- Email: [email protected]
Sa1381 Acute Pancreatitis in Iceland - A Prospective Population Based Study on Incidence, Aetiology, Severity and Complications
consumption in Manitoba has been tracked by the Manitoba Liquor Commission since 1997. These data were used to assess for temporal trends in alcohol consumption and relation to rates of AP. Results: Admissions for AP increased significantly from 1984-2009 (Figure 1), with crude rates of hospitalization for AP increasing from 31.7 (95% CI 28.5-35.2) in 1984 to 67.1 (95%CI 62.7-71.9) per 100,000 population in 2009 (p ,0.0001). No significant difference was found between male and females (p .0.05). Higher rates of pancreatitis correlated with increasing age with median yearly rates of 8.8, 33.0, 57.0, 120.5, and 179.6/ 100,000persons in 0-24yo, 25-39yo, 40-54yo, 55-69yo, 70-84yo and 85+ yo respectively (P,0.0001). In 1997, 1999, 2001,2003, 2005, 2007 and 2009, yearly per capita alcohol consumption was 72.1 L, 72.8 L, 73.4 L, 75.1 L, 90.9 L, 95.3 L, and 101.1 L respectively (p,0.001). In-hospital mortality rate of AP at 30 days and at any time during admission has decreased significantly over time with recent rates as low as 2.2% and 2.7% respectively (P,0.01 for trend) (Figure 2). Conclusion: Hospitalization rates for AP have increased more than 100% over the last 25 years. Older age appears to be associated with higher rates of admission for AP. The increasing rate of AP may be related to increasing alcohol consumption in the province. Further we have shown elsewhere that cholecystectomy rates have been stable over this time period. Despite increasing rates of AP, mortality related to AP appears to be decreasing over time. These results are similar to previously reported European data that shows increasing rates of AP related to increasing alcohol consumption and improved diagnostic modalities, with a similar decrease in AP related mortality due to improved inhospital management of AP.
Sa1379 Electronic Health Record (EHR) Information Is Useful to Predict Clinically Relevant Outcomes in Acute Pancreatitis (AP) Dhiraj Yadav, Melissa I. Saul, Georgios I. Papachristou, David C. Whitcomb, Shyam Visweswaran, Michael A. Dunn Background: Persistent organ failure (OF) has been identified as a strong predictor of clinical outcomes in AP. Presence of systemic inflammatory response syndrome (SIRS) helps in early prediction of ICU admission and OF. While administrative data are used widely to describe population distributions, the use of EHR data to predict outcomes in AP has not been well studied. We hypothesized that EHR data would be useful to predict clinically relevant outcomes in AP. Methods: Using diagnosis codes, we identified all unique patients with a primary discharge diagnosis of AP from 2000-2009 at the University of Pittsburgh Medical Center. Patients with no available previous history, prior acute or chronic pancreatitis, organ transplant, pre-existing renal failure (serum Cr ≥ 2 or dialysis), a pancreatic cancer diagnosis [within 6 months], transfers from other institutions, and in whom SIRS data could not be retrieved by EHR were excluded. Information was retrieved using the EHR on demographic factors, etiology (using associated diagnoses codes), presence of SIRS (score of ≥2) on day 1, ICU admission, persistent OF (ICU admission ≥48 hours or serum Cr ≥2 mg/dl for ≥48 hours or dialysis), length of stay (LOS) and mortality (within 7 days, 30 days, or 90 days). The prevalence and risk of persistent OF and mortality based on SIRS and ICU admission were determined after controlling for confounding factors. Results: The mean age of patients (n=502) was 58 ± 18 years, 56% were female, 80% were White, mean Charlson co-morbidity score was 5.2 ± 1.9 and median LOS was 6.8 days. Common etiologies were biliary (40%), idiopathic (26%) or alcohol (8%). Overall prevalence of SIRS on day 1, ICU admission ≥48 hours, and persistent OF was 38%, 11% and 13% respectively. Mortality within 7 days, 30 days and 90 days of admission was 1%, 1.2% and 2% respectively. The risk of ICU admission, persistent OF and mortality increased progressively with an increase in SIRS score from 04 (p,0.05) and when evaluated as ,2 or ≥2 (Table 1). On multivariable logistic regression (Table 2), the presence of SIRS significantly increased the risk of ICU admission ≥48 hours, persistent OF and mortality after controlling for age, gender, race, co-morbidity and etiology. Risk of mortality increased significantly with prolonged ICU admission (Tables 1-2). The Charlson co-morbidity score was also a significant predictor for all outcomes while increasing age predicted mortality (p,0.05) and had borderline association with persistent OF (p= 0.06) and ICU admission ≥48 hours (p=0.08). Conclusions: EHR data provide robust prediction of clinically relevant outcomes in AP, and present a unique opportunity to study short- and long-term outcomes and resource utilization in AP. Incorporating identification of pancreatic necrosis by natural language processing will further enhance EHR utility. Table 1. Prevalence of ICU admission, Persistent OF and mortality based on presence of SIRS
