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T1302 Moderately Severe Acute Pancreatitis: A Prospective Validation Study of This New Subgroup of Acute Pancreatitis
higher in severe patients compared to mild on days 2-5. In those 38 patients (SAP n=9; MAP n=29) with a sample obtained within 72 hours of pain onset, a NGAL cut-off level of 125 ng/ml, revealed an area under the curve 89% (fig 1), sensitivity 88%, and specificity 90% (p-value <0.0001). Conclusions: In AP, NGAL serum levels are strongly associated with organ failure and disease severity. Elevated NGAL levels > 125 mng/ml early in the course of AP appear to accurately predict a severe course and warrants further study either alone or in combination with other biomarkers.
The Risk Factors and Clinical Outcome of Pancreatic Pseudocyst Developed After Acute Pancreatitis Tae Nyeun Kim, Kyeong Ok Kim, Byung-Ik Jang, Si Hyung Lee, Yong Gil Kim, Sung Bum Kim Background and aims: The incidence and clinical course of the pancreatic pseudocyst is expected to be changed due to the recent advance in various diagnosis and treatment modalities. The aims of this study were to analyze the incidence, risk factors and clinical outcome of pancreatic pseudocyst following acute pancreatitis. Patients and methods: We reviewed the medical records of the total 405 patients with acute pancreatitis admitted to Yeungnam University Hospital from January 2000 to December 2007. Acute pancreatitis caused by trauma, operation or endoscopic retrograde cholangiopancreatography(ERCP) was excluded in this study. The cause of pancreatitis, duration from symptom onset to admission, computed tomography(CT) grading, laboratory data and presence of recurrent pancreatitis or chronic pancreatitis were compared between patients with and without pseudocyst. Results: The mean age of the patients was 55.3±15.3 years and male to female ratio was 2.8:1. Among the 405 cases with acute pancreatitis, 55 cases had underlying chronic pancreatitis. Pancreatic pseudocyst was developed in 18.3% of the acute pancreatitis. The mean time from the diagnosis of pancreatitis to the detection of pseudocyst was 71.1±15.2 days. The locations of pseudocyst were 54.1% in pancreatic tail, 29.7% in head and 12.2% in body. The mean size of the pseudocyst was 3.7±2.2cm. Six patients required endoscopic(3 patients) and percutaneous(3 patients) drainage at the time of diagnosis and all patients improved. Of the 68 patients with conservative treatment, pseudocyst disappeared or decreased in size spontaneously in 39.7% and 35.3% of the cases respectively. Ten cases (14.7%) increased and 7 cases (10.3%) showed no change in size. In 10 cases with size increase, 3 cases improved with endoscopic intervention and 2 cases underwent surgical treatment. The other 5 patients with no symptoms were observed and 2 cases of them improved spontaneously. By multivariate analysis, the risk factors of pancreatic pseudocyst were the presence of underlying chronic pancreatitis, interval from symptom onset to visiting the hospital and alcoholic pancreatitis. The factor that could predict spontaneous resolution of the pseudocyst was single lesion. Conclusion: The incidence of pseudocyst after acute pancreatitis was 18.3%, and 71.2% of cases were improved spontaneously. Presence of the underlying chronic pancreatitis, alcoholic etiology and long interval from symptom onset to admission are risk factors of pseudocyst, and single lesion is the predictor of spontaneous resolution.
T1301 Serum Hydrogen Sulfide and Substance P Are Early Clinical Predictors of the Severity of Acute Pancreatitis Eric WL Wee, Madhav Bhatia, Mark L. Fernandes, Krishnakumar Madhavan, Jennie Y. Wong, Ai Ling Yeo, Min He, Siaw Wei Ng, Khek Yu Ho INTRODUCTION Treatment of acute pancreatitis (AP) is hampered by the absence of an early predictor of severity. Hydrogen sulfide (H2S) and substance P (SP) play important pro-inflammatory roles in mouse models of AP, but their roles in human AP have not been well studied. AIMS To prospectively evaluate the role of H2S and SP as early predictors of severity of AP in patients who present with this disease. METHODS Patients who presented with AP within 72 hours of onset of symptoms were included into this study. Blood for serum H2S and SP levels was obtained from the patients at 0, 6, 12, 24, 48 and 72 hours following entry into the study. Their levels were correlated with the severity of AP as determined by the Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Atlanta, and Ranson's criteria. RESULTS 35 subjects were evaluated. The mean age was 52 (±16) years old; and 24 (68.5%) were male. The etiology of AP included gallstones in 18 patients (51.4%), alcohol ingestion in 7 (20.0%), hypertriglyceridemia in 6 (17.1%), endoscopic retrograde cholangiopancreatography-induced in 3 (8.5%) and hypercalcemia in 1 (2.8%). AP was classified as severe in 15 (42.8%), 12 (34.2%), and 19 (54.2%) according to Ranson's, APACHE II and Atlanta criteria respectively. 3 (8.5%) developed organ failure, 2 (5.7%) pancreatic necrosis, and 8 (22.8%) pancreatic pseudocyst. Overall mortality was 1 (2.8%). H2S levels at 0-24 hours (Ranson's criteria: mild pancreatitis, 45.6 (±33.5) vs. severe, 194.5 (±162.3) μM, p=0.01; Atlanta criteria: mild, 34.3 (±21.1) vs. severe, 189.4 (±158.9) μM, p=0.004), and at 24-36 hours (Ranson's criteria: mild, 54.9 (±79.4) vs. severe, 212.23 (±189.64) μM, p=0.004; Atlanta criteria: mild, 59.6 (±89.2) vs. severe, 174.1 (±182.2) μM, p=0.048) from the onset of symptoms correlated significantly with both Ranson's and Atlanta criteria. H2S between 0-24 hours was also predictive of severity (mild 100.0 (±102.2) vs. severe 356.1 (±150.8) μM, p= 0.002) based on APACHE II criteria. While the SP levels at 0-24 hours from the onset of symptoms also correlated significantly with Ranson's criteria (mild, 1.62 (±2.39) vs. severe, 8.87 (±10.77) ng/ml, p=0.044), and Atlanta criteria (mild, 0.68 (±0.74) vs. severe 8.73 (±10.47) ng/ml, p=0.007), they did not correlate with APACHE II criteria (p=0.36). CONCLUSION This is the first study to suggest that H2S and SP are involved in the inflammatory response of AP in humans. H2S and SP levels correlated with the severity of AP at the early hours of onset of symptoms, indicating a potential role for these markers as early predictors of disease severity.
