- Email: [email protected]
Su1972 Impact of Body Mass Index on Oncological Outcomes in Colorectal Cancer Patients Undergoing Surgery With Curative Intent
Su1969
AGA Abstracts
N-3 Fatty Acid Supplementation Improves Hepatic- and CardiometabolicRelated Biomarkers in Pediatric Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Intervention Schohraya Spahis, Fernando Alvarez, Edgard Delvin, Josee Dubois, Noel Peretti, Najma Ahmad, Alain Moreau, Carole Garofalo, An Tang, Ernest G. Seidman, Emile Levy Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver diseases in children around the world. It is closely associated with diverse conditions such as obesity, metabolic syndrome and cardiovascular diseases. NAFLD can progress to fibrosis, cirrhosis and hepatocellular carcinoma if it is not well treated. As growing evidence incriminates diet and nutrition in NAFLD pathogenesis, therapeutic strategies are urgently needed. Objectives: (1) To define alterations in fatty acid (FA) composition, lipid profile and fatty liver-related cardiometabolic markers of young French-Canadian subjects with NAFLD and (2) To test the effects of n-3 FA supplementation on FA composition and cardio-metabolic outcomes in NAFLD subjects. Methods: The clinical trial, registered as NCT02201160 on www.clinicaltrials.gov was performed on 20 boys (9 with moderate NAFLD and 11 with severe NAFLD according to transaminase levels and ultrasonographic steatosis score), aged between 8 and 18 years with a body mass index> 85th percentile were recruited. In the randomized, doubleblind trial, they received 1.2 g/day n-3 FA [eicosapentaenoic (EPA) and docosahexaenoic (DHA) or placebo (sunflower oil) for 6 months. Results: Baseline parameters of severe NAFLD subjects show metabolic disturbances characterized by insulin resistance (IR), elevated cholesterol/HDL-cholesterol ratio, oxidative stress, inflammation and ALT/AST ratio, along with decreased polyunsaturated FA, particularly EPA and DHA. Supplementation with n-3 PUFA resulted in (i) liver transaminase and dyslipidemia improvement (significant decreases in plasma triglycerides and apo B/A-I ratio); (ii) IR decline as reflected by HOMAIR index; (iii) inflammation lessening denoted by TNF-alowering and adiponectin augmentation; and (iv) a reduction in carotid intima-media thickness. Conclusions: As expected, derangements were observed in FA composition and cardiometabolic parameters of young French-Canadian patients with NAFLD. Improvements in FA composition as well as in biomarkers of liver functions and cardiometabolic risk factors were recorded following n-3 FA supplementation even in the absence of weight loss and activity pattern. These data suggest that n-3 FA may result in significant reductions in metabolic dysregulation and hepatic injury in children with NAFLD. Acknowledgment: This study was supported by the FRQS doctoral scholarship award, the J.A. DeSève Research Chair in Nutrition and NutriSanté Ponroy Inc (Gift for n-3 FA capsules).
Su1971 Chronic Hepatitis B Infection Is Not Associated With Increased Risk of Vascular Mortality While Having an Association With Metabolic Syndrome Aezam Katoonizadeh, maryam sharafkhah, Masoud Khoshnia, Hossein Poustchi, Reza Malekzadeh Background/aim: Results of different studies on the association between metabolic syndrome (MS) and chronic hepatitis B infection (CHB) are conflicting . This study aimed to assess the association of CHB with vascular mortality and MS using data from a large populationbased cohort study (Golestan Cohort Study) in Northern Iran, where the prevalence of CHB is the highest (7%) in the country. Patients and methods: A total of 12,781 participants including 2249 with CHB (HBsAg+/HBcAb+) and a random subsample of 10,532 HBsAg negative individuals were studied. Logistic regression model was used to assess the association between MS and CHB with adjustment for Age, ALT, PLT, alcohol intake, smoking, exercise, and socioeconomic status. Data were analyzed separately for males and females. MS was defined according to the ATPIII guidelines . Cox proportional hazards model was used to assess the hazard