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. 21 patients required surgery , out of which 12 had preoperative pigtail drainage. Mean follow up was 26.2 months. 18 patients (51.4%) had readmissions . 14 patients (40%) had exocrine deficiency and 17 patients (48.5%) had endocrine deficiency .In comparison to sterile necrosis, patients with infected necrosis had higher incidence of exocrine insufficiency( 0 vs 20%, p-0.017) and endocrine insufficiency(14.2% vs 56.5%, p-0.052). Patients managed non-operatively had less incidence of exocrine insufficiency(14.2% vs 57.1%, p-0.013) and endocrine sufficiency(28.5% vs 61.9%, p-0.055) in comparison to those who underwent necrosectomy. 31 patients (88%) had morphological changes in MPD . Patients with incomplete or absent MPD had significantly higher incidence of exocrine deficiency than those with completely visualized duct(60% vs 0%, p-0.013). Higher incidence of complete nonvisualisation of MPD was found in operated patients than the conservative group( 28.6% vs 0%, p-0.028). Other morphological changes in pancreas were also higher in operated group but was not statistically significant. CONCLUSION: Patients of severe acute pancreatitis on follow up had significant functional, and morphological changes with 50% patients requiring readmission. Patients who were managed conservatively had lesser incidence of exocrine and endocrine deficiencies, though there was no significant difference in pancreatic morphological changes. Tu1508 Diagnostic Accuracy of Endoscopic Ultrasound and Cyst Fluid Analysis in Histologically Confirmed Pancreatic Cysts Disha Mahendra, Srinivas Gaddam, Dayna S. Early, Daniel Mullady, Riad R. Azar, Faris Murad, Sreenivasa S. Jonnalagadda, Steven A. Edmundowicz, Sachin Wani Background: Distinction between mucinous and non-mucinous cysts is clinically significant due to the malignant potential of mucinous cysts. Diagnostic criteria based on EUS morphology, cyst fluid cytology and cyst fluid analyses [carcinoembryonic antigen (CEA)] have been proposed to differentiate between these entities. However, validation of these criteria is limited with a wide range of cutoff values for CEA reported. Aims: - To evaluate the diagnostic accuracy of EUS morphology and cyst fluid analysis in differentiating between mucinous and non-mucinous pancreatic cysts using histology or malignant cytology as gold standard. - To evaluate and validate performance characteristics of CEA and amylase levels. Methods: From a database of consecutive pts undergoing EUS for evaluation of pancreatic cysts, patients with histologic confirmation of cyst type (surgical or cancer on cytology from EUS FNA - gold standard) who underwent EUS-FNA were identified. Demographics and EUS morphology (size, location, communication with pancreatic duct (PD), presence of mural nodule or solid mass, unilocular/multilocular, macrocystic morphology, honey combing (microcystic morphology), and EUS impression of a pseudocyst) were noted. FNA results, including cyst fluid CEA and amylase level, and cytology features of mucin, cellular atypia or cancer were recorded. Records were reviewed to determine if surgical resection was performed. Univariate analysis was performed followed by multivariate logistic regression analysis to identify predictors was performed. ROC curves were generated for cyst fluid CEA and amylase levels. Results: 149 pts met inclusion criteria and all underwent EUSFNA; mean age 63.9 yrs (SD 11.3), 87% Caucasians and 56% females. 100 pts underwent surgery - Whipple's surgery in 48, distal pancreatectomy in 49 and others in 3. Cancer on cytology was noted in 70 (50.7%) pts.There were 128 pts with mucinous cysts (including IPMN) based surgical histology or cytology and 21 non-mucinous cysts (serous 8, pseudocyst 5, neuroendocrine others 6, others 2). Comparison of demographics, EUS morphology features and FNA results between mucinous and non-mucinous cysts have been highlighted in Table. No significant predictors on EUS and FNA results were identified on multivariate logistic regression analysis. Area under ROC curve was 0.66 for CEA (cut off of 83 ng/ml - sensitivity, 64.4% and specificity, 61%) and 0.59 for amylase (cut off of 200 IU/L sensitivity, 61% and specificity, 50%) (Figure). Conclusions: Results from this study highlight the lack of predictors (EUS morphology and cyst fluid analysis)in reliably differentiating mucinous and non-mucinous pancreatic cysts. These results add to the growing body of literature on wide variation in CEA levels in pancreatic cysts. Identification of other cyst fluid markers should be studied in future trials. Univariate analysis
