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Sa1476 Lifetime Alcohol Intake and Pattern of Alcohol Consumption in Patients With Alcohol Induced Pancreatitis
AGA Abstracts
of these patients and 2 developed collections in areas not specifically drained by the indwelling trans-enteric stents. No patients required surgery or developed PCF. CONCLUSIONS The stated therapeutic goals of combined endoscopic and percutaneous drainage of WOPN- single-digit mortality, absence of PCF and avoidance of surgery- are durable in a large cohort of patients over a long period of follow-up. Recurrent pancreatic fluid collections are seen and, when symptomatic, are amenable to endoscopic or percutaneous drainage.
All estimates are adjusted for sex, age, calendar year, education, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases Sa1478 Serum Galectin -1 and Galectin-3 are Increased in Diet-Induced Obesity and Associated With Infiltrate and Necrosis in Experimental Acute Pancreatitis in Mice Maria Pini, Elise Malecki, Davina H. Rhodes, Karla J. Castellanos, Robert J. Cabay, Douglas R. Thompson, Giamila Fantuzzi
Sa1476 Lifetime Alcohol Intake and Pattern of Alcohol Consumption in Patients With Alcohol Induced Pancreatitis Einar Bjornsson, Jon K. Nielsen
The severity of acute pancreatitis is increased in obese individuals, and the mechanisms by which obesity predisposes toward inflammation are under study. Galectin-1 (Gal-1) and galectin-3 (Gal-3) are involved in epithelial-stromal-immune cell interactions in inflammation. We hypothesized that Gal-1 and Gal-3 would be increased in obesity and with the severity of experimental acute pancreatitis. Male C57BL6 mice were fed either chow or highfat diet (60% kcal/fat) for 13 weeks beginning at 4 weeks of age to produce lean and dietinduced obese mice (DIO), respectively. At 17 weeks of age, lean and DIO mice received i.p. injections of IL-12 (125 ng/mouse) and IL-18 (750 ng/mouse), and were killed either without injections (time =0 days) or at 1, 3, 7, and 15 days post-injection. Effects of DIO and time on serum Gal-1 and Gal-3 levels were analyzed with two-way ANOVA. There were significant main effects of DIO for serum Gal-1 and Gal-3 (both p<0.001), with both measures consistently higher across time for DIO mice. There were also significant time main effects for both serum Gal-1 and Gal-3 (both p<0.01). For serum Gal-3 there was a DIO x time interaction (p<0.001), in that the lean mice experienced a quicker return to normal concentrations relative to the obese mice. In an additional analysis, Pearson correlation coefficients were obtained for serum galectins vs. histologic scores. Gal-1 correlated with the degree of pancreatic infiltrate (r=0.26, p<0.05) and fat necrosis (r=0.28, p<0.05), whereas Gal-3 correlated with pancreatic infiltrate (r=0.41, p<0.0005), pancreatic acinar necrosis (r= 0.38, p<0.001), and fat necrosis (r=0.30, p<0.01). Neither Gal-1 nor Gal-3 was associated with the degree of pancreatic edema. We conclude that diet-induced obesity increases the inflammation-associated markers Gal-1 and Gal-3, with variation over the time course of acute pancreatitis, and that these markers are correlated with pancreatic infiltration and necrosis. Supported by a grant from the National Pancreas Foundation and by NIH DK083328.
Background: Patterns of alcohol consumption have been considered to be important for the development of alcoholic liver disease but very limited data exist on the cumulative drinking pattern and volume of alcohol drinking over the lifetime in patients with alcohol induced pancreatitis. We aimed to determine the differences in drinking patterns between patients with alcohol induced pancreatitis and patients with alcohol dependence (AD). Methods: Patients with alcohol induced pancreatitis were examined and interviewed about alcohol drinking patterns during an outpatient visit. Patients with AD, currently in treatment for AD (without clinical or laboratory evidence of pancreatic disease) were matched for gender and age (+/- 5 years) with the group with alcohol induced pancreatitis. At the interview, the Lifetime Drinking History (LDH) questionnaire, a detailed and validated questionnaire was used (Koenig et al J Stud Alcohol Drugs 2009). This instrument about lifetime drinking habits, allows calculation of the lifetime alcohol intake in units of alcohol, drinking days, drinks per drinking day and binge drinking. Alcohol Dependence was assessed using DSMIV criteria for AD. Results: A total of 37 patients with alcohol induced pancreatitis (31 males and 6 females; median age 58 (IQR 46-62) and 37 AD patients (27 males and 10 females; median age; 56 (52-68) were included. Overall 26/34 (76%) patients with alcohol induced pancreatitis fulfilled the criteria for alcohol dependence and all AD (100%) patients (p= 0.017). The onset age for alcohol drinking was similar 16 (15-18) vs 15 (14-18) and duration of alcohol consumption, 38 years (28-43) vs. 37 (26-41) (NS), in the two groups. The number of drinking days was higher in the alcohol induced pancreatitis patients than in AD: 3870 (2011-7213) vs. 3580 (2069-4423) (p=NS). The lifetime alcohol intake was 35326 units (16369-79399) vs. 43688 units (14235-75763) (NS) and drinks per drinking day were 10 (6-16) vs. 13 (7-21) (NS). No significant difference was found in binge drinking between the groups. Conclusions: The total lifetime alcohol intake and pattern of alcohol consumption seems to be similar in patients with alcohol induced pancreatitis and those with alcohol dependence without pancreatitis. The pattern of alcohol consumption does not seem to play a major role in the development of alcohol induced pancreatitis. A significant proportion of patients with alcohol induced pancreatitis do not fulfill the criteria for alcohol dependence.