T1299 Erythrocyte Sedimentation Rate for Predicting Severity of Acute Pancreatitis Supot Pongprasobchai, Voravut Jianjaroonwong Background: Assessing the severity of acute pancreatitis (AP) is an important initial step in the management of AP. Ideal assessment tool should be simple and widely available. Creactive protein (CRP) remains one of the most popular, simple and accurate tool for predicting severity of AP. In developing countries, however, CRP is still not widely available. Erythrocyte sedimentation rate (ESR) is also an acute phase reactant. We investigated the utility of ESR for predicting severity of AP as compared to CRP. Method: All patients with AP presented during January 2008 to November 2008 were prospectively studied. ESR (Westergren method) and CRP (immunonephelometric method) were analyzed at admission and then every 12 hr for 48 hr after admission. Severity of AP was defined according to the Atlanta definition. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of ESR, CRP and combination of ESR/CRP in predicting severe AP were calculated. Results: Fifty patients with AP (16 severe, 34 mild) were enrolled. The aetiologies of AP were alcohol 32%, biliary 34%, post-ERCP 20%, miscellaneous 8% and idiopathic 6%. ESR was significantly higher in patients with severe AP compared to mild AP. The optimal cutoff level of ESR was 60 mm/hr. At 36 hr after admission, the sensitivity, specificity, PPV and NPV of ESR (>60 mm/hr) to predict severe AP were 73%, 59%, 48%, and 81%, respectively, compared to 87%, 87%, 76% and 93%, respectively by CRP (>150 mg/L). At 48 hr after admission, the results of ESR (> 60 mm/hr) were 81%, 60%, 52% and 86%, respectively, compared to 81%, 83%, 72% and 89%, respectively of CRP (>150 mg/L). The combination of either elevated ESR or CRP increased the sensitivity and NPV to predict severe AP to 100% and combination of elevated ESR and CRP increased the specificity and PPV to 97% and 90%, respectively in predicting severe AP at 36 hr after admission. Conclusion: ESR >60 mm/hr is useful for predicting severe AP. Although slightly inferior to CRP, ESR is simpler and more widely-available. The combination of ESR and CRP improved both sensitivity and specificity in predicting severe AP over CRP or ESR alone.
T1302 Moderately Severe Acute Pancreatitis: A Prospective Validation Study of This New Subgroup of Acute Pancreatitis Rupjyoti Talukdar, Santhi Swaroop Vege, Suresh T. Chari, Magdalen A. Clemens, Randall K. Pearson
T1300 Serum Neutrophil-Associated Gelatinase Lipocalcin (NGAL) Levels As An Early Biomarker of Severe Acute Pancreatitis Venkata Muddana, Georgios I. Papachristou, Subhankar Chakraborty, Sukhwinder Kaur, Neil Sharma, David C. Whitcomb, Randall Brand, Surinder K. Batra
Background and Aims: We have earlier described the entity of moderately severe acute pancreatitis (MSAP) (Am J Gastroenterol (In press)), characterized by presence local complications (i.e., pancreatic necrosis and/or fluid collections).without organ failure. MSAP patients meet criteria for severe acute pancreatitis (SAP) as defined by Atlanta criteria; however, their mortality is low and similar to that seen in mild acute pancreatitis (MAP) but they have prolonged hospital stay characteristic of SAP. Our aim was to validate the existence of the entity of MSAP in a prospectively identified cohort of patients with AP. Methods: We classified a prospective cohort of 82 AP patients directly admitted to Mayo Clinic Hospitals between 6/2004 and 8/2007 into 3 subgroups: (a) SAP: presence of organ failure with/ without local complications, (b) MSAP: presence of local complications without organ failure and (c) MAP: defined by no organ failure or local complications. The outcome variables studied were need for ICU care, ICU days, total hospital days, need for interventions and death. We compared continuous variables using t-test and nominal variables using Chi square test. Results: Patients in the 3 subgroups did not differ in age, gender, hematocrit at admission or body mass index. Patients with MSAP did not require ICU care and had no mortality despite presence of necrosis and hospital stay similar to those who had organ
Introduction: Acute pancreatitis (AP) is a common inflammatory disorder with 10-20% progressing to severe disease. Up to now there is no early biomarker identified to predict accurately the course of AP. Neutrophil associated gelatinase lipocalin (NGAL) is a glycoprotein released from neutrophils and other epithelial cells and is upregulated in cells under “stress”, e.g. from infection, inflammation, or neoplastic transformation. Based on a previous finding of significantly elevated NGAL levels in humans with AP compared to normal controls, the aim of this study was to determine whether NGAL serum levels predict severity in the early course of AP. Methods: NGAL serum levels were measured using an ELISA assay in a frozen serum samples from patients with AP collected on day 1-7 from the onset of pain. Severe AP was defined as the presence of failure in at least one organ (cardiovascular, renal or pulmonary) for > 48 hours. Comparisons were made using Mann-Whitney test. Receiver Operating Characteristics (ROC) curves, sensitivities and specificities were calculated. Results: NGAL levels were measured from a total of 44 patients with AP. 28 patients (64%) had mild AP and 16(36%) had severe AP. NGAL serum levels were significantly
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pseudocysts. On univariate analysis factors associated with pseudocyst formation following AP were male sex (OR-3.17; 95% CI 1.06-9.49), palpable mass (OR- 8.29; 95% CI 2.1135.18), blood sugar > 150mg% (OR- 4.68; 95% CI 1.57-13.95), a high CRP (AUROC 0.867:SE 0.093; 95% CI 0.684-1.050), necrosis (OR-7.01; 95% CI 2.31-21.28), AFC (OR9.34; 95% CI 3.02-28.90), ascites (OR-22.15; 95% CI 4.49-109.38), pleural effusion (OR5.44; 95% CI 1.67-17.73), higher grade of pancreatitis (Grade E/C OR-15.75; 95% CI 1.65150.14) and higher CTSI score (AUROC-0.813: SE 0.05; 95% CI 0.71-0.92). On multivariate analysis, male sex (p=0.024), a palpable mass (p=0.028), ascites (p=0.005) and a high CTSI score (p=0.013) were associated with formation of pseudocyst. Conclusion: This study shows that male sex, palpable mass, ascites and high CTSI score at admission can predict the development of pseudocyst following an attack of acute pancreatitis.