ratios of overall mortality and mortality from vascular events for patients with CHB after adjustment for confounding risk factors, compared with non-infected individuals. Results: Of the 1,178 men participants with CHB, 201 (17.2%) had metabolic syndrome, which was significantly lower than those without CHB (20.7%, P=0.007). This inverse association was remained significant after adjustments for confounding factors (OR (95%CI), 0.85 (0.79-0.99). Impaired FBS (OR (95%CI), 0.87 (0.75-1.00) and lower TG (OR (95%CI), 0.58 (0.49-0.68) levels were determinants of this inverse association. In contrast, infected women had higher prevalence of MS (41.4% vs 37.7% in none infected, P=0.02) which remained significant after adjustment for confounders (OR (95% CI); 1.23 (1.07-1.42), P< 0.004). This direct association was strongly related to impaired HDL (OR (95% CI); 1.35 (1.15-1.59), P= 0.001) and BP (OR (95% CI); 2.61(2.24-3.04), P< 0.001). The gender dependent association was related to BP and probably TG levels (P for interactions <0.001and 0.06 respectively). There was a significant association between CHB infection and overall mortality (hazard ratio (95% CI) of 1.44 (1.16-1.79), P < 0.001) after adjusting for other confounders. However, we found no association between CHB infection and mortality from vascular events (hazard ratio (95% CI) of 1.31 (0.93-1.84), P = 0.124) even after subgroup analysis by ALT. Furthermore, increased risk of overall mortality in CHB infected individuals was not related to MS and vice versa (P for interaction=0.06). Conclusions: Our results indicated a significant direct association between CHB infection and MS in women. However, CHB was inversely associated with MS in men. Further longitudinal studies should be done to investigate the exact impact of HBV infection on metabolic parameters and vascular pathology.
Su1968 Schlafen 3 Knockout Mice Display Gender-Differences in Weight Gain and Mucosal Biology Jun H. Lee, Pavlo L. Kovalenko, Lakshmi S. Chaturvedi, Marc D. Basson Enterocytic differentiation is critical to the response to prolonged fasting and likely to be important in adaptation to short gut syndrome. Exogenous adenoviral overexpression of Schlafen 3 (Slfn3) drives enterocytic differentiation in vitro in IEC-6 and Caco-2 cells as well as in vivo in live rat small bowel. However, no phenotype has previously been described for the Slfn3 knockout mouse. We conducted a pair feeding study in which Slfn3-heterozygous and Slfn3-knockout (KO) mice were pair-fed to wild-type mice (WT) of similar age, weight, and gender. Over 6 weeks of pair-feeding, female KO mice gained significantly less weight than their counterpart WT mice, while heterozygotes exhibited statistically significant intermediate weight gains (n=14-17 each, p<0.05). Although there was a similar stepwise pattern for mean weight gain among male KO, heterozygous and WT mice, the differences were markedly smaller and did not achieve statistical significance (n=19-26 each, p>0.05). Although the female KO mice ate slightly less food than the WT mice (n=14-17 each, p<0.05), the trends of weight loss between the genotypes were maintained when the weight gained or loss was standardized to oral intake (n=14-17 each, p<0.05). After completing the pair-feeding study, we used qRT-PCR to confirm the biochemical effects of the knockout, comparing WT and KO mice. As expected, Slfn3 was expressed in WT mice while Ct values approximated background in the KO mice. Since Slfn3 drives enterocytic sucrase-isomaltase (SI) expression, we then further examined SI expression in the mice. SI expression was markedly lower in the ileal mucosa of female KO mice than in female WT mice (n=5-7, p<0.05). In contrast, although SI expression tended to be somewhat lower in male KO mice than male WT mice, this difference was modest and did not achieve statistical significance. These results confirm that the loss of Slfn3 can have functional effects on weight gain during enteral nutrition. The gender difference in effect may reflect gender-based differences in compensation for the loss of Slfn3 that await further elucidation.