Sa1381 Acute Pancreatitis in Iceland - A Prospective Population Based Study on Incidence, Aetiology, Severity and Complications Einar Bjornsson, Hanna Vidarsdottir, Pall H. Möller
Table 2. Predictive value of SIRS and ICU admission for outcomes of interest
Background: Prospective and population based studies on acute pancreatitis are limited. In a previous study, the incidence of acute pancreatitis was 32 per 100,000 inhabitants in Iceland, with gallstones (42%) and alcohol (32%) as the main etiologies (Birgisson H et al. Eur J Surg 2002). In the last decades alcohol consumption has increased in Iceland from: 3 L per capita older than 15 years of age in 1980, to 6 L per capita in 1999 and 8 L per capita in 2010. We aimed to determine whether alcohol induced acute pancreatitis has increased by comparison with the results of the previous study undertaken in Iceland. Methods: A prospective population based study of patients 18 years of age that were diagnosed with acute pancreatitis (AP) and hospitalized at the National University Hospital of Iceland from October 1st 2010 to September 30th 2011. Information was obtained on gender, age, symptoms, aetiology and complications. The criteria for AP were two of the following: 3x upper limit of normal of amylase/lipase, abdominal pain, imaging features compatible with AP. Main outcome measures for severity were Ranson and Imrie criteria as well as CRP values. Results: During the study period a total of 134 patients were diagnosed with acute pancreatitis, 78 males (58%), median age 57 years (IQR, 42-71). Overall 119/134 (89%) patients had their first attack of pancreatitis giving the estimated crude incidence of 53/ 100,000 inhabitants and year, which was not significantly higher than in the previous study. The causes were: gallstones in 52 cases (47%), alcohol 29 (23%), post ERCP in 12 (9.5%), medications in 10 (8%), idiopathic in 15 (12%) and miscellaneous (5.5%). Median age of patient with gallstone-pancreatitis was 63 years (IQR 48-78) and alcohol induced pancreatitis 51 year (IQR 42-67) (p=0.004). Gallstone induced pancreatitis was similar in females and males (27 vs. 26) whereas alcohol caused more pancreatitis in males (29 vs. 4), p=0.009. Amylase was higher at baseline in gallstone than in alcohol induced pancreatitis, 1173 (3572568) vs. 241 (161-489), p=0.0075). Twenty patients (16%) had Ranson scores of ≥ 3, 13 patients (10%) had Imrie scores of ≥ 3, and 47% had CRP concentrations .210 mg/L
Sa1380 Trends in Incidence and Mortality of Acute Pancreatitis Requiring Hospitalization: A Population-Based Study Dana C. Moffatt, Stephen Ip, Yichun Wei, B. Nancy Yu, Charles N. Bernstein Objectives: To determine the incidence and mortality rates related to acute pancreatitis (AP) requiring hospitalization in the entire province of Manitoba, Canada between 1984-2009. Trends in hospitalization and mortality rates and characteristics of this population will also be evaluated. Methods: Manitoba Health (MH) is the single health insurer of all individuals in Manitoba and all outpatient and inpatient physician-patient interactions are recorded in administrative databases since 1984. All patient contacts are recorded through a unique personal health identification number and coded using ICD-9 (1984-2004) and ICD-10 coding (2004-present). Demographic data of patients including age, gender, and geographic location, were obtained from the MH Registry file. AP was defined as any hospitalization with an ICD9 or 10 code for AP of any type. Death is registered in MH administrated databases by an end date of enrollment. Mortality related to AP was assessed within 30 days and at any time during admission to hospital. Population-based data on per capita alcohol
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The overall mortality rate was 0.2%. Five percent (107/2197) of patients had severe pancreatitis. Independent predictors of severe pancreatitis include age . 55 (OR, 1.6; P , 0.04), male gender (OR, 1.5; P ,0.05), white blood cell count .16,000 cells/mm3 (OR, 2.7; P ,0.01), serum glucose .200 mg/dL (OR, 2.1; P ,0.02) and serum calcium ,8 mg/dL (OR, 6.3; P,0.01). Conclusions: Compared to other recent population-based epidemiologic studies, we report a higher incidence of AP (1.0 vs. 0.6 per 1,000), less severe pancreatitis (5% severity) and lower mortality (0.2%). Independent predictors of severe pancreatitis include age .55, male gender, elevated wbc, elevated glucose and decreased serum calcium, which have been validated in other studies.
AGA Abstracts
during the first 4 days or .120 mg/L during the first week. Six patients had severe complications, three patients had pancreas necrosis, two had pseudocysts and one developed renal failure. One of those patients was admitted to intensive care unit. No patient died of acute pancreatitis during the study period. Conclusions: Incidence of acute pancreatitis in Iceland has not increased significantly compared with a study undertaken 10 years ago. Particularly, the incidence of alcohol induced pancreatitis has not increased despite increased alcohol consumption in Iceland. Acute pancreatitis in a population based setting had an overall good prognosis.