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failure (Table). The following parameters were found to be significantly less in the MAP group when compared to SAP: need for ICU care, total hospital days, local complications, organ failure, interventions and death. Conclusions: MSAP has been validated in this prospective cohort as an exclusive entity, different from SAP and MAP. Table: Comparison between patients with MAP and MSAP
T1305 Is Oral Re-Feeding While On Parenteral Narcotics Beneficial in Mild Acute Pancreatitis? Kathryn A. Repas, Brian C. Jacobson, Rachael S. Diamond, Darwin Conwell, Bechien Wu, Peter A. Banks Introduction: Optimal timing to initiate re-feeding following mild acute pancreatitis remains controversial. We have reported in a prospective, randomized, controlled trial that initiation of a low fat solid diet following mild acute pancreatitis appears to be safe, provides more calories than a clear liquid diet, and does not increase length of hospitalization [Clin. Gastro. Hepatol. 2007]. We excluded patients who were still receiving parenteral narcotics at the time of re-feeding. Aims: To determine the impact of parenteral narcotics on success of refeeding in patients with mild acute pancreatitis. Methods: This was a retrospective review of patients with mild acute pancreatitis who qualified for the prospective oral re-feeding study but were excluded specifically because they received parenteral narcotics at the time of re-feeding (i.e. within 6 hours of re-feeding). Comparisons were made between patients who were excluded (Group A) and patients who participated in the oral re-feeding study (Group B). Failure of re-feeding was defined as need to be made NPO and increased narcotic requirement after re-feeding. Statistical Analysis: Graphpad Prism 5.01 Software. Results: 45 patients received narcotics within 6 hours prior to being re-fed (Group A). There were no statistical differences in age or gender between this group and the 121 patients who participated in the re-feeding study (Group B). The mean pain score at the time of re-feeding was higher in Group A than Group B (3.75 vs. 1.1, t-test p<0.0001). Patients in Group A were more likely to be made NPO after re-feeding (19/45 (42%) vs. 13/121 (11%), Fisher exact test p<0.0001). In addition, patients in Group A were more likely to require narcotics after re-feeding (37/45 (82%) vs. 15/121 (12%), Fisher exact test p<0.0001). Group A was re-fed sooner than Group B (2.1 vs. 2.5 days, t-test p=0.0054). However, earlier re-feeding of Group A resulted in a prolongation of the length of stay after re-feeding(3.1 vs. 1.8 days, t-test p=0.0016). Total length of hospital stay between Group A and Group B showed no difference (5.9 vs 4.3 days, t-test p=0.3014). Conclusions: 1. Patients still receiving parenteral narcotics prior to re-feeding were more likely to fail re-feeding. 2. Re-feeding while still receiving parenteral narcotics did not decrease hospital stay. 3. Re-feeding while on parenteral narcotics may not be beneficial.