Su1972 Impact of Body Mass Index on Oncological Outcomes in Colorectal Cancer Patients Undergoing Surgery With Curative Intent Yuji Toiyama, Yasuhiro Inoue, Tadanobu Shimura, Hiroyuki Fujikawa, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Toshimitsu Araki, Koji Tanaka, Yasuhiko Mohri, Masato Kusunoki Objective: Excess body weight is an established risk factor for several types of cancer, including colorectal cancer (CRC). In particular, reliable epidemiological data reveal that obesity defined as body mass index (BMI) >30 increases cancer risk and cancer-specific mortality. Obesity is also considered to be a risk factor for postoperative morbidity after
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abdominal surgery. However, the effects of obesity on survival of CRC patients undergoing curative open or laparoscopic surgery are not fully understood. Aim: The aim of this study was to investigate the association between BMI and clinicopathological findings including preoperative laboratory data and survival outcome in CRC patients treated with curative intent, using two cohorts (open surgery and laparoscopic surgery groups). Methods:Clinicopathological findings including BMI and laboratory data (carcinoembryonic antigen and neutrophil/lymphocyte ratio [NLR]) from 358 curative CRC patients (open surgery group: n=157, laparoscopic surgery group: n=201) were assessed as indicators of survival outcome. BMI <20 was defined as underweight in both groups. Results: None of the categories of pathological findings were associated with BMI in both groups. Patients with BMI <20 showed significantly poorer overall survival (OS), and BMI<20 was an independent predictor of poor prognosis in CRC patients treated with open surgery (HR = 2.3214, P = 0.0425). In addition, patients with BMI <20 in the laparoscopic surgery group also had significantly worse OS and disease-free survival (DFS). Multivariate analysis demonstrated that BMI was validated as an independent predictor for OS (HR = 21.2890, P = 0.0003) and DFS (HR = 3.5590, P = 0.0254) in the laparoscopic surgery group. In addition, BMI <20 is an indicator of poor prognosis and early recurrence in CRC patients without lymph node metastases in both groups. BMI had a significant negative correlation with NLR, which reflected host immune response in both groups (open surgery group: r = −0.256, P = 0.0016, laparoscopic surgery group: r = −0.210, P = 0.0033). Conclusion: BMI of curative CRC patients is not affected completely by TNM stage, and is negatively correlated with NLR. Being underweight (BMI <20) preoperatively is an indicator for poor prognosis and early recurrence in CRC patients without cancer cachexia undergoing curative treatment. Although the underlying mechanisms were not fully investigated, unnoticed impairment of host immunity against micrometastatic tumors might be present in underweight patients.
Su1973 Morbid Obesity is Associated with Adverse Clinical Outcomes in Clostridium difficile infection: Results from the Nationwide Inpatient Sample Sushil Kumar Garg, Darrell Pardi, Sahil Khanna BACKGROUND & AIMS: Morbid obesity is associated with adverse clinical outcomes, but there are no studies assessing the impact of morbid obesity on Clostridium difficile infection (CDI)-related outcomes. We evaluated the impact of morbid obesity (BMI >40 kg/m2) on CDI- outcomes and health-care utilization. METHODS: The recent Nationwide Inpatient Sample from 2012 was reviewed to identify all adult inpatients ( ‡18 years) with a primary and secondary diagnosis of CDI (International classification of diseases - 9th edition [ICD9] code: 008.45) and patients with morbid obesity (ICD-9 codes: 278.01 & V85.40-44). Our primary outcomes were inpatient mortality, length of stay, and total charges; secondary outcomes included acute renal failure, acute respiratory failure and mechanical ventilation. Univariate and multivariable logistic regression (predicting nominal variable outcomes) and linear regression (predicting continuous variable outcomes) were performed. We compared the outcomes in patients with morbid obesity (BMI > 40) and normal weight (BMI < 25). Multiple variable regression analysis controlled for differences in sex, age, race, location of hospital, patient residence, insurance, hospital bed size, region, co morbidities, weekend admission, type of admission and teaching hospital status. RESULTS: Of 70,497 patients with CDI (median age 71 [range 18-90], 59% female), 3192 (4.5%) had morbid obesity. The overall mortality in CDI patients was 7.3%, median length of stay was 10.6 days (IQR 4-13), average charges were $84,604; rate of acute renal failure was 26.6%. CDI patients with morbid obesity had an increased odds of inpatient mortality (adjusted odds ratio, 1.23; CI 95% (1.1-1.4, p = 0.004), a longer LOS (13.4 vs 10.4 d; p < 0.001), and greater hospital charges ($114,165.2 vs $83,295.8; p < 0.001), compared with those with BMI < 25. Patients with CDI and morbid obesity had an increased odds of acute renal failure (adjusted odds ratio, 1.8; 95% CI (1.6-1.9)) compared to patients with CDI and BMI < 25. CONCLUSIONS: In patients with CDI, morbid obesity is associated with greater mortality, LOS, charges, acute renal failure and acute respiratory failure.