Sa1479 Leukotriene B4 Activation of TRPV1 Mediates Acute Pancreatitis Induced by Pancreatic Duct Infusion of Sodium Taurocholate in Mice Rafiq A. Shahid, Steven R. Vigna, Rodger A. Liddle Background: Retrograde perfusion of the pancreatic duct with bile salts causes acute pancreatitis of the head of the pancreas. We have previously shown that other causes of acute pancreatitis such as secretagogue hyperstimulation, ligation of the common pancreaticobiliary duct, or retrograde perfusion of the pancreatic duct by ERCP contrast medium are mediated by the transient receptor potential vanilloid-1 receptor (TRPV1) in rats and mice. In the present work we evaluated the role of TRPV1 and its endogenous agonist ligand, leukotriene B4 (LTB4), in acute pancreatitis caused by perfusion of the pancreatic duct by a bile salt. Methods: Acute inflammation of the pancreas was stimulated by retrograde perfusion of the main pancreatic duct with 2% sodium taurocholate (NaT) at a rate of 5 μl/min for 10 minutes in both wild type and TRPV1 knockout mice. The mice were killed 24 hours later and the pancreas was weighed and harvested for subsequent myeloperoxidase (MPO) assay, LTB4 assay, and histopathological analysis. Blood was also collected for serum amylase measurement. Results: Retrograde pancreatic ductal infusion of NaT for 10 min caused significant increases in serum amylase levels, pancreatic edema, pancreatic MPO and LTB4 levels, and histopathology (P < 0.001 vs vehicle controls) 24 hours later. When the pancreatic ducts of wild type mice were perfused with 2% NaT containing 14 μg/ml resiniferatoxin (RTX), a TRPV1 excitotoxin that desensitizes TRPV1 at high concentrations, significant reductions in serum amylase levels (62%), pancreatic edema (84%), pancreatic MPO levels (96%), and histopathology (77%) were observed (P < 0.01-0.001) vs NaT alone. Similarly, retrograde perfusion of the pancreatic duct of TRPV1 knockout mice with 2% NaT resulted in significantly reduced (P <0.001) pancreatic MPO levels (86%) and histopathology (68%); serum amylase and pancreatic edema were not reduced. To assess the role of the endogenous TRPV1 agonist ligand, LTB4, in bile salt-induced pancreatic inflammation, wild type mice were pretreated with an ip injection of 10 mg/kg MK 886, an inhibitor of LTB4 biosynthesis. MK 886 pretreatment also significantly reduced pancreatic edema (66%; P < 0.05), pancreatic MPO (66%; P < 0.001), pancreatic LTB4 (30%; P < 0.01), and histopathology (77%; P < 0.001) in response to NaT. Conclusions: We conclude that intraductal bile salts cause production of LTB4 in the pancreas which subsequently activates TRPV1 on primary sensory nerves to elicit some of the features of acute pancreatitis.