Tu1509 The Diagnostic and Prognostic Significance of Serum IgG4 Elevation in Pancreatic Cancer Ryan Law, Taiwo Ngwa, Phil Hart, Suresh T. Chari Introduction: Serum IgG4 (sIgG4) levels are frequently elevated in autoimmune pancreatitis (AIP); however, recent studies have shown that sIgG4 levels are also elevated in 7-10% of patients with pancreatic cancer (PaC)1,2. It is unclear if there are demographic or serologic characteristics that distinguish elevated sIgG4 in AIP from that in PaC. It is also unknown if sIgG4 elevation has prognostic significance in PaC. Methods: Patients who had sIgG4 measured and had either histologically confirmed PaC (n=435) or type 1 AIP meeting HISORt criteria (n=90) were identified from Mayo Clinic's Pancreas Cancer SPORE and AIP databases, respectively. Subsets of patients with elevated sIgG4 in PaC (n=40) and AIP (n=60) were compared to see if there were features that distinguished the two diseases. PaC patients with elevated sIgG4 were compared with PaC cases without sIgG4 elevation (n=395), in regards to demographics, resectability, and mortality. Results: Compared to PaC, AIP subjects were more likely to have any elevation in sIgG4 (67% vs 9%, p<0.001) and sIgG4 >2X upper limit of normal (ULN) (42% vs 2%, p<0.001). Among those subjects with elevated sIgG4, AIP and PaC were similar with regard to age at diagnosis (64.0 years +/-13.6 vs 65.9+/12.3, p=0.45) and gender (85% male vs 78%, p=0.13). In patients with elevated sIgG4, the level was 1-2X ULN in 80% of PaC and 37% of AIP (p<0.001) subjects. Among patients with sIgG4 1-2X ULN, AIP and PaC subjects have similar IgG4/IgG ratios (14.0% vs 15.5%, p=0.10) and an insignificant difference in rates of total IgG level elevation (9% vs 23%, p= 0.17). PaC patients with elevated IgG4 had similar rates of resectability compared to PaC patients with normal sIgG4 (21% vs 31%, p=0.68), and the mortality was similar in the two groups (85% vs 91%, p=0.25) as well. Conclusions: Mild elevation of sIgG4 is unable to distinguish AIP from pancreatic cancer. In patients with PaC, IgG4 elevation has no prognostic significance with respect to tumor resectability and survival following diagnosis. References: 1. Raina A, Krasinskas AM, Greer JB, et al. Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis. Arch Pathol Lab Med 2008; 132:48-53. 2. Ghazale A, Chari ST, Smyrk TC, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol 2007; 102:1646-1653. Tu1510 Validation of the International Consensus Guidelines for Branch Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Meta-Analysis Neeraj Anand, Kartik Sampath, Anne Fraser, Bechien U. Wu Background: International consensus guidelines for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of main duct IPMNS and branch duct IPMNs with certain characteristics. Features that are considered concerning for malignancy are cyst size >30 mm, mural nodules, dilated main pancreatic duct, and symptoms. We performed a quantitative meta- analysis to evaluate risk of malignancy associated with each of these proposed features of IPMNs. Methods: We performed a comprehensive literature search using MEDLINE from January 1, 1996 (publication WHO classification) to November 11, 2011. Studies were selected for analysis if they included any of the features mentioned in the consensus guidelines for surgical resection of main duct and branch duct IPMNs. Case reports, editorials and review articles were excluded. Studies were also excluded if they did not provide histological data for IPMNs. Data were extracted for the following :(1) cyst size > 3 cm, (2) the presence of mural nodules, (3) dilated main pancreatic duct, (4) symptoms and (5) main duct vs. branch duct IPMNs. Malignant IPMN was defined as carcinoma in situ or more advanced histology. Separate meta-analysis was performed for each risk factor to calculate the pooled odds ratio (OR) using a random effects model. Heterogeneity was assessed using the I2 test. Results: Initial
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search yielded 1,047 studies of which 526 abstracts were reviewed based on relevance. Of these 188 articles were fully reviewed and 41 met the pre-specified inclusion criteria. Overall there were 5788 patients and 3304 branch duct IPMNS included in the final analysis. There were 16 studies including 1058 patients in the analysis of cyst size. Cyst size greater than 3 cm substantially increased the risk of malignancy OR 62.4 [95% CL 30.8, 126.3]. Analysis of 19 studies and 1452 patients indicated that the presence of a mural nodule within the cyst was also a strong risk factor for malignancy OR 9.3 [5.3, 16.1]. 8 studies incorporating data from 358 patients were included in the analysis of main pancreatic duct dilation OR 7.27 [3.0, 17.4]. In addition, main duct IPMNs carried a higher risk of malignancy then branch duct IPMNs (OR 4.7 [3.3, 6.9]). There was a weak association between patient symptoms and malignancy OR 1.6 [1.0, 2.6]. There was moderate heterogeneity among studies (I2 range 34- 67). Conclusions: In this meta-analysis we confirmed that cyst features proposed by the international Sendai consensus guidelines for resection of IPMN were highly associated with malignancy. Despite inherent selection bias towards patients that underwent surgical resection, findings from this meta-analysis of the published literature indicate that not all cyst features should be weighted equally. Cyst size was most strongly associated with malignant IPMN.