Su1975 Prevalence of Significant Hepatic Fibrosis and Cirrhosis Assessed by Various Non-Invasive Scores in Patients Attending the Diabetic Clinic Jun Liong Chin, Grace Chan, Abdur R. Aftab, Colm McGurk, Garry Courtney Background and Aims: Non-alcohol fatty liver disease (NAFLD) is common in diabetic patients with the metabolic syndrome. Patients with NAFLD can develop steatohepatitis and progress to cirrhosis. A number of non-invasive scores have been developed to identify patients at high risk of significant hepatic fibrosis and cirrhosis. The aim of this study is to apply a number of validated scores in patients attending the diabetic clinic to assess the prevalence of significant fibrosis and cirrhosis. Methods: We examined the data for all patients attending the diabetic clinic from March to June 2014 and only included patients with type 2 diabetes. Data were obtained from laboratory database and electronic diabetic patient record (Cellma). We applied the NAFLD fibrosis score (NFS), Fib-4 score, AST to Platelet Ratio Index (APRI), AST/ALT ratio and BARD score, to assess the prevalence of significant hepatic fibrosis and cirrhosis, in patients with diabetes. Results: 153 patients attending the diabetic clinic were included. The median age was 63 (IQR 56.0-71.5) years and 64.1% (98) of patients were male. More than half of our patients (56.2%; n=86) had a body mass index (BMI) >30kg/m2. Of these, 27.5% had a BMI of 30-35kg/m2, 14.4% of patients had a BMI of 35-40kg/m2 and another 14.4% had a BMI >40kg/m2. Using the NFS, almost a quarter of diabetic patients (24.2%, n=37) had significant fibrosis [median NFS score of 1.169(0.898-1.563)] while only one patient had significant fibrosis with the Fib-4 score of 3.28. Using the APRI, only 1.3% of patients were found to have cirrhosis [median APRI of 1.18(1.10-1.25)] while 4.6% of patients had significant hepatic fibrosis [0.78(0.720.83)]. Conversely, using the AST/ALT ratio and BARD score, the prevalence of significant hepatic fibrosis was 60.1%(92) and 90.2%(138) respectively, for diabetic patients. Only 1(0.7%) patient was found to have significant fibrosis when assessed with all 5 scores while 3(2%) patients did not have significant fibrosis with all of these scores. Conclusion: Identifying diabetic patients with significant hepatic fibrosis and cirrhosis remains challenging in clinical practice despite the description of various non-invasive scores. The prevalence of significant hepatic fibrosis and cirrhosis differ considerably between these scores, with limited correlation between them. The prevalence of significant hepatic fibrosis and cirrhosis based on a number of noninvasive scores
Su1974 CD24 Polymorphisms Are Associated With Obesity Risk Ilana Boustanai, Daniel Sion, Nataly Shemesh, Shiran Shapira, Dina Kazanov, Sally Zigdon, Lior Galazan, Ari Leshno, Abu-Abid Subhi, Sarah Kraus, Nadir Arber Background: Obesity is a global epidemic and a major risk factor for various health catastrophes. It is a multifactorial disease and has genetic and environmental etiology. Several studies have suggested candidate genes that may predispose to obesity. CD24 is a small, mucinlike glycoprotein that is expressed in many human malignancies (Sagiv, et al., 2006). We have recently found that CD24 knockout male (but not female) mice are obese with hyper insulin sensitivity than their wild-type (WT) littermates. Four single nucleotide polymorphisms (SNPs) in the CD24 gene are known to affect cancer risk and autoimmune diseases. C170T CD24 SNP results in the replacement of alanine by valine. This amino acid change is associated with increased risk for multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer risk (Huang, et al., 2015). Aim: To evaluate whether SNPs in the CD24 gene are associated with increased obesity risk. Methods: Genomic DNA was extracted from peripheral blood leukocytes of 158 obese Israeli patients (BMI ‡30; 122 males and 36 females), as well as age and gender-matched healthy controls (BMI £27; 178 males, 23 females). Samples were genotyped for the CD24 SNPs: C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818) by real-time PCR using Custom TaqMan® SNP allelic discrimination assays. c2 test was used to examine whether the CD24 gene polymorphism is associated with obesity. An association was considered statistically significant if p< 0.05. Results: C170T SNP is more prevalent in obese male than in normal weight males (p=0.087), (Fig.1), even after age adjustment (p=0.028; correlation coefficient= 1.367). This trend was not observed in obese females. This correlation becomes more significant for the obese males (> 50 year) (p=0.03; correlation coefficient=3.558), (Fig, 2). No correlation was found between the other three SNPs, in the 3'UTR, and the risk for obesity. Conclusions: The genetic variation C170T CD24 may be an important determinant for obesity in men, in particular above 50 year old. There is a need for a prospective life style intervention, in this group of patients, which may prevent obesity later in life.