Sa1676 Estrogens Promote Development of Colitis-Associated Cancer Jarom Heijmans, Mattheus C. Wielenga, Sanne Rosekrans, Jooske F. van Lidth de Jeude, Joris J. Roelofs, Patrick Groothuis, Antwan Ederveen, Eveline S. de Jonge Muller, Izak Biemond, James C. Hardwick, Daniel W. Hommes, Vanesa Muncan, Gijs R. van den Brink Background and Aim In patients with inflammatory bowel diseases the risk of colorectal cancer (CRC) is up to 6 fold increased compared to the general population. The sequence of mutations that drives colitis associated colorectal carcinogenesis is distinct from the sporadic adenoma to carcinoma sequence and factors that influence its initiation and progression are poorly defined. The Women's Health Initiative studies have clearly established that female hormones protect against sporadically occurring CRC. Recently, it was shown that postmenopausal hormonal replacement increases the risk for developing inflammatory bowel disease. We therefore set out to determine the influence of female hormones on colitis associated colorectal carcinogenesis. Methods We studied colitis-associated cancer using a model that combines treatment with dextran sodium sulphate (DSS) and azoxymethane (AOM). Female mice were subjected to ovariectomies or sham operations and supplemented with placebo, estradiol (E2), the progestin medroxyprogesterone acetate (MPA) or a combination of both. We used estrogen receptor (ER) -alpha and -beta mutant mice to examine the role of these receptors in colitis-associated cancer development. Results Females that had undergone ovariectomy were markedly protected from tumor development compared to sham operated mice (7.0 vs. 12.0 polyps per colon, P , 0.001). hormone replacement with MPA alone did not affect tumorigenesis in ovariectomized mice. Mice that received E2 showed a dramatic increase in polyp development compared to placebo treated mice (16.0 vs. 1.5 polyps per colon, P , 0.001). Besides increased numbers of polyps, E2 also strongly promoted tumor progression with all E2 treated animals developing at least one invasive adenocarcinoma whereas placebo treated animals developed adenomas only. E2 treated animals showed an aggravated response to DSS with increased production of Il-6 and enhanced epithelial proliferation 5 weeks after the last cycle of DSS. Using estrogen receptor (Er) mutant mice we find that protumorigenic effect of estrogen depends on both Er-alpha and Er-beta. Conclusion Female hormones promote colitis associated tumorigenesis. We identify estradiol as the factor responsible for this effect. DSS induced colitis as well as colitis-associated tumors are aggravated by estradiol. We find that tumorigenesis is influenced by both estrogen receptors alpha and beta. Our findings suggest that estrogens promote inflammation associated cancer development by impairing the mucosal response to inflammatory damage.
Sa1382 Differences in Outcomes Among Patients With Post-ERCP Pancreatitis and Alcohol-Induced Acute Pancreatitis Mehak Idrees, Ayesha Kamal, Izzah Vasim, Eun Ji Shin, Venkata S. Akshintala, Ali Kord Valeshabad, Payal Saxena, Vikesh K. Singh, Anne Marie Lennon, Marcia I. Canto, Anthony N. Kalloo, Mouen Khashab Background: Acute pancreatitis is the most common complication of ERCP and occurs in 5-15% of procedures. Although post-ERCP pancreatitis (PEP) is most often mild, it is occasionally severe and can be a devastating illness with pancreatic necrosis, multiorgan failure, permanent disability and even death. Aims: To compare morbidity and mortality rates in patients with alcohol-induced pancreatitis (AP) and those with PEP. Methods: Acute pancreatitis was defined as a clinical illness with typical pancreatitis symptoms associated with serum amylase or lipase at least 3 times normal and/or imaging evidence of pancreatitis. PEP and AP patients admitted to a single academic tertiary care center between 6/2007 and 6/ 2012 were included in the study. Length of hospital stay (LOS), pancreas necrosis, pseudocyst formation, need for interventions to treat complications, organ failure as well as mortality rate were obtained for the two groups of patients. We used a t-test to compare LOS and univariate analysis to evaluate the remaining variables impacting outcomes. Results: During the study period, 328 patients had AP (mean age 47yrs, 38% female) and 58 patients had PEP (mean age 49 yrs, 67% female). Most common indications for ERCP in the PEP group were sphincter of Oddi dysfunction (n=10), recurrent acute pancreatitis (n=10) and biliary stones (n=5). The mean LOS was 5.26 days for PEP group and 5.51days for AP (P=0.76). In the PEP group, 62% of patients had prophylactic PD stent placed and LOS was 1-2 days in 22.6%, 3-10 days in 69.8%, and .10 days in 7.6% of patients. While 5 (8.6%) patients in PEP group had pseudocyst formation or pancreatic necrosis, this occurred in 86 (26.2%) patients in the AP group (OR 1.94, 95% CI 1.21-3.12, p=0.006). Organ failure (OR 1.12, 95% CI 0.65-1.93, p=0.68) and need for interventions (radiologic, endoscopic or surgical) for treatment of pancreatitis complications (OR 1.47, 95% CI 0.53-4.12, p=0.46) were more commonly required in AP patients, but the difference was not statistically significant. Finally, mortality rate was 0% in PEP and 2.44% (n=8) in AP group (p=0.61). Conclusion: Etiology of pancreatitis is an important determinant of the disease course. PEP seems to be a milder disease form of pancreatitis than AP. It is associated with decreased incidence of pancreatic necrosis and pseudocyst formation.