Tu1512 The Effect of Gastric Acid Suppression With Proton Pump Inhibitors (PPI) on the PEAK Bicarbonate Concentration of a Secretin Stimulated Endoscopic Pancreas Function Test Luis F. Lara, Marlon F. Levy, Morihito Takita, Shinichi Matsumoto, J. S. Burdick, Bhavani Moparty, Robert D. Anderson, Daniel C. DeMarco Background/Aims Inactivation of lipase and trypsin due to gastric acid and pepsin was recognized years ago as a mechanism of failure for pancreas enzyme supplements which could be reversed to a point by acid suppression therapy. Previous pancreas function tests (PFT) after CCK or secretin stimulation required gastric content aspiration in part to avoid acid contamination and pancreas enzyme inactivation. Endoscopic PFT (ePFT) after secretin stimulation have shown similar yields to the previous PFT, but the stomach is aspirated only once before duodenal aspirations are performed which could affect the test and the effect of acid suppression on test performance is unknown. Methods ePFT was performed after synthetic secretin administration (ChiRhoClin, Inc., Burtonsville, MD). After gastric fluid aspiration the endoscope was advanced to the duodenum and 4 duodenal aspirations were done 35 minutes after secretin at 5 minute intervals. An autoanalyzer (Corning 965, USA) calibrated to a bicarbonate of 80 meq/L was used, and peak bicarbonate concentration (PBC) of >80 mEq/L was considered normal. Patients who have an ePFT are registered in a IRB approved unidentifiable database. Patients are allowed to take medication before endoscopy unless indicated, and those who reported being on a PPI were extracted and used for the study. Results 61 ePFT have been performed. Chronic pancreatitis (CP) was established in 19 patients, thus 42 patients did not have CP. The median PBC was 74 (41.894) in patients with CP compared to 104 (18.9-135) in patients without CP (p<0.001). 7 of 19 pts with CP (37%) and 23 of 42 pts without CP (55%) were on a PPI, respectively. Results are summarized in the table. The median PBC was higher in patients with CP taking a PPI (80.6 mEq/L) compared to CP not on a PPI (66.7 mEq/L) and this difference was borderline significant (p=0.05). The PBC was similar in patients without CP on or off a PPI, and remained statistically different compared to patients with CP whether they were on a PPI or not (p<0.003). Conclusions The effect of acid suppression on ePFT is not known. In this retrospective study the PBC was higher when patients with CP were on a PPI, but the PBC remained statistically different compared to patients without CP on or off a PPI suggesting that ePFT was able to differentiate between the groups. Also, PPI use did not affect the PBC in patients without CP. While it is impossible to confirm if a PPI was taken the day of the procedure we typically do not stop this medication for an endoscopy. This result suggests an effect of PPI on the pancreatic bicarbonate concentration, especially in patients with suspected CP on a PPI. Prospective studies are necessary to determine possible effects of PPI when interpreting ePFT results. Comparison of Peak Bicarbonate Concentration in Patients With or Without Chronic Pancreatitis On or Off a Proton Pump Inhibitor
Tu1511 Pancreatitis Prior to Pancreatic Cancer: Clinical Features and Influence on Outcome Ivana Dzeletovic, M. Edwyn Harrison, G. Anton Decker, Rahul Pannala, Cuong C. Nguyen, Qing Wu, Douglas O. Faigel Objective: Patients with pancreatitis may be present with or be at risk for pancreatic adenocarcinoma (PA). The association between chronic pancreatitis and PA is well established. In addition, acute pancreatitis has been recognized as a rare presentation of PA. The clinical features and outcome of PA patients with a prior history of pancreatitis have not been evaluated. Aims: Evaluate a large tumor registry to determine whether a prior history of pancreatitis