* Significant difference (p value <0.05) when compared vs SAP ** Significant difference (p value <0.05) when compared vs MSAP T1303 Acute Pancreatitis Requiring ICU Admission Associated with An Earlier and Milder Form of Metabolic Acidosis Mark Saxena, Daniel Blachman, Anthony J. Nici, Adnan Muhammad, Girish Prajapati, Capecomorin Pitchumoni Introduction: Ranson's criteria states that a serum bicarbonate (base) decrease of 4 meq/L 48 hours after admission contributes to diminished survival. A more recent study suggests that earlier metabolic acidosis at 0-24 hours after admission is associated with adverse outcomes. The retrospective analysis of 74 patients using “multiple logistic regression analysis showed that [among the 27 risk factors] only acidosis (pH<7.35) was associated with death” at 24 hours (1). Our study examines the role of early metabolic acidosis, defined by routinely measured bicarbonate level, in the need for ICU admission in acute pancreatitis. Methods: Subject data was retrospectively collected from five hospitals over two years. Included subjects had: A physician-determined diagnosis of acute pancreatitis, abdominal pain, and amylase and lipase levels three times above normal. Outcomes measures included: ICU admission, bacteremia, length of stay, and pancreatitis-related complications (e.g. psuedocyst). Subjects were excluded for one of five severe, chronic medical conditions (e.g. ESRD on dialysis). Metabolic acidosis was defined as a serum bicarbonate level less than 22 meq/ L. This represented a base deficit of 2 meq/L. Associations between prognostic and outcome measures were assessed using Fisher's chi square test, potentially logistic after adjusting for: age, sex, race, smoking and alcohol. Results: Among the 174 charts reviewed, 119 subjects met inclusion/exclusion criteria and had sufficient data for comparison analysis. Subjects in all groups were similar with regards to age and sex. Fisher's chi square analysis showed that serum bicarbonate <22 meq/L on admission was more closely associated with the need for ICU admission (OR = 4.61 95% CI 1.39, 15.30 P=0.017) than admission bicarbonate >22 meq/L. No significant associations were found between metabolic acidosis and bacteremia, complications, or length of stay. No deaths were reported among included subjects. Conclusions: A milder, earlier form of metabolic acidosis than described in Ranson's 48-hour criteria was associated with ICU admission. This may be an early marker for intensive care level supervision in acute pancreatitis. References: 1. Zhu AJ, Shi JS, Sun XJ. Risk factors influencing mortality of patients with severe acute pancreatitis within 24 hours after admission. Hepatobiliary Pancreat Dis Int. 2003;2:453-7. 2. Swaroop VS, Chari ST, Clain JE. Severe acute pancreatitis. JAMA. 2004; 291: 2865-8. 3. De Campos T, Braga CF, Kuryura L, Hebara D, Assef JC, Rasslan S. Changes in the management of patients with severe acute pancreatitis. Arq Gastroenterol. 2008; 45:181-5.
T1306 Multiplex Serum Marker Panel Accurately Predicts Systemic Complications of Acute Pancreatitis Georgios I. Papachristou, Venkata Muddana, Christopher J. Langmead, Gilles Clermont, David C. Whitcomb Background: The clinical course of acute pancreatitis (AP) remains difficult to predict prior to the development of organ dysfunction, because of the complex dynamics of interacting systems from the molecular to organ levels and the variability between human subjects. We hypothesize that a limited number of pathways link the initiation of the acute inflammatory response to organ dysfunction, and identification of optimal biomarkers of pathway activation will improve prediction of clinical endpoints and provide readout of treatment effectiveness. Aim: To combine statistical modeling with machine-learning approaches and test the above hypothesis using clinical information and biomarkers from the Severity of Acute Pancreatitis Study (SAPS-1). Methods: 21 commonly measured clinical variables were recorded and 26 serum biomarkers were measured. Severe AP was defined as 48 hours of persistent organ dysfunction. Machine learning algorithms ranked biomarkers by information gain with respect to the outcome and provided corresponding prediction accuracies and areas-under the receiver-operating curve (AUC). Predictions were validated by 10-fold cross-validation. Results: 185 patients were prospectively ascertained (mean age 53 years; 53% males), 39 of which were classified as severe AP (21%). Only three of the 21 common clinical variables yielded a cross-validated information gain >0.2: admission hematocrit (0.55), glucose (0.25) and AST (0.22). By using Naïve Bayes, their accuracy in predicting organ failure was 82% with AUC of 0.86. 93 serum samples collected from 59 subjects (severe, mild) on days 2 (n=5, 20), 3 (n=7, 20), 4 (n=8, 14) and 7 (n=8, 11) were analyzed for biomarkers. Optimal performance was achieved with a 5 biomarker panel including angiopoietin-2 (Ang-2), resistin, soluble TNF receptor-1 (TNF-R1), hepatocyte growth factor (HGF) and interleukin 8 (IL-8). Accuracy of the panel in predicting organ failure reached 96% on day 2 and 3 after onset of pain with AUC of 0.81 and 0.99, respectively. Conclusions: New methods of pattern analysis of early markers of AP improve the predictive accuracy of biomarker panels and may be useful in classifying patients into high- and low-risk groups.
T1304 Pseudocyst Formation in Acute Pancreatitis (AP): Prediction At Admission By Clinical, Biochemical and Radiological Parameters K. S. Poornachandra, Deepak K. Bhasin, Birinder Nagi, Saroj K. Sinha, Surinder S. Rana, Nusrat Shafiq, Rajesh Gupta, Mandeep Kang, Samir Malhotra, Kartar Singh Objective: To study clinical, biochemical & radiological parameters at admission that predict development of pseudocyst following AP. Methods: 75 consecutive patients with AP were prospectively enrolled & subjected to clinical & laboratory examination. Contrast enhanced computerized tomography (CECT) of abdomen done after day 3 of pain. Severity staged according to Balthazar Ranson grading and CT severity index (CTSI). Abdominal ultrasound repeated at 2nd and 4th week. At 4 weeks CECT repeated in symptomatic patients and if abdominal ultrasound showed a pseudocyst. Results: 10 patients were excluded and 65 patients (44 males) were finally studied. The median age was 37 (40.9 ± 15.5) years. Etiology of AP was alcohol in 24, gall stones in 18, both in 4, drugs in 4, pancreas divisum in 2, post ERCP in 1, trauma in 1 and idiopathic in 11 patients. At admission, palpable mass, blood sugar > 150 mg%, ascites and pleural effusion was present in 3 (4.6%), 41 (63.1%), 45 (69.23%), and 45 (69.23%) patients respectively. Acute fluid collections (AFC) were seen in 34 (52.31%) patients. Necrosis was noted in 38(58.46%) patients (<30% necrosis, 30-50% necrosis and >50% necrosis in 36.8%, 26.3% and 36.8% patients respectively). Grade A, B, C, D & E pancreatitis was present in 1.5%, 3.1%, 43.1%, 23.1% and 29.2% patients respectively. The mean CTSI score was 5.09±2.94. On follow up, 34 (52.3%) patients developed pseudocyst and majority (52.94%) had multiple pseudocysts. Of the 34 AFC noted on the initial imaging, 4 resolved by 2nd week and 12 new were noted in the 2nd week and of these, 8 resolved. Of 19 patients with grade E pancreatitis, 18 developed