Sa1677 Integrin αVβ6 (ITGB6) Is a Novel Serum Tumor Marker in Colorectal Cancer (CRC) Patients and Is Associated With Invasion and Metastasis of CRC Susan Bengs, Marianne R. Spalinger, Silvia Lang, Lotta von Boehmer, Achim Weber, Stephan R. Vavricka, Pascal Frei, Alexander Knuth, Michael Fried, Gerhard Rogler, Michael Scharl Background: Colorectal carcinoma (CRC) is the third most frequent tumor entity worldwide and survival rates for metastatic CRC (mCRC) are poor. Therefore, markers for early diagnosis are urgently needed. A critical event in tumor invasion and metastasis is epithelial-mesenchymal-transition (EMT). Integrin αvβ6 (ITGB6) is expressed during EMT and associated with cell proliferation and invasiveness. Moreover, increased ITGB6 expression in primary CRC correlates with poor patient survival. Here, we investigated, whether ITGB6 tissue expression is associated with mCRC and can be used as a tumor marker for CRC diagnosis and EMT. Methods: Expression of ITGB6 and co-localization with matrix metalloproteinase 9 (MMP9) and fibronectin in liver metastasis (n=10) and primary tumors (n=10) of CRC patients were examined by immunohistochemistry (IHC). ITGB6 serum levels in well-characterized CRC patients (n=64) were assessed by ELISA. The correlation with clinical and pathological characteristics was analyzed. mRNA levels were assessed by real-time RT-PCR in HT29intestinal epithelial cells (IEC). Results: By IHC, we found considerable ITGB6 staining along the invasion front of primary CRC tissue and the CRC metastasis in liver. IHC revealed co-expression of ITGB6 stained cells with MMP9, which is activated by ITGB6, as well as with fibronectin, the ligand of ITGB6, at the invasion front. ITGB6 was detectable in the serum of CRC patients showing a clear cut-off value of 4 ng/ml ITGB6. Higher serum levels were associated with worse survival (2.51±1.44 vs. 4.43±3.71 years). All of the patients with levels higher than 4 ng/ml ITGB6 revealed T-stage ≥ 2, G-stage ≥ 2, indicative for infiltrative and de-differentiated tumors, as well as 100 % metastatic disease (M). To assess, how ITGB6 expression is regulated, we treated HT29-IECs with tumor necrosis factor (TNF, 48 h), a known mediator of EMT and/or epidermal growth factor (EGF; 24 h). TNF-treatment resulted in increased mRNA levels of ITGB6 (p ,0.01), EGF receptor (EGFR; p,0.05), Ets1 transcription factor, the suggested regulator of ITGB6 (p ,0.01), as well as elevated vimentin (p,0.01), but decreased E-cadherin (p,0.001), indicating EMT. Stimulation with EGF resulted in decreased ITGB6 (p ,0.05) and E-cadherin (p,0.05), but increased EGFR (p,0.05) and vimentin (p,0.001) mRNA levels. EGF treatment of TNF-pretreated cells impaired the TNF-induced rise in ITGB6 (p ,0.01) and Ets-1 (p,0.05), but enhanced the EGFR mRNA level (p,0.05). Conclusions: In summary, we demonstrate that ITGB6 is strongly expressed at the invasion front of CRC primary tumors and metastases suggesting a crucial role for ITGB6 in CRC progression. Elevated ITGB6 serum levels correlate with poor survival and advanced TNM-stage indicating advanced disease and suggest the potential use of ITGB6 as a novel CRC serum tumor marker in clinical practice.
Sa1383 Preliminary Results of Pigtail Plastic Stent (PPS) and Fully Covered Self Expandable Metallic Stent (FCSEMS) Placement in the Endoscopic Treatment of Pancreatic Fluid Collections Orhan Kocaman, Hakan Senturk, Birol Baysal, Ali T. Ince, Ahmet Danalioglu, Mukaddes Tozlu, Ercan Kocakoc Background: Pancreatic fluid collections (PFCs) are usually treated endoscopically when it is needed. Preference of fully covered self expandable metal stents (FCSEMS) over pigtail plastic stents (PPS) is controversial Objective: To analyze the safety and efficacy of endosonography (EUS)-guided FCSEMS placement in comparison to PPS in the treatment of PFCs Methods: A total of 18 patients were included in the study between May 2011 and September 2012. First a 19G needle was introduced followed by insertion of 0.035 guide-wire and replacement of needle with a needle knive (NK). In case NK catheter slide through the hole spontaneously, electrical current was not administered. Bougie dilation with a graded 5-10 F catheter was followed with insertion of PPS (10F, 5-10 cm) or FCSEMS (6 cm or 8 cm in length and 10 mm in diameter). The patients were evaluated after 4 and 8 weeks and the latter was regarded as the final response. Student's t-test was used to compare the means of two samples. P,0.05 was accepted statistically significant. Statistical analyses were conducted using the SPSS (Version 12.0) statistical software program (SPSS, Chicago, IL, USA). Results: Eleven males and 7 females were recruited in the study. The mean age + SD of the patients was 49 ± 14 (20-71) years. Eleven pseudocysts (PS) and 7 walled-off necrosis (WON) were treated. Thirteen PPS and 5 FCSEMS were placed (all WON) at initial stage and PSs were replaced by FCSEMS due to inadequate drainage in four patients (2 WON and 2PS). One PPS migrated into the cyst during deployment and was retrieved after dilation of the tract with 16 mm balloon with insertion of gastroscope into the PFC. In one patient FCEMS was clogged and opened with ballon extractor, and for one 10F naso-bilary catheter was introduced to fasten recovery. No major complication was encountered. One FCSEMS was found migrated into the stomach. It was retrieved and another one was placed. The mean size of all cysts drained by PPS decreased from 131 mm (range:60-220 mm) to 92 mm (range: 40-150 mm; p.0.05) at 1-month follow up control. The mean size of all cysts drained by FCSEMS decreased from 118 mm (range:83-180 mm) to 50 mm (21-90 mm; p,0.05) at 1-month follow up control. The average procedural time for placing PPS (range: 30-55 minutes, mean: 44 minutes) was longer compared to those for placing FCSEMS (range: 25-42 minutes, mean:36 minutes; p ,0.05). Conclusion: FCSEMS is more effective than PPS in PFCs, especially in WON. Procedural time is shorter and recovery is rapid.