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N-3 Fatty Acid Supplementation Improves Hepatic- and CardiometabolicRelated Biomarkers in Pediatric Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Intervention Schohraya Spahis, Fernando Alvarez, Edgard Delvin, Josee Dubois, Noel Peretti, Najma Ahmad, Alain Moreau, Carole Garofalo, An Tang, Ernest G. Seidman, Emile Levy Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver diseases in children around the world. It is closely associated with diverse conditions such as obesity, metabolic syndrome and cardiovascular diseases. NAFLD can progress to fibrosis, cirrhosis and hepatocellular carcinoma if it is not well treated. As growing evidence incriminates diet and nutrition in NAFLD pathogenesis, therapeutic strategies are urgently needed. Objectives: (1) To define alterations in fatty acid (FA) composition, lipid profile and fatty liver-related cardiometabolic markers of young French-Canadian subjects with NAFLD and (2) To test the effects of n-3 FA supplementation on FA composition and cardio-metabolic outcomes in NAFLD subjects. Methods: The clinical trial, registered as NCT02201160 on www.clinicaltrials.gov was performed on 20 boys (9 with moderate NAFLD and 11 with severe NAFLD according to transaminase levels and ultrasonographic steatosis score), aged between 8 and 18 years with a body mass index> 85th percentile were recruited. In the randomized, doubleblind trial, they received 1.2 g/day n-3 FA [eicosapentaenoic (EPA) and docosahexaenoic (DHA) or placebo (sunflower oil) for 6 months. Results: Baseline parameters of severe NAFLD subjects show metabolic disturbances characterized by insulin resistance (IR), elevated cholesterol/HDL-cholesterol ratio, oxidative stress, inflammation and ALT/AST ratio, along with decreased polyunsaturated FA, particularly EPA and DHA. Supplementation with n-3 PUFA resulted in (i) liver transaminase and dyslipidemia improvement (significant decreases in plasma triglycerides and apo B/A-I ratio); (ii) IR decline as reflected by HOMAIR index; (iii) inflammation lessening denoted by TNF-alowering and adiponectin augmentation; and (iv) a reduction in carotid intima-media thickness. Conclusions: As expected, derangements were observed in FA composition and cardiometabolic parameters of young French-Canadian patients with NAFLD. Improvements in FA composition as well as in biomarkers of liver functions and cardiometabolic risk factors were recorded following n-3 FA supplementation even in the absence of weight loss and activity pattern. These data suggest that n-3 FA may result in significant reductions in metabolic dysregulation and hepatic injury in children with NAFLD. Acknowledgment: This study was supported by the FRQS doctoral scholarship award, the J.A. DeSève Research Chair in Nutrition and NutriSanté Ponroy Inc (Gift for n-3 FA capsules).
Su1971 Chronic Hepatitis B Infection Is Not Associated With Increased Risk of Vascular Mortality While Having an Association With Metabolic Syndrome Aezam Katoonizadeh, maryam sharafkhah, Masoud Khoshnia, Hossein Poustchi, Reza Malekzadeh Background/aim: Results of different studies on the association between metabolic syndrome (MS) and chronic hepatitis B infection (CHB) are conflicting . This study aimed to assess the association of CHB with vascular mortality and MS using data from a large populationbased cohort study (Golestan Cohort Study) in Northern Iran, where the prevalence of CHB is the highest (7%) in the country. Patients and methods: A total of 12,781 participants including 2249 with CHB (HBsAg+/HBcAb+) and a random subsample of 10,532 HBsAg negative individuals were studied. Logistic regression model was used to assess the association between MS and CHB with adjustment for Age, ALT, PLT, alcohol intake, smoking, exercise, and socioeconomic status. Data were analyzed separately for males and females. MS was defined according to the ATPIII guidelines . Cox proportional hazards model was used to assess the hazard ratios of overall mortality and mortality from vascular events for patients with CHB after adjustment for confounding risk factors, compared with non-infected individuals. Results: Of the 1,178 men participants with CHB, 201 (17.2%) had metabolic syndrome, which was significantly lower than those without CHB (20.7%, P=0.007). This inverse association was remained significant after adjustments for confounding factors (OR (95%CI), 0.85 (0.79-0.99). Impaired FBS (OR (95%CI), 0.87 (0.75-1.00) and lower TG (OR (95%CI), 0.58 (0.49-0.68) levels were determinants of this inverse association. In contrast, infected women had higher prevalence of MS (41.4% vs 37.7% in none infected, P=0.02) which remained significant after adjustment for confounders (OR (95% CI); 1.23 (1.07-1.42), P< 0.004). This direct association was strongly related to impaired HDL (OR (95% CI); 1.35 (1.15-1.59), P= 0.001) and BP (OR (95% CI); 2.61(2.24-3.04), P< 0.001). The gender dependent association was related to BP and probably TG levels (P for interactions <0.001and 0.06 respectively). There was a significant association between CHB infection and overall mortality (hazard ratio (95% CI) of 1.44 (1.16-1.79), P < 0.001) after adjusting for other confounders. However, we found no association between CHB infection and mortality from vascular events (hazard ratio (95% CI) of 1.31 (0.93-1.84), P = 0.124) even after subgroup analysis by ALT. Furthermore, increased risk of overall mortality in CHB infected individuals was not related to MS and vice versa (P for interaction=0.06). Conclusions: Our results indicated a significant direct association between CHB infection and MS in women. However, CHB was inversely associated with MS in men. Further longitudinal studies should be done to investigate the exact impact of HBV infection on metabolic parameters and vascular pathology.