Sa1477 Cardiovascular Disease and Risk of Acute Pancreatitis in a Population-Based Study Tomas S. Bexelius, Rickard Ljung, Fredrik Mattsson, Jesper Lagergren Background: The increasing incidence of acute pancreatitis remains to be explained. The low-grade inflammation that characterises cardiovascular disorders could facilitate the development of pancreatitis. The aim of this study was to clarify the association between cardiovascular disorders and acute pancreatitis. Methods: A nested population-based case-control study was conducted in Sweden from 2006 through 2008. Cases had a first episode of acute pancreatitis diagnosed in the nationwide Patient Register. Control subjects were matched on age, sex and calendar year, and randomly selected from all Swedish residents (40-84 years old) as recorded in the Register of the Total Population. Exposure to cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure and stroke) was identified in the Patient Register. Relative risk of acute pancreatitis was estimated by odds ratios (OR) with 95% confidence intervals (CI) using logistic regression adjusting for confounders (sex, age, calendar year, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases). Results: The study included 6,161 cases and 61,637 control subjects. Cardiovascular disorders were positively associated with acute pancreatitis (adjusted OR 1.34, 95% CI 1.25-1.44). When analyzed separately, hypertension (OR 1.38, 95% CI 1.28-1.49) and ischemic heart disease (OR, 1.14, 95% CI 1.04-1.24) showed positive associations with acute pancreatitis. There was no positive association observed for congestive heart failure (OR 1.09, 95% CI 0.961.23), or stroke (OR 0.81, 95% CI, 0.71-0.92). Conclusion: This population-based study indicates an association between cardiovascular disease and acute pancreatitis. Specifically, ischemic heart disease and hypertension seem to increase the risk of acute pancreatitis, whereas no such association was seen for congestive heart failure or stroke. Further research is needed to determine causality. Table 2. Prevalence of cardiovascular disorders and relative risk for acute pancreatitis, estimated by odds ratios (OR) with 95% confidence intervals (CI), in a nested case-control study in Sweden
Sa1480 Prolonged Severe Hypercalcemia Induces an Acute Pancreatitis in Rats, and Shortening of QTc Interval and Prolongation of Pq Interval. the Effect of the Therapy With Stable Gastric Pentadecapeptide BPC 157 (PL 14736) Ivan Barisic, Bozo Radic, Robert Klicek, Marko Sever, Spomenko Ilic, Vide Bilic, Lidija Berkopic, Ivan Dobric, Igor Petrovic, Luka Brcic, Iva Brcic, Danijela Kolenc, Martina Lovric-Bencic, Zeljko Romic, Sven Seiwerth, Predrag Sikiric Prolonged severe hypercalcemia induces an acute pancreatitis in rats, and shortening of QTc interval and prolongation of PQ interval. For counteraction, we propose the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in trials for inflammatory bowel disease (PL 14736, Pliva) and various wound treatment, no toxicity reported) that recovered acute pancreatitis as well as arrhythmias in rats (Dig Dis Sci, 1996, J Pharm Sci, 2003). Materials and methods: Rats received CaCl solution (200
AGA Abstracts
S-316
of these patients and 2 developed collections in areas not specifically drained by the indwelling trans-enteric stents. No patients required surgery or developed PCF. CONCLUSIONS The stated therapeutic goals of combined endoscopic and percutaneous drainage of WOPN- single-digit mortality, absence of PCF and avoidance of surgery- are durable in a large cohort of patients over a long period of follow-up. Recurrent pancreatic fluid collections are seen and, when symptomatic, are amenable to endoscopic or percutaneous drainage.
All estimates are adjusted for sex, age, calendar year, education, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases Sa1478 Serum Galectin -1 and Galectin-3 are Increased in Diet-Induced Obesity and Associated With Infiltrate and Necrosis in Experimental Acute Pancreatitis in Mice Maria Pini, Elise Malecki, Davina H. Rhodes, Karla J. Castellanos, Robert J. Cabay, Douglas R. Thompson, Giamila Fantuzzi
Sa1476 Lifetime Alcohol Intake and Pattern of Alcohol Consumption in Patients With Alcohol Induced Pancreatitis Einar Bjornsson, Jon K. Nielsen
The severity of acute pancreatitis is increased in obese individuals, and the mechanisms by which obesity predisposes toward inflammation are under study. Galectin-1 (Gal-1) and galectin-3 (Gal-3) are involved in epithelial-stromal-immune cell interactions in inflammation. We hypothesized that Gal-1 and Gal-3 would be increased in obesity and with the severity of experimental acute pancreatitis. Male C57BL6 mice were fed either chow or highfat diet (60% kcal/fat) for 13 weeks beginning at 4 weeks of age to produce lean and dietinduced obese mice (DIO), respectively. At 17 weeks of age, lean and DIO mice received i.p. injections of IL-12 (125 ng/mouse) and IL-18 (750 ng/mouse), and were killed either without injections (time =0 days) or at 1, 3, 7, and 15 days post-injection. Effects of DIO and time on serum Gal-1 and Gal-3 levels were analyzed with two-way ANOVA. There were significant main effects of DIO for serum Gal-1 and Gal-3 (both p<0.001), with both measures consistently higher across time for DIO mice. There were also significant time main effects for both serum Gal-1 and Gal-3 (both p<0.01). For serum Gal-3 there was a DIO x time interaction (p<0.001), in that the lean mice experienced a quicker return to normal concentrations relative to the obese mice. In an additional analysis, Pearson correlation coefficients were obtained for serum galectins vs. histologic scores. Gal-1 correlated with the degree of pancreatic infiltrate (r=0.26, p<0.05) and fat necrosis (r=0.28, p<0.05), whereas Gal-3 correlated with pancreatic infiltrate (r=0.41, p<0.0005), pancreatic acinar necrosis (r= 0.38, p<0.001), and fat necrosis (r=0.30, p<0.01). Neither Gal-1 nor Gal-3 was associated with the degree of pancreatic edema. We conclude that diet-induced obesity increases the inflammation-associated markers Gal-1 and Gal-3, with variation over the time course of acute pancreatitis, and that these markers are correlated with pancreatic infiltration and necrosis. Supported by a grant from the National Pancreas Foundation and by NIH DK083328.