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Sa1379 Electronic Health Record (EHR) Information Is Useful to Predict Clinically Relevant Outcomes in Acute Pancreatitis (AP) Dhiraj Yadav, Melissa I. Saul, Georgios I. Papachristou, David C. Whitcomb, Shyam Visweswaran, Michael A. Dunn Background: Persistent organ failure (OF) has been identified as a strong predictor of clinical outcomes in AP. Presence of systemic inflammatory response syndrome (SIRS) helps in early prediction of ICU admission and OF. While administrative data are used widely to describe population distributions, the use of EHR data to predict outcomes in AP has not been well studied. We hypothesized that EHR data would be useful to predict clinically relevant outcomes in AP. Methods: Using diagnosis codes, we identified all unique patients with a primary discharge diagnosis of AP from 2000-2009 at the University of Pittsburgh Medical Center. Patients with no available previous history, prior acute or chronic pancreatitis, organ transplant, pre-existing renal failure (serum Cr ≥ 2 or dialysis), a pancreatic cancer diagnosis [within 6 months], transfers from other institutions, and in whom SIRS data could not be retrieved by EHR were excluded. Information was retrieved using the EHR on demographic factors, etiology (using associated diagnoses codes), presence of SIRS (score of ≥2) on day 1, ICU admission, persistent OF (ICU admission ≥48 hours or serum Cr ≥2 mg/dl for ≥48 hours or dialysis), length of stay (LOS) and mortality (within 7 days, 30 days, or 90 days). The prevalence and risk of persistent OF and mortality based on SIRS and ICU admission were determined after controlling for confounding factors. Results: The mean age of patients (n=502) was 58 ± 18 years, 56% were female, 80% were White, mean Charlson co-morbidity score was 5.2 ± 1.9 and median LOS was 6.8 days. Common etiologies were biliary (40%), idiopathic (26%) or alcohol (8%). Overall prevalence of SIRS on day 1, ICU admission ≥48 hours, and persistent OF was 38%, 11% and 13% respectively. Mortality within 7 days, 30 days and 90 days of admission was 1%, 1.2% and 2% respectively. The risk of ICU admission, persistent OF and mortality increased progressively with an increase in SIRS score from 04 (p,0.05) and when evaluated as ,2 or ≥2 (Table 1). On multivariable logistic regression (Table 2), the presence of SIRS significantly increased the risk of ICU admission ≥48 hours, persistent OF and mortality after controlling for age, gender, race, co-morbidity and etiology. Risk of mortality increased significantly with prolonged ICU admission (Tables 1-2). The Charlson co-morbidity score was also a significant predictor for all outcomes while increasing age predicted mortality (p,0.05) and had borderline association with persistent OF (p= 0.06) and ICU admission ≥48 hours (p=0.08). Conclusions: EHR data provide robust prediction of clinically relevant outcomes in AP, and present a unique opportunity to study short- and long-term outcomes and resource utilization in AP. Incorporating identification of pancreatic necrosis by natural language processing will further enhance EHR utility. Table 1. Prevalence of ICU admission, Persistent OF and mortality based on presence of SIRS
Sa1381 Acute Pancreatitis in Iceland - A Prospective Population Based Study on Incidence, Aetiology, Severity and Complications Einar Bjornsson, Hanna Vidarsdottir, Pall H. Möller
Table 2. Predictive value of SIRS and ICU admission for outcomes of interest
Background: Prospective and population based studies on acute pancreatitis are limited. In a previous study, the incidence of acute pancreatitis was 32 per 100,000 inhabitants in Iceland, with gallstones (42%) and alcohol (32%) as the main etiologies (Birgisson H et al. Eur J Surg 2002). In the last decades alcohol consumption has increased in Iceland from: 3 L per capita older than 15 years of age in 1980, to 6 L per capita in 1999 and 8 L per capita in 2010. We aimed to determine whether alcohol induced acute pancreatitis has increased by comparison with the results of the previous study undertaken in Iceland. Methods: A prospective population based study of patients 18 years of age that were diagnosed with acute pancreatitis (AP) and hospitalized at the National University Hospital of Iceland from October 1st 2010 to September 30th 2011. Information was obtained on gender, age, symptoms, aetiology and complications. The criteria for AP were two of the following: 3x upper limit of normal of amylase/lipase, abdominal pain, imaging features compatible with AP. Main outcome measures for severity were Ranson and Imrie criteria as well as CRP values. Results: During the study period a total of 134 patients were diagnosed with acute pancreatitis, 78 males (58%), median age 57 years (IQR, 42-71). Overall 119/134 (89%) patients had their first attack of pancreatitis giving the estimated crude incidence of 53/ 100,000 inhabitants and year, which was not significantly higher than in the previous study. The causes were: gallstones in 52 cases (47%), alcohol 29 (23%), post ERCP in 12 (9.5%), medications in 10 (8%), idiopathic in 15 (12%) and miscellaneous (5.5%). Median age of patient with gallstone-pancreatitis was 63 years (IQR 48-78) and alcohol induced pancreatitis 51 year (IQR 42-67) (p=0.004). Gallstone induced pancreatitis was similar in females and males (27 vs. 26) whereas alcohol caused more pancreatitis in males (29 vs. 4), p=0.009. Amylase was higher at baseline in gallstone than in alcohol induced pancreatitis, 1173 (3572568) vs. 241 (161-489), p=0.0075). Twenty patients (16%) had Ranson scores of ≥ 3, 13 patients (10%) had Imrie scores of ≥ 3, and 47% had CRP concentrations .210 mg/L