Su1968 Schlafen 3 Knockout Mice Display Gender-Differences in Weight Gain and Mucosal Biology Jun H. Lee, Pavlo L. Kovalenko, Lakshmi S. Chaturvedi, Marc D. Basson Enterocytic differentiation is critical to the response to prolonged fasting and likely to be important in adaptation to short gut syndrome. Exogenous adenoviral overexpression of Schlafen 3 (Slfn3) drives enterocytic differentiation in vitro in IEC-6 and Caco-2 cells as well as in vivo in live rat small bowel. However, no phenotype has previously been described for the Slfn3 knockout mouse. We conducted a pair feeding study in which Slfn3-heterozygous and Slfn3-knockout (KO) mice were pair-fed to wild-type mice (WT) of similar age, weight, and gender. Over 6 weeks of pair-feeding, female KO mice gained significantly less weight than their counterpart WT mice, while heterozygotes exhibited statistically significant intermediate weight gains (n=14-17 each, p<0.05). Although there was a similar stepwise pattern for mean weight gain among male KO, heterozygous and WT mice, the differences were markedly smaller and did not achieve statistical significance (n=19-26 each, p>0.05). Although the female KO mice ate slightly less food than the WT mice (n=14-17 each, p<0.05), the trends of weight loss between the genotypes were maintained when the weight gained or loss was standardized to oral intake (n=14-17 each, p<0.05). After completing the pair-feeding study, we used qRT-PCR to confirm the biochemical effects of the knockout, comparing WT and KO mice. As expected, Slfn3 was expressed in WT mice while Ct values approximated background in the KO mice. Since Slfn3 drives enterocytic sucrase-isomaltase (SI) expression, we then further examined SI expression in the mice. SI expression was markedly lower in the ileal mucosa of female KO mice than in female WT mice (n=5-7, p<0.05). In contrast, although SI expression tended to be somewhat lower in male KO mice than male WT mice, this difference was modest and did not achieve statistical significance. These results confirm that the loss of Slfn3 can have functional effects on weight gain during enteral nutrition. The gender difference in effect may reflect gender-based differences in compensation for the loss of Slfn3 that await further elucidation.