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The Risk Factors and Clinical Outcome of Pancreatic Pseudocyst Developed After Acute Pancreatitis Tae Nyeun Kim, Kyeong Ok Kim, Byung-Ik Jang, Si Hyung Lee, Yong Gil Kim, Sung Bum Kim Background and aims: The incidence and clinical course of the pancreatic pseudocyst is expected to be changed due to the recent advance in various diagnosis and treatment modalities. The aims of this study were to analyze the incidence, risk factors and clinical outcome of pancreatic pseudocyst following acute pancreatitis. Patients and methods: We reviewed the medical records of the total 405 patients with acute pancreatitis admitted to Yeungnam University Hospital from January 2000 to December 2007. Acute pancreatitis caused by trauma, operation or endoscopic retrograde cholangiopancreatography(ERCP) was excluded in this study. The cause of pancreatitis, duration from symptom onset to admission, computed tomography(CT) grading, laboratory data and presence of recurrent pancreatitis or chronic pancreatitis were compared between patients with and without pseudocyst. Results: The mean age of the patients was 55.3±15.3 years and male to female ratio was 2.8:1. Among the 405 cases with acute pancreatitis, 55 cases had underlying chronic pancreatitis. Pancreatic pseudocyst was developed in 18.3% of the acute pancreatitis. The mean time from the diagnosis of pancreatitis to the detection of pseudocyst was 71.1±15.2 days. The locations of pseudocyst were 54.1% in pancreatic tail, 29.7% in head and 12.2% in body. The mean size of the pseudocyst was 3.7±2.2cm. Six patients required endoscopic(3 patients) and percutaneous(3 patients) drainage at the time of diagnosis and all patients improved. Of the 68 patients with conservative treatment, pseudocyst disappeared or decreased in size spontaneously in 39.7% and 35.3% of the cases respectively. Ten cases (14.7%) increased and 7 cases (10.3%) showed no change in size. In 10 cases with size increase, 3 cases improved with endoscopic intervention and 2 cases underwent surgical treatment. The other 5 patients with no symptoms were observed and 2 cases of them improved spontaneously. By multivariate analysis, the risk factors of pancreatic pseudocyst were the presence of underlying chronic pancreatitis, interval from symptom onset to visiting the hospital and alcoholic pancreatitis. The factor that could predict spontaneous resolution of the pseudocyst was single lesion. Conclusion: The incidence of pseudocyst after acute pancreatitis was 18.3%, and 71.2% of cases were improved spontaneously. Presence of the underlying chronic pancreatitis, alcoholic etiology and long interval from symptom onset to admission are risk factors of pseudocyst, and single lesion is the predictor of spontaneous resolution.
T1301 Serum Hydrogen Sulfide and Substance P Are Early Clinical Predictors of the Severity of Acute Pancreatitis Eric WL Wee, Madhav Bhatia, Mark L. Fernandes, Krishnakumar Madhavan, Jennie Y. Wong, Ai Ling Yeo, Min He, Siaw Wei Ng, Khek Yu Ho INTRODUCTION Treatment of acute pancreatitis (AP) is hampered by the absence of an early predictor of severity. Hydrogen sulfide (H2S) and substance P (SP) play important pro-inflammatory roles in mouse models of AP, but their roles in human AP have not been well studied. AIMS To prospectively evaluate the role of H2S and SP as early predictors of severity of AP in patients who present with this disease. METHODS Patients who presented with AP within 72 hours of onset of symptoms were included into this study. Blood for serum H2S and SP levels was obtained from the patients at 0, 6, 12, 24, 48 and 72 hours following entry into the study. Their levels were correlated with the severity of AP as determined by the Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Atlanta, and Ranson's criteria. RESULTS 35 subjects were evaluated. The mean age was 52 (±16) years old; and 24 (68.5%) were male. The etiology of AP included gallstones in 18 patients (51.4%), alcohol ingestion in 7 (20.0%), hypertriglyceridemia in 6 (17.1%), endoscopic retrograde cholangiopancreatography-induced in 3 (8.5%) and hypercalcemia in 1 (2.8%). AP was classified as severe in 15 (42.8%), 12 (34.2%), and 19 (54.2%) according to Ranson's, APACHE II and Atlanta criteria respectively. 3 (8.5%) developed organ failure, 2 (5.7%) pancreatic necrosis, and 8 (22.8%) pancreatic pseudocyst. Overall mortality was 1 (2.8%). H2S levels at 0-24 hours (Ranson's criteria: mild pancreatitis, 45.6 (±33.5) vs. severe, 194.5 (±162.3) μM, p=0.01; Atlanta criteria: mild, 34.3 (±21.1) vs. severe, 189.4 (±158.9) μM, p=0.004), and at 24-36 hours (Ranson's criteria: mild, 54.9 (±79.4) vs. severe, 212.23 (±189.64) μM, p=0.004; Atlanta criteria: mild, 59.6 (±89.2) vs. severe, 174.1 (±182.2) μM, p=0.048) from the onset of symptoms correlated significantly with both Ranson's and Atlanta criteria. H2S between 0-24 hours was also predictive of severity (mild 100.0 (±102.2) vs. severe 356.1 (±150.8) μM, p= 0.002) based on APACHE II criteria. While the SP levels at 0-24 hours from the onset of symptoms also correlated significantly with Ranson's criteria (mild, 1.62 (±2.39) vs. severe, 8.87 (±10.77) ng/ml, p=0.044), and Atlanta criteria (mild, 0.68 (±0.74) vs. severe 8.73 (±10.47) ng/ml, p=0.007), they did not correlate with APACHE II criteria (p=0.36). CONCLUSION This is the first study to suggest that H2S and SP are involved in the inflammatory response of AP in humans. H2S and SP levels correlated with the severity of AP at the early hours of onset of symptoms, indicating a potential role for these markers as early predictors of disease severity.