Sa1380 Trends in Incidence and Mortality of Acute Pancreatitis Requiring Hospitalization: A Population-Based Study Dana C. Moffatt, Stephen Ip, Yichun Wei, B. Nancy Yu, Charles N. Bernstein Objectives: To determine the incidence and mortality rates related to acute pancreatitis (AP) requiring hospitalization in the entire province of Manitoba, Canada between 1984-2009. Trends in hospitalization and mortality rates and characteristics of this population will also be evaluated. Methods: Manitoba Health (MH) is the single health insurer of all individuals in Manitoba and all outpatient and inpatient physician-patient interactions are recorded in administrative databases since 1984. All patient contacts are recorded through a unique personal health identification number and coded using ICD-9 (1984-2004) and ICD-10 coding (2004-present). Demographic data of patients including age, gender, and geographic location, were obtained from the MH Registry file. AP was defined as any hospitalization with an ICD9 or 10 code for AP of any type. Death is registered in MH administrated databases by an end date of enrollment. Mortality related to AP was assessed within 30 days and at any time during admission to hospital. Population-based data on per capita alcohol
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The overall mortality rate was 0.2%. Five percent (107/2197) of patients had severe pancreatitis. Independent predictors of severe pancreatitis include age . 55 (OR, 1.6; P , 0.04), male gender (OR, 1.5; P ,0.05), white blood cell count .16,000 cells/mm3 (OR, 2.7; P ,0.01), serum glucose .200 mg/dL (OR, 2.1; P ,0.02) and serum calcium ,8 mg/dL (OR, 6.3; P,0.01). Conclusions: Compared to other recent population-based epidemiologic studies, we report a higher incidence of AP (1.0 vs. 0.6 per 1,000), less severe pancreatitis (5% severity) and lower mortality (0.2%). Independent predictors of severe pancreatitis include age .55, male gender, elevated wbc, elevated glucose and decreased serum calcium, which have been validated in other studies.
AGA Abstracts
during the first 4 days or .120 mg/L during the first week. Six patients had severe complications, three patients had pancreas necrosis, two had pseudocysts and one developed renal failure. One of those patients was admitted to intensive care unit. No patient died of acute pancreatitis during the study period. Conclusions: Incidence of acute pancreatitis in Iceland has not increased significantly compared with a study undertaken 10 years ago. Particularly, the incidence of alcohol induced pancreatitis has not increased despite increased alcohol consumption in Iceland. Acute pancreatitis in a population based setting had an overall good prognosis.
Sa1676 Estrogens Promote Development of Colitis-Associated Cancer Jarom Heijmans, Mattheus C. Wielenga, Sanne Rosekrans, Jooske F. van Lidth de Jeude, Joris J. Roelofs, Patrick Groothuis, Antwan Ederveen, Eveline S. de Jonge Muller, Izak Biemond, James C. Hardwick, Daniel W. Hommes, Vanesa Muncan, Gijs R. van den Brink Background and Aim In patients with inflammatory bowel diseases the risk of colorectal cancer (CRC) is up to 6 fold increased compared to the general population. The sequence of mutations that drives colitis associated colorectal carcinogenesis is distinct from the sporadic adenoma to carcinoma sequence and factors that influence its initiation and progression are poorly defined. The Women's Health Initiative studies have clearly established that female hormones protect against sporadically occurring CRC. Recently, it was shown that postmenopausal hormonal replacement increases the risk for developing inflammatory bowel disease. We therefore set out to determine the influence of female hormones on colitis associated colorectal carcinogenesis. Methods We studied colitis-associated cancer using a model that combines treatment with dextran sodium sulphate (DSS) and azoxymethane (AOM). Female mice were subjected to ovariectomies or sham operations and supplemented with placebo, estradiol (E2), the progestin medroxyprogesterone acetate (MPA) or a combination of both. We used estrogen receptor (ER) -alpha and -beta mutant mice to examine the role of these receptors in colitis-associated cancer development. Results Females that had undergone ovariectomy were markedly protected from tumor development compared to sham operated mice (7.0 vs. 12.0 polyps per colon, P , 0.001). hormone replacement with MPA alone did not affect tumorigenesis in ovariectomized mice. Mice that received E2 showed a dramatic increase in polyp development compared to placebo treated mice (16.0 vs. 1.5 polyps per colon, P , 0.001). Besides increased numbers of polyps, E2 also strongly promoted tumor progression with all E2 treated animals developing at least one invasive adenocarcinoma whereas placebo treated animals developed adenomas only. E2 treated animals showed an aggravated response to DSS with increased production of Il-6 and enhanced epithelial proliferation 5 weeks after the last cycle of DSS. Using estrogen receptor (Er) mutant mice we find that protumorigenic effect of estrogen depends on both Er-alpha and Er-beta. Conclusion Female hormones promote colitis associated tumorigenesis. We identify estradiol as the factor responsible for this effect. DSS induced colitis as well as colitis-associated tumors are aggravated by estradiol. We find that tumorigenesis is influenced by both estrogen receptors alpha and beta. Our findings suggest that estrogens promote inflammation associated cancer development by impairing the mucosal response to inflammatory damage.