Su1972 Impact of Body Mass Index on Oncological Outcomes in Colorectal Cancer Patients Undergoing Surgery With Curative Intent Yuji Toiyama, Yasuhiro Inoue, Tadanobu Shimura, Hiroyuki Fujikawa, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Toshimitsu Araki, Koji Tanaka, Yasuhiko Mohri, Masato Kusunoki Objective: Excess body weight is an established risk factor for several types of cancer, including colorectal cancer (CRC). In particular, reliable epidemiological data reveal that obesity defined as body mass index (BMI) >30 increases cancer risk and cancer-specific mortality. Obesity is also considered to be a risk factor for postoperative morbidity after
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abdominal surgery. However, the effects of obesity on survival of CRC patients undergoing curative open or laparoscopic surgery are not fully understood. Aim: The aim of this study was to investigate the association between BMI and clinicopathological findings including preoperative laboratory data and survival outcome in CRC patients treated with curative intent, using two cohorts (open surgery and laparoscopic surgery groups). Methods:Clinicopathological findings including BMI and laboratory data (carcinoembryonic antigen and neutrophil/lymphocyte ratio [NLR]) from 358 curative CRC patients (open surgery group: n=157, laparoscopic surgery group: n=201) were assessed as indicators of survival outcome. BMI <20 was defined as underweight in both groups. Results: None of the categories of pathological findings were associated with BMI in both groups. Patients with BMI <20 showed significantly poorer overall survival (OS), and BMI<20 was an independent predictor of poor prognosis in CRC patients treated with open surgery (HR = 2.3214, P = 0.0425). In addition, patients with BMI <20 in the laparoscopic surgery group also had significantly worse OS and disease-free survival (DFS). Multivariate analysis demonstrated that BMI was validated as an independent predictor for OS (HR = 21.2890, P = 0.0003) and DFS (HR = 3.5590, P = 0.0254) in the laparoscopic surgery group. In addition, BMI <20 is an indicator of poor prognosis and early recurrence in CRC patients without lymph node metastases in both groups. BMI had a significant negative correlation with NLR, which reflected host immune response in both groups (open surgery group: r = −0.256, P = 0.0016, laparoscopic surgery group: r = −0.210, P = 0.0033). Conclusion: BMI of curative CRC patients is not affected completely by TNM stage, and is negatively correlated with NLR. Being underweight (BMI <20) preoperatively is an indicator for poor prognosis and early recurrence in CRC patients without cancer cachexia undergoing curative treatment. Although the underlying mechanisms were not fully investigated, unnoticed impairment of host immunity against micrometastatic tumors might be present in underweight patients.
Su1973 Morbid Obesity is Associated with Adverse Clinical Outcomes in Clostridium difficile infection: Results from the Nationwide Inpatient Sample Sushil Kumar Garg, Darrell Pardi, Sahil Khanna BACKGROUND & AIMS: Morbid obesity is associated with adverse clinical outcomes, but there are no studies assessing the impact of morbid obesity on Clostridium difficile infection (CDI)-related outcomes. We evaluated the impact of morbid obesity (BMI >40 kg/m2) on CDI- outcomes and health-care utilization. METHODS: The recent Nationwide Inpatient Sample from 2012 was reviewed to identify all adult inpatients ( ‡18 years) with a primary and secondary diagnosis of CDI (International classification of diseases - 9th edition [ICD9] code: 008.45) and patients with morbid obesity (ICD-9 codes: 278.01 & V85.40-44). Our primary outcomes were inpatient mortality, length of stay, and total charges; secondary outcomes included acute renal failure, acute respiratory failure and mechanical ventilation. Univariate and multivariable logistic regression (predicting nominal variable outcomes) and linear regression (predicting continuous variable outcomes) were performed. We compared the outcomes in patients with morbid obesity (BMI > 40) and normal weight (BMI < 25). Multiple variable regression analysis controlled for differences in sex, age, race, location of hospital, patient residence, insurance, hospital bed size, region, co morbidities, weekend admission, type of admission and teaching hospital status. RESULTS: Of 70,497 patients with CDI (median age 71 [range 18-90], 59% female), 3192 (4.5%) had morbid obesity. The overall mortality in CDI patients was 7.3%, median length of stay was 10.6 days (IQR 4-13), average charges were $84,604; rate of acute renal failure was 26.6%. CDI patients with morbid obesity had an increased odds of inpatient mortality (adjusted odds ratio, 1.23; CI 95% (1.1-1.4, p = 0.004), a longer LOS (13.4 vs 10.4 d; p < 0.001), and greater hospital charges ($114,165.2 vs $83,295.8; p < 0.001), compared with those with BMI < 25. Patients with CDI and morbid obesity had an increased odds of acute renal failure (adjusted odds ratio, 1.8; 95% CI (1.6-1.9)) compared to patients with CDI and BMI < 25. CONCLUSIONS: In patients with CDI, morbid obesity is associated with greater mortality, LOS, charges, acute renal failure and acute respiratory failure.