T1299 Erythrocyte Sedimentation Rate for Predicting Severity of Acute Pancreatitis Supot Pongprasobchai, Voravut Jianjaroonwong Background: Assessing the severity of acute pancreatitis (AP) is an important initial step in the management of AP. Ideal assessment tool should be simple and widely available. Creactive protein (CRP) remains one of the most popular, simple and accurate tool for predicting severity of AP. In developing countries, however, CRP is still not widely available. Erythrocyte sedimentation rate (ESR) is also an acute phase reactant. We investigated the utility of ESR for predicting severity of AP as compared to CRP. Method: All patients with AP presented during January 2008 to November 2008 were prospectively studied. ESR (Westergren method) and CRP (immunonephelometric method) were analyzed at admission and then every 12 hr for 48 hr after admission. Severity of AP was defined according to the Atlanta definition. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of ESR, CRP and combination of ESR/CRP in predicting severe AP were calculated. Results: Fifty patients with AP (16 severe, 34 mild) were enrolled. The aetiologies of AP were alcohol 32%, biliary 34%, post-ERCP 20%, miscellaneous 8% and idiopathic 6%. ESR was significantly higher in patients with severe AP compared to mild AP. The optimal cutoff level of ESR was 60 mm/hr. At 36 hr after admission, the sensitivity, specificity, PPV and NPV of ESR (>60 mm/hr) to predict severe AP were 73%, 59%, 48%, and 81%, respectively, compared to 87%, 87%, 76% and 93%, respectively by CRP (>150 mg/L). At 48 hr after admission, the results of ESR (> 60 mm/hr) were 81%, 60%, 52% and 86%, respectively, compared to 81%, 83%, 72% and 89%, respectively of CRP (>150 mg/L). The combination of either elevated ESR or CRP increased the sensitivity and NPV to predict severe AP to 100% and combination of elevated ESR and CRP increased the specificity and PPV to 97% and 90%, respectively in predicting severe AP at 36 hr after admission. Conclusion: ESR >60 mm/hr is useful for predicting severe AP. Although slightly inferior to CRP, ESR is simpler and more widely-available. The combination of ESR and CRP improved both sensitivity and specificity in predicting severe AP over CRP or ESR alone.
T1302 Moderately Severe Acute Pancreatitis: A Prospective Validation Study of This New Subgroup of Acute Pancreatitis Rupjyoti Talukdar, Santhi Swaroop Vege, Suresh T. Chari, Magdalen A. Clemens, Randall K. Pearson
T1300 Serum Neutrophil-Associated Gelatinase Lipocalcin (NGAL) Levels As An Early Biomarker of Severe Acute Pancreatitis Venkata Muddana, Georgios I. Papachristou, Subhankar Chakraborty, Sukhwinder Kaur, Neil Sharma, David C. Whitcomb, Randall Brand, Surinder K. Batra
Background and Aims: We have earlier described the entity of moderately severe acute pancreatitis (MSAP) (Am J Gastroenterol (In press)), characterized by presence local complications (i.e., pancreatic necrosis and/or fluid collections).without organ failure. MSAP patients meet criteria for severe acute pancreatitis (SAP) as defined by Atlanta criteria; however, their mortality is low and similar to that seen in mild acute pancreatitis (MAP) but they have prolonged hospital stay characteristic of SAP. Our aim was to validate the existence of the entity of MSAP in a prospectively identified cohort of patients with AP. Methods: We classified a prospective cohort of 82 AP patients directly admitted to Mayo Clinic Hospitals between 6/2004 and 8/2007 into 3 subgroups: (a) SAP: presence of organ failure with/ without local complications, (b) MSAP: presence of local complications without organ failure and (c) MAP: defined by no organ failure or local complications. The outcome variables studied were need for ICU care, ICU days, total hospital days, need for interventions and death. We compared continuous variables using t-test and nominal variables using Chi square test. Results: Patients in the 3 subgroups did not differ in age, gender, hematocrit at admission or body mass index. Patients with MSAP did not require ICU care and had no mortality despite presence of necrosis and hospital stay similar to those who had organ
Introduction: Acute pancreatitis (AP) is a common inflammatory disorder with 10-20% progressing to severe disease. Up to now there is no early biomarker identified to predict accurately the course of AP. Neutrophil associated gelatinase lipocalin (NGAL) is a glycoprotein released from neutrophils and other epithelial cells and is upregulated in cells under “stress”, e.g. from infection, inflammation, or neoplastic transformation. Based on a previous finding of significantly elevated NGAL levels in humans with AP compared to normal controls, the aim of this study was to determine whether NGAL serum levels predict severity in the early course of AP. Methods: NGAL serum levels were measured using an ELISA assay in a frozen serum samples from patients with AP collected on day 1-7 from the onset of pain. Severe AP was defined as the presence of failure in at least one organ (cardiovascular, renal or pulmonary) for > 48 hours. Comparisons were made using Mann-Whitney test. Receiver Operating Characteristics (ROC) curves, sensitivities and specificities were calculated. Results: NGAL levels were measured from a total of 44 patients with AP. 28 patients (64%) had mild AP and 16(36%) had severe AP. NGAL serum levels were significantly
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pseudocysts. On univariate analysis factors associated with pseudocyst formation following AP were male sex (OR-3.17; 95% CI 1.06-9.49), palpable mass (OR- 8.29; 95% CI 2.1135.18), blood sugar > 150mg% (OR- 4.68; 95% CI 1.57-13.95), a high CRP (AUROC 0.867:SE 0.093; 95% CI 0.684-1.050), necrosis (OR-7.01; 95% CI 2.31-21.28), AFC (OR9.34; 95% CI 3.02-28.90), ascites (OR-22.15; 95% CI 4.49-109.38), pleural effusion (OR5.44; 95% CI 1.67-17.73), higher grade of pancreatitis (Grade E/C OR-15.75; 95% CI 1.65150.14) and higher CTSI score (AUROC-0.813: SE 0.05; 95% CI 0.71-0.92). On multivariate analysis, male sex (p=0.024), a palpable mass (p=0.028), ascites (p=0.005) and a high CTSI score (p=0.013) were associated with formation of pseudocyst. Conclusion: This study shows that male sex, palpable mass, ascites and high CTSI score at admission can predict the development of pseudocyst following an attack of acute pancreatitis.