Sa1382 Differences in Outcomes Among Patients With Post-ERCP Pancreatitis and Alcohol-Induced Acute Pancreatitis Mehak Idrees, Ayesha Kamal, Izzah Vasim, Eun Ji Shin, Venkata S. Akshintala, Ali Kord Valeshabad, Payal Saxena, Vikesh K. Singh, Anne Marie Lennon, Marcia I. Canto, Anthony N. Kalloo, Mouen Khashab Background: Acute pancreatitis is the most common complication of ERCP and occurs in 5-15% of procedures. Although post-ERCP pancreatitis (PEP) is most often mild, it is occasionally severe and can be a devastating illness with pancreatic necrosis, multiorgan failure, permanent disability and even death. Aims: To compare morbidity and mortality rates in patients with alcohol-induced pancreatitis (AP) and those with PEP. Methods: Acute pancreatitis was defined as a clinical illness with typical pancreatitis symptoms associated with serum amylase or lipase at least 3 times normal and/or imaging evidence of pancreatitis. PEP and AP patients admitted to a single academic tertiary care center between 6/2007 and 6/ 2012 were included in the study. Length of hospital stay (LOS), pancreas necrosis, pseudocyst formation, need for interventions to treat complications, organ failure as well as mortality rate were obtained for the two groups of patients. We used a t-test to compare LOS and univariate analysis to evaluate the remaining variables impacting outcomes. Results: During the study period, 328 patients had AP (mean age 47yrs, 38% female) and 58 patients had PEP (mean age 49 yrs, 67% female). Most common indications for ERCP in the PEP group were sphincter of Oddi dysfunction (n=10), recurrent acute pancreatitis (n=10) and biliary stones (n=5). The mean LOS was 5.26 days for PEP group and 5.51days for AP (P=0.76). In the PEP group, 62% of patients had prophylactic PD stent placed and LOS was 1-2 days in 22.6%, 3-10 days in 69.8%, and .10 days in 7.6% of patients. While 5 (8.6%) patients in PEP group had pseudocyst formation or pancreatic necrosis, this occurred in 86 (26.2%) patients in the AP group (OR 1.94, 95% CI 1.21-3.12, p=0.006). Organ failure (OR 1.12, 95% CI 0.65-1.93, p=0.68) and need for interventions (radiologic, endoscopic or surgical) for treatment of pancreatitis complications (OR 1.47, 95% CI 0.53-4.12, p=0.46) were more commonly required in AP patients, but the difference was not statistically significant. Finally, mortality rate was 0% in PEP and 2.44% (n=8) in AP group (p=0.61). Conclusion: Etiology of pancreatitis is an important determinant of the disease course. PEP seems to be a milder disease form of pancreatitis than AP. It is associated with decreased incidence of pancreatic necrosis and pseudocyst formation.