Background: Patterns of alcohol consumption have been considered to be important for the development of alcoholic liver disease but very limited data exist on the cumulative drinking pattern and volume of alcohol drinking over the lifetime in patients with alcohol induced pancreatitis. We aimed to determine the differences in drinking patterns between patients with alcohol induced pancreatitis and patients with alcohol dependence (AD). Methods: Patients with alcohol induced pancreatitis were examined and interviewed about alcohol drinking patterns during an outpatient visit. Patients with AD, currently in treatment for AD (without clinical or laboratory evidence of pancreatic disease) were matched for gender and age (+/- 5 years) with the group with alcohol induced pancreatitis. At the interview, the Lifetime Drinking History (LDH) questionnaire, a detailed and validated questionnaire was used (Koenig et al J Stud Alcohol Drugs 2009). This instrument about lifetime drinking habits, allows calculation of the lifetime alcohol intake in units of alcohol, drinking days, drinks per drinking day and binge drinking. Alcohol Dependence was assessed using DSMIV criteria for AD. Results: A total of 37 patients with alcohol induced pancreatitis (31 males and 6 females; median age 58 (IQR 46-62) and 37 AD patients (27 males and 10 females; median age; 56 (52-68) were included. Overall 26/34 (76%) patients with alcohol induced pancreatitis fulfilled the criteria for alcohol dependence and all AD (100%) patients (p= 0.017). The onset age for alcohol drinking was similar 16 (15-18) vs 15 (14-18) and duration of alcohol consumption, 38 years (28-43) vs. 37 (26-41) (NS), in the two groups. The number of drinking days was higher in the alcohol induced pancreatitis patients than in AD: 3870 (2011-7213) vs. 3580 (2069-4423) (p=NS). The lifetime alcohol intake was 35326 units (16369-79399) vs. 43688 units (14235-75763) (NS) and drinks per drinking day were 10 (6-16) vs. 13 (7-21) (NS). No significant difference was found in binge drinking between the groups. Conclusions: The total lifetime alcohol intake and pattern of alcohol consumption seems to be similar in patients with alcohol induced pancreatitis and those with alcohol dependence without pancreatitis. The pattern of alcohol consumption does not seem to play a major role in the development of alcohol induced pancreatitis. A significant proportion of patients with alcohol induced pancreatitis do not fulfill the criteria for alcohol dependence.