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failure (Table). The following parameters were found to be significantly less in the MAP group when compared to SAP: need for ICU care, total hospital days, local complications, organ failure, interventions and death. Conclusions: MSAP has been validated in this prospective cohort as an exclusive entity, different from SAP and MAP. Table: Comparison between patients with MAP and MSAP
T1305 Is Oral Re-Feeding While On Parenteral Narcotics Beneficial in Mild Acute Pancreatitis? Kathryn A. Repas, Brian C. Jacobson, Rachael S. Diamond, Darwin Conwell, Bechien Wu, Peter A. Banks Introduction: Optimal timing to initiate re-feeding following mild acute pancreatitis remains controversial. We have reported in a prospective, randomized, controlled trial that initiation of a low fat solid diet following mild acute pancreatitis appears to be safe, provides more calories than a clear liquid diet, and does not increase length of hospitalization [Clin. Gastro. Hepatol. 2007]. We excluded patients who were still receiving parenteral narcotics at the time of re-feeding. Aims: To determine the impact of parenteral narcotics on success of refeeding in patients with mild acute pancreatitis. Methods: This was a retrospective review of patients with mild acute pancreatitis who qualified for the prospective oral re-feeding study but were excluded specifically because they received parenteral narcotics at the time of re-feeding (i.e. within 6 hours of re-feeding). Comparisons were made between patients who were excluded (Group A) and patients who participated in the oral re-feeding study (Group B). Failure of re-feeding was defined as need to be made NPO and increased narcotic requirement after re-feeding. Statistical Analysis: Graphpad Prism 5.01 Software. Results: 45 patients received narcotics within 6 hours prior to being re-fed (Group A). There were no statistical differences in age or gender between this group and the 121 patients who participated in the re-feeding study (Group B). The mean pain score at the time of re-feeding was higher in Group A than Group B (3.75 vs. 1.1, t-test p<0.0001). Patients in Group A were more likely to be made NPO after re-feeding (19/45 (42%) vs. 13/121 (11%), Fisher exact test p<0.0001). In addition, patients in Group A were more likely to require narcotics after re-feeding (37/45 (82%) vs. 15/121 (12%), Fisher exact test p<0.0001). Group A was re-fed sooner than Group B (2.1 vs. 2.5 days, t-test p=0.0054). However, earlier re-feeding of Group A resulted in a prolongation of the length of stay after re-feeding(3.1 vs. 1.8 days, t-test p=0.0016). Total length of hospital stay between Group A and Group B showed no difference (5.9 vs 4.3 days, t-test p=0.3014). Conclusions: 1. Patients still receiving parenteral narcotics prior to re-feeding were more likely to fail re-feeding. 2. Re-feeding while still receiving parenteral narcotics did not decrease hospital stay. 3. Re-feeding while on parenteral narcotics may not be beneficial.
* Significant difference (p value <0.05) when compared vs SAP ** Significant difference (p value <0.05) when compared vs MSAP T1303 Acute Pancreatitis Requiring ICU Admission Associated with An Earlier and Milder Form of Metabolic Acidosis Mark Saxena, Daniel Blachman, Anthony J. Nici, Adnan Muhammad, Girish Prajapati, Capecomorin Pitchumoni Introduction: Ranson's criteria states that a serum bicarbonate (base) decrease of 4 meq/L 48 hours after admission contributes to diminished survival. A more recent study suggests that earlier metabolic acidosis at 0-24 hours after admission is associated with adverse outcomes. The retrospective analysis of 74 patients using “multiple logistic regression analysis showed that [among the 27 risk factors] only acidosis (pH<7.35) was associated with death” at 24 hours (1). Our study examines the role of early metabolic acidosis, defined by routinely measured bicarbonate level, in the need for ICU admission in acute pancreatitis. Methods: Subject data was retrospectively collected from five hospitals over two years. Included subjects had: A physician-determined diagnosis of acute pancreatitis, abdominal pain, and amylase and lipase levels three times above normal. Outcomes measures included: ICU admission, bacteremia, length of stay, and pancreatitis-related complications (e.g. psuedocyst). Subjects were excluded for one of five severe, chronic medical conditions (e.g. ESRD on dialysis). Metabolic acidosis was defined as a serum bicarbonate level less than 22 meq/ L. This represented a base deficit of 2 meq/L. Associations between prognostic and outcome measures were assessed using Fisher's chi square test, potentially logistic after adjusting for: age, sex, race, smoking and alcohol. Results: Among the 174 charts reviewed, 119 subjects met inclusion/exclusion criteria and had sufficient data for comparison analysis. Subjects in all groups were similar with regards to age and sex. Fisher's chi square analysis showed that serum bicarbonate <22 meq/L on admission was more closely associated with the need for ICU admission (OR = 4.61 95% CI 1.39, 15.30 P=0.017) than admission bicarbonate >22 meq/L. No significant associations were found between metabolic acidosis and bacteremia, complications, or length of stay. No deaths were reported among included subjects. Conclusions: A milder, earlier form of metabolic acidosis than described in Ranson's 48-hour criteria was associated with ICU admission. This may be an early marker for intensive care level supervision in acute pancreatitis. References: 1. Zhu AJ, Shi JS, Sun XJ. Risk factors influencing mortality of patients with severe acute pancreatitis within 24 hours after admission. Hepatobiliary Pancreat Dis Int. 2003;2:453-7. 2. Swaroop VS, Chari ST, Clain JE. Severe acute pancreatitis. JAMA. 2004; 291: 2865-8. 3. De Campos T, Braga CF, Kuryura L, Hebara D, Assef JC, Rasslan S. Changes in the management of patients with severe acute pancreatitis. Arq Gastroenterol. 2008; 45:181-5.