Sa1677 Integrin αVβ6 (ITGB6) Is a Novel Serum Tumor Marker in Colorectal Cancer (CRC) Patients and Is Associated With Invasion and Metastasis of CRC Susan Bengs, Marianne R. Spalinger, Silvia Lang, Lotta von Boehmer, Achim Weber, Stephan R. Vavricka, Pascal Frei, Alexander Knuth, Michael Fried, Gerhard Rogler, Michael Scharl Background: Colorectal carcinoma (CRC) is the third most frequent tumor entity worldwide and survival rates for metastatic CRC (mCRC) are poor. Therefore, markers for early diagnosis are urgently needed. A critical event in tumor invasion and metastasis is epithelial-mesenchymal-transition (EMT). Integrin αvβ6 (ITGB6) is expressed during EMT and associated with cell proliferation and invasiveness. Moreover, increased ITGB6 expression in primary CRC correlates with poor patient survival. Here, we investigated, whether ITGB6 tissue expression is associated with mCRC and can be used as a tumor marker for CRC diagnosis and EMT. Methods: Expression of ITGB6 and co-localization with matrix metalloproteinase 9 (MMP9) and fibronectin in liver metastasis (n=10) and primary tumors (n=10) of CRC patients were examined by immunohistochemistry (IHC). ITGB6 serum levels in well-characterized CRC patients (n=64) were assessed by ELISA. The correlation with clinical and pathological characteristics was analyzed. mRNA levels were assessed by real-time RT-PCR in HT29intestinal epithelial cells (IEC). Results: By IHC, we found considerable ITGB6 staining along the invasion front of primary CRC tissue and the CRC metastasis in liver. IHC revealed co-expression of ITGB6 stained cells with MMP9, which is activated by ITGB6, as well as with fibronectin, the ligand of ITGB6, at the invasion front. ITGB6 was detectable in the serum of CRC patients showing a clear cut-off value of 4 ng/ml ITGB6. Higher serum levels were associated with worse survival (2.51±1.44 vs. 4.43±3.71 years). All of the patients with levels higher than 4 ng/ml ITGB6 revealed T-stage ≥ 2, G-stage ≥ 2, indicative for infiltrative and de-differentiated tumors, as well as 100 % metastatic disease (M). To assess, how ITGB6 expression is regulated, we treated HT29-IECs with tumor necrosis factor (TNF, 48 h), a known mediator of EMT and/or epidermal growth factor (EGF; 24 h). TNF-treatment resulted in increased mRNA levels of ITGB6 (p ,0.01), EGF receptor (EGFR; p,0.05), Ets1 transcription factor, the suggested regulator of ITGB6 (p ,0.01), as well as elevated vimentin (p,0.01), but decreased E-cadherin (p,0.001), indicating EMT. Stimulation with EGF resulted in decreased ITGB6 (p ,0.05) and E-cadherin (p,0.05), but increased EGFR (p,0.05) and vimentin (p,0.001) mRNA levels. EGF treatment of TNF-pretreated cells impaired the TNF-induced rise in ITGB6 (p ,0.01) and Ets-1 (p,0.05), but enhanced the EGFR mRNA level (p,0.05). Conclusions: In summary, we demonstrate that ITGB6 is strongly expressed at the invasion front of CRC primary tumors and metastases suggesting a crucial role for ITGB6 in CRC progression. Elevated ITGB6 serum levels correlate with poor survival and advanced TNM-stage indicating advanced disease and suggest the potential use of ITGB6 as a novel CRC serum tumor marker in clinical practice.
Sa1383 Preliminary Results of Pigtail Plastic Stent (PPS) and Fully Covered Self Expandable Metallic Stent (FCSEMS) Placement in the Endoscopic Treatment of Pancreatic Fluid Collections Orhan Kocaman, Hakan Senturk, Birol Baysal, Ali T. Ince, Ahmet Danalioglu, Mukaddes Tozlu, Ercan Kocakoc Background: Pancreatic fluid collections (PFCs) are usually treated endoscopically when it is needed. Preference of fully covered self expandable metal stents (FCSEMS) over pigtail plastic stents (PPS) is controversial Objective: To analyze the safety and efficacy of endosonography (EUS)-guided FCSEMS placement in comparison to PPS in the treatment of PFCs Methods: A total of 18 patients were included in the study between May 2011 and September 2012. First a 19G needle was introduced followed by insertion of 0.035 guide-wire and replacement of needle with a needle knive (NK). In case NK catheter slide through the hole spontaneously, electrical current was not administered. Bougie dilation with a graded 5-10 F catheter was followed with insertion of PPS (10F, 5-10 cm) or FCSEMS (6 cm or 8 cm in length and 10 mm in diameter). The patients were evaluated after 4 and 8 weeks and the latter was regarded as the final response. Student's t-test was used to compare the means of two samples. P,0.05 was accepted statistically significant. Statistical analyses were conducted using the SPSS (Version 12.0) statistical software program (SPSS, Chicago, IL, USA). Results: Eleven males and 7 females were recruited in the study. The mean age + SD of the patients was 49 ± 14 (20-71) years. Eleven pseudocysts (PS) and 7 walled-off necrosis (WON) were treated. Thirteen PPS and 5 FCSEMS were placed (all WON) at initial stage and PSs were replaced by FCSEMS due to inadequate drainage in four patients (2 WON and 2PS). One PPS migrated into the cyst during deployment and was retrieved after dilation of the tract with 16 mm balloon with insertion of gastroscope into the PFC. In one patient FCEMS was clogged and opened with ballon extractor, and for one 10F naso-bilary catheter was introduced to fasten recovery. No major complication was encountered. One FCSEMS was found migrated into the stomach. It was retrieved and another one was placed. The mean size of all cysts drained by PPS decreased from 131 mm (range:60-220 mm) to 92 mm (range: 40-150 mm; p.0.05) at 1-month follow up control. The mean size of all cysts drained by FCSEMS decreased from 118 mm (range:83-180 mm) to 50 mm (21-90 mm; p,0.05) at 1-month follow up control. The average procedural time for placing PPS (range: 30-55 minutes, mean: 44 minutes) was longer compared to those for placing FCSEMS (range: 25-42 minutes, mean:36 minutes; p ,0.05). Conclusion: FCSEMS is more effective than PPS in PFCs, especially in WON. Procedural time is shorter and recovery is rapid.
AGA Abstracts
S-280