Sa1479 Leukotriene B4 Activation of TRPV1 Mediates Acute Pancreatitis Induced by Pancreatic Duct Infusion of Sodium Taurocholate in Mice Rafiq A. Shahid, Steven R. Vigna, Rodger A. Liddle Background: Retrograde perfusion of the pancreatic duct with bile salts causes acute pancreatitis of the head of the pancreas. We have previously shown that other causes of acute pancreatitis such as secretagogue hyperstimulation, ligation of the common pancreaticobiliary duct, or retrograde perfusion of the pancreatic duct by ERCP contrast medium are mediated by the transient receptor potential vanilloid-1 receptor (TRPV1) in rats and mice. In the present work we evaluated the role of TRPV1 and its endogenous agonist ligand, leukotriene B4 (LTB4), in acute pancreatitis caused by perfusion of the pancreatic duct by a bile salt. Methods: Acute inflammation of the pancreas was stimulated by retrograde perfusion of the main pancreatic duct with 2% sodium taurocholate (NaT) at a rate of 5 μl/min for 10 minutes in both wild type and TRPV1 knockout mice. The mice were killed 24 hours later and the pancreas was weighed and harvested for subsequent myeloperoxidase (MPO) assay, LTB4 assay, and histopathological analysis. Blood was also collected for serum amylase measurement. Results: Retrograde pancreatic ductal infusion of NaT for 10 min caused significant increases in serum amylase levels, pancreatic edema, pancreatic MPO and LTB4 levels, and histopathology (P < 0.001 vs vehicle controls) 24 hours later. When the pancreatic ducts of wild type mice were perfused with 2% NaT containing 14 μg/ml resiniferatoxin (RTX), a TRPV1 excitotoxin that desensitizes TRPV1 at high concentrations, significant reductions in serum amylase levels (62%), pancreatic edema (84%), pancreatic MPO levels (96%), and histopathology (77%) were observed (P < 0.01-0.001) vs NaT alone. Similarly, retrograde perfusion of the pancreatic duct of TRPV1 knockout mice with 2% NaT resulted in significantly reduced (P <0.001) pancreatic MPO levels (86%) and histopathology (68%); serum amylase and pancreatic edema were not reduced. To assess the role of the endogenous TRPV1 agonist ligand, LTB4, in bile salt-induced pancreatic inflammation, wild type mice were pretreated with an ip injection of 10 mg/kg MK 886, an inhibitor of LTB4 biosynthesis. MK 886 pretreatment also significantly reduced pancreatic edema (66%; P < 0.05), pancreatic MPO (66%; P < 0.001), pancreatic LTB4 (30%; P < 0.01), and histopathology (77%; P < 0.001) in response to NaT. Conclusions: We conclude that intraductal bile salts cause production of LTB4 in the pancreas which subsequently activates TRPV1 on primary sensory nerves to elicit some of the features of acute pancreatitis.
Sa1477 Cardiovascular Disease and Risk of Acute Pancreatitis in a Population-Based Study Tomas S. Bexelius, Rickard Ljung, Fredrik Mattsson, Jesper Lagergren Background: The increasing incidence of acute pancreatitis remains to be explained. The low-grade inflammation that characterises cardiovascular disorders could facilitate the development of pancreatitis. The aim of this study was to clarify the association between cardiovascular disorders and acute pancreatitis. Methods: A nested population-based case-control study was conducted in Sweden from 2006 through 2008. Cases had a first episode of acute pancreatitis diagnosed in the nationwide Patient Register. Control subjects were matched on age, sex and calendar year, and randomly selected from all Swedish residents (40-84 years old) as recorded in the Register of the Total Population. Exposure to cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure and stroke) was identified in the Patient Register. Relative risk of acute pancreatitis was estimated by odds ratios (OR) with 95% confidence intervals (CI) using logistic regression adjusting for confounders (sex, age, calendar year, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases). Results: The study included 6,161 cases and 61,637 control subjects. Cardiovascular disorders were positively associated with acute pancreatitis (adjusted OR 1.34, 95% CI 1.25-1.44). When analyzed separately, hypertension (OR 1.38, 95% CI 1.28-1.49) and ischemic heart disease (OR, 1.14, 95% CI 1.04-1.24) showed positive associations with acute pancreatitis. There was no positive association observed for congestive heart failure (OR 1.09, 95% CI 0.961.23), or stroke (OR 0.81, 95% CI, 0.71-0.92). Conclusion: This population-based study indicates an association between cardiovascular disease and acute pancreatitis. Specifically, ischemic heart disease and hypertension seem to increase the risk of acute pancreatitis, whereas no such association was seen for congestive heart failure or stroke. Further research is needed to determine causality. Table 2. Prevalence of cardiovascular disorders and relative risk for acute pancreatitis, estimated by odds ratios (OR) with 95% confidence intervals (CI), in a nested case-control study in Sweden
Sa1480 Prolonged Severe Hypercalcemia Induces an Acute Pancreatitis in Rats, and Shortening of QTc Interval and Prolongation of Pq Interval. the Effect of the Therapy With Stable Gastric Pentadecapeptide BPC 157 (PL 14736) Ivan Barisic, Bozo Radic, Robert Klicek, Marko Sever, Spomenko Ilic, Vide Bilic, Lidija Berkopic, Ivan Dobric, Igor Petrovic, Luka Brcic, Iva Brcic, Danijela Kolenc, Martina Lovric-Bencic, Zeljko Romic, Sven Seiwerth, Predrag Sikiric Prolonged severe hypercalcemia induces an acute pancreatitis in rats, and shortening of QTc interval and prolongation of PQ interval. For counteraction, we propose the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in trials for inflammatory bowel disease (PL 14736, Pliva) and various wound treatment, no toxicity reported) that recovered acute pancreatitis as well as arrhythmias in rats (Dig Dis Sci, 1996, J Pharm Sci, 2003). Materials and methods: Rats received CaCl solution (200
AGA Abstracts
S-316