T1306 Multiplex Serum Marker Panel Accurately Predicts Systemic Complications of Acute Pancreatitis Georgios I. Papachristou, Venkata Muddana, Christopher J. Langmead, Gilles Clermont, David C. Whitcomb Background: The clinical course of acute pancreatitis (AP) remains difficult to predict prior to the development of organ dysfunction, because of the complex dynamics of interacting systems from the molecular to organ levels and the variability between human subjects. We hypothesize that a limited number of pathways link the initiation of the acute inflammatory response to organ dysfunction, and identification of optimal biomarkers of pathway activation will improve prediction of clinical endpoints and provide readout of treatment effectiveness. Aim: To combine statistical modeling with machine-learning approaches and test the above hypothesis using clinical information and biomarkers from the Severity of Acute Pancreatitis Study (SAPS-1). Methods: 21 commonly measured clinical variables were recorded and 26 serum biomarkers were measured. Severe AP was defined as 48 hours of persistent organ dysfunction. Machine learning algorithms ranked biomarkers by information gain with respect to the outcome and provided corresponding prediction accuracies and areas-under the receiver-operating curve (AUC). Predictions were validated by 10-fold cross-validation. Results: 185 patients were prospectively ascertained (mean age 53 years; 53% males), 39 of which were classified as severe AP (21%). Only three of the 21 common clinical variables yielded a cross-validated information gain >0.2: admission hematocrit (0.55), glucose (0.25) and AST (0.22). By using Naïve Bayes, their accuracy in predicting organ failure was 82% with AUC of 0.86. 93 serum samples collected from 59 subjects (severe, mild) on days 2 (n=5, 20), 3 (n=7, 20), 4 (n=8, 14) and 7 (n=8, 11) were analyzed for biomarkers. Optimal performance was achieved with a 5 biomarker panel including angiopoietin-2 (Ang-2), resistin, soluble TNF receptor-1 (TNF-R1), hepatocyte growth factor (HGF) and interleukin 8 (IL-8). Accuracy of the panel in predicting organ failure reached 96% on day 2 and 3 after onset of pain with AUC of 0.81 and 0.99, respectively. Conclusions: New methods of pattern analysis of early markers of AP improve the predictive accuracy of biomarker panels and may be useful in classifying patients into high- and low-risk groups.
T1304 Pseudocyst Formation in Acute Pancreatitis (AP): Prediction At Admission By Clinical, Biochemical and Radiological Parameters K. S. Poornachandra, Deepak K. Bhasin, Birinder Nagi, Saroj K. Sinha, Surinder S. Rana, Nusrat Shafiq, Rajesh Gupta, Mandeep Kang, Samir Malhotra, Kartar Singh Objective: To study clinical, biochemical & radiological parameters at admission that predict development of pseudocyst following AP. Methods: 75 consecutive patients with AP were prospectively enrolled & subjected to clinical & laboratory examination. Contrast enhanced computerized tomography (CECT) of abdomen done after day 3 of pain. Severity staged according to Balthazar Ranson grading and CT severity index (CTSI). Abdominal ultrasound repeated at 2nd and 4th week. At 4 weeks CECT repeated in symptomatic patients and if abdominal ultrasound showed a pseudocyst. Results: 10 patients were excluded and 65 patients (44 males) were finally studied. The median age was 37 (40.9 ± 15.5) years. Etiology of AP was alcohol in 24, gall stones in 18, both in 4, drugs in 4, pancreas divisum in 2, post ERCP in 1, trauma in 1 and idiopathic in 11 patients. At admission, palpable mass, blood sugar > 150 mg%, ascites and pleural effusion was present in 3 (4.6%), 41 (63.1%), 45 (69.23%), and 45 (69.23%) patients respectively. Acute fluid collections (AFC) were seen in 34 (52.31%) patients. Necrosis was noted in 38(58.46%) patients (<30% necrosis, 30-50% necrosis and >50% necrosis in 36.8%, 26.3% and 36.8% patients respectively). Grade A, B, C, D & E pancreatitis was present in 1.5%, 3.1%, 43.1%, 23.1% and 29.2% patients respectively. The mean CTSI score was 5.09±2.94. On follow up, 34 (52.3%) patients developed pseudocyst and majority (52.94%) had multiple pseudocysts. Of the 34 AFC noted on the initial imaging, 4 resolved by 2nd week and 12 new were noted in the 2nd week and of these, 8 resolved. Of 19 patients with grade E pancreatitis, 18 developed
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