Su1975 Prevalence of Significant Hepatic Fibrosis and Cirrhosis Assessed by Various Non-Invasive Scores in Patients Attending the Diabetic Clinic Jun Liong Chin, Grace Chan, Abdur R. Aftab, Colm McGurk, Garry Courtney Background and Aims: Non-alcohol fatty liver disease (NAFLD) is common in diabetic patients with the metabolic syndrome. Patients with NAFLD can develop steatohepatitis and progress to cirrhosis. A number of non-invasive scores have been developed to identify patients at high risk of significant hepatic fibrosis and cirrhosis. The aim of this study is to apply a number of validated scores in patients attending the diabetic clinic to assess the prevalence of significant fibrosis and cirrhosis. Methods: We examined the data for all patients attending the diabetic clinic from March to June 2014 and only included patients with type 2 diabetes. Data were obtained from laboratory database and electronic diabetic patient record (Cellma). We applied the NAFLD fibrosis score (NFS), Fib-4 score, AST to Platelet Ratio Index (APRI), AST/ALT ratio and BARD score, to assess the prevalence of significant hepatic fibrosis and cirrhosis, in patients with diabetes. Results: 153 patients attending the diabetic clinic were included. The median age was 63 (IQR 56.0-71.5) years and 64.1% (98) of patients were male. More than half of our patients (56.2%; n=86) had a body mass index (BMI) >30kg/m2. Of these, 27.5% had a BMI of 30-35kg/m2, 14.4% of patients had a BMI of 35-40kg/m2 and another 14.4% had a BMI >40kg/m2. Using the NFS, almost a quarter of diabetic patients (24.2%, n=37) had significant fibrosis [median NFS score of 1.169(0.898-1.563)] while only one patient had significant fibrosis with the Fib-4 score of 3.28. Using the APRI, only 1.3% of patients were found to have cirrhosis [median APRI of 1.18(1.10-1.25)] while 4.6% of patients had significant hepatic fibrosis [0.78(0.720.83)]. Conversely, using the AST/ALT ratio and BARD score, the prevalence of significant hepatic fibrosis was 60.1%(92) and 90.2%(138) respectively, for diabetic patients. Only 1(0.7%) patient was found to have significant fibrosis when assessed with all 5 scores while 3(2%) patients did not have significant fibrosis with all of these scores. Conclusion: Identifying diabetic patients with significant hepatic fibrosis and cirrhosis remains challenging in clinical practice despite the description of various non-invasive scores. The prevalence of significant hepatic fibrosis and cirrhosis differ considerably between these scores, with limited correlation between them. The prevalence of significant hepatic fibrosis and cirrhosis based on a number of noninvasive scores
Su1974 CD24 Polymorphisms Are Associated With Obesity Risk Ilana Boustanai, Daniel Sion, Nataly Shemesh, Shiran Shapira, Dina Kazanov, Sally Zigdon, Lior Galazan, Ari Leshno, Abu-Abid Subhi, Sarah Kraus, Nadir Arber Background: Obesity is a global epidemic and a major risk factor for various health catastrophes. It is a multifactorial disease and has genetic and environmental etiology. Several studies have suggested candidate genes that may predispose to obesity. CD24 is a small, mucinlike glycoprotein that is expressed in many human malignancies (Sagiv, et al., 2006). We have recently found that CD24 knockout male (but not female) mice are obese with hyper insulin sensitivity than their wild-type (WT) littermates. Four single nucleotide polymorphisms (SNPs) in the CD24 gene are known to affect cancer risk and autoimmune diseases. C170T CD24 SNP results in the replacement of alanine by valine. This amino acid change is associated with increased risk for multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer risk (Huang, et al., 2015). Aim: To evaluate whether SNPs in the CD24 gene are associated with increased obesity risk. Methods: Genomic DNA was extracted from peripheral blood leukocytes of 158 obese Israeli patients (BMI ‡30; 122 males and 36 females), as well as age and gender-matched healthy controls (BMI £27; 178 males, 23 females). Samples were genotyped for the CD24 SNPs: C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818) by real-time PCR using Custom TaqMan® SNP allelic discrimination assays. c2 test was used to examine whether the CD24 gene polymorphism is associated with obesity. An association was considered statistically significant if p< 0.05. Results: C170T SNP is more prevalent in obese male than in normal weight males (p=0.087), (Fig.1), even after age adjustment (p=0.028; correlation coefficient= 1.367). This trend was not observed in obese females. This correlation becomes more significant for the obese males (> 50 year) (p=0.03; correlation coefficient=3.558), (Fig, 2). No correlation was found between the other three SNPs, in the 3'UTR, and the risk for obesity. Conclusions: The genetic variation C170T CD24 may be an important determinant for obesity in men, in particular above 50 year old. There is a need for a prospective life style intervention, in this group of patients, which may prevent obesity later in life.
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AGA Abstracts