamana Phisalprapa, M.D. is a gastroenterologist and medical instructor at Faculty of Medicine Siriraj Hospital, Mahidol University. She has completed her M.Sc. in Health Economics and Health Care Management at Chulalongkorn University. She has published more 10 papers in reputed journals.
Abstract:
Background & Aims:Non-alcoholic fatty liver disease (NAFLD) can be early diagnosed by noninvasive ultrasonography. Currently, there is no cost-effectiveness analysis of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients. This study aimed to estimate costs and clinical outcomes of such program in Thailand. Methods:A cost-effectiveness analysis using decision tree and Markov models to estimate lifetime costs and health benefits of screening program versus no screening based on a cohort of 509 Thai metabolic syndrome patients from the largest university hospital in Thailand under societal perspective. Effectiveness and utility parameters were based on literatures, while costs and mortality parameters were determined using Thailand database. Costs were presented as year 2014 United States Dollar (USD) values. The results were reported as incremental cost-effectiveness ratios (ICERs) in USD per quality-adjusted life year (QALY) gained with discount rate of 3%. A series of sensitivity analyses including a Monte Carlo simulation were performed to assess the influence of parameter uncertainty on the results. Results:Ultrasonography screening of 50 years-old metabolic syndrome patients with intensive weight reduction program was cost-effective with ICERs of 958 USD/QALY gained when compared with no screening. According to willingness-to-pay of Thailand (4,848 USD/QALY gained), the probability of being cost-effective was 67%. Screening at ages before 45 years was cost-savings while screening at age between 45-64 years was cost-effective. Conclusion:For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Our findings can be used as part of evidence-informed decision making.
Engelbert Simon
Cardinal Santos Medical Center, Philippines
Title: Etiology, Clinical Profile, and Predictors of Mortality of Acute-On-Chronic Liver Failure in a Tertiary Hospital: A Retrospective Study
Biography:
Dr. Perillo graduated with a Bachelor of Science degree in Medical Technology from the Faculty of Pharmacy, University of Santo Tomas, finishing as Cum Laude. He obtained his medical degree from the Faculty of Medicine and Surgery, University of Santo Tomas in 2012, where he had been on the dean’s list for three years. He finished his post-graduate internship in Cardinal Santos Medical Center in 2013, being awarded as the Most Outstanding Intern. Currently, he is a third year internal medicine resident in the above-mentioned hospital.
Abstract:
Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity defined as a clinical syndrome in which two insults to the liver are operating simultaneously, one of them being ongoing and chronic, and the other, acute. The objective is to determine the causes and clinical profiles of ACLF at Cardinal Santos Medical Center in the Philippines, and in so doing, find instruments to help physicians predict mortality. This retrospective study was conducted at the Department of Internal Medicine of Cardinal Santos Medical Center. This study included all the patients who met the inclusion criteria of ACLF based on the Asian Pacific Association for the Study of the Liver (APASL) criteria from 2013-2015. Comparison between the survivors and non-survivors was done using the Mann-Whitney U test as a statistical tool. Associations of sex, encephalopathy, ascites and acute insults to mortality were determined by the Fisher-Exact test. Logistic regression was used to determine the important factors to predict mortality. The leading acute insult identified was alcohol accounting for 25.8%. Mortality is associated with the following: elevated bilirubin, elevated INR, low PT % Activity, elevated AST, elevated ALT, elevated creatinine, elevated MELD and elevated MELDNa. Significant association between encephalopathy and mortality was detected at 5% level of significance. The probability of death in patients with ACLF increased with the rise in bilirubin, INR, AST, ALT or creatinine levels. Encephalopathy is associated to “death due to ACLF”. Based on initial analysis, the following factors are the significant predictors of mortality: MELD, MELDNa and INR.
Inggar Armytasari
Gadjah Mada University, Indonesia
Title: ASSOCIATION BETWEEN CLINICAL SIGN AND COLORECTAL MUCOSAL LESION SEVERITY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Biography:
Inggar Armytasari completed her bachelor of medicine at the age of 21 from Gadjah Mada University. Currently she is undergoing a clinical rotation at Sardjito Hospital, Yogyakarta. Her interest is in Gastrointestinal Department, especially in Pediatric Gastroenterology.
Abstract:
Inflammatory bowel disease (IBD) is an idiopathic inflammatoric disease in gastrointestinal tract. The clinical signs of IBD include chronic diarrhea, with or without mucous and/or with or without rectal bleeding. It hasn’t surely been known that there is a positive correlation between clinical sign and colorectal mucosal lesion severity in the IBD patients.
This study aims to determine the relationship between clinical sign in inflammatory bowel disease patients with the varying colorectal mucosal lesion. The study was conducted in a retrospective cross sectional using the medical records data from both inpatient dan outpatient with IBD in Sardjito General Hospital from January 2012 until July 2014.
From 65 data (42 men, 23 women, age 18 to 97 years old (49,94±18,25)), there is an insignificant weak positive correlation between clinical signs and lesion severity in IBD (p=0,0916, r=0,211), also in proctitis (p=0,1543, r=0,2876). Meanwhile in left-sided colitis, the correlation is insignificant and has a very weak positive correlation (p=0,9518, r=0,0125).
The only significant and stronger correlation is the correlation between rectal bleeding and lesion severity in the proctitis patients with p=0,0053 and r=0,5310.
So it can be concluded that there is an insignificant weak positive correlation between clinical signs and lesion severity in IBD, except for the proctitis where the correlation between rectal bleeding and lesion severuty is rather high. From this conclusion we can assume that clinical signs only cannot reflect the diseasse severuty of IBD, with the exception of proctitis where the eseverity of rectal bleeding can also depict the severity of the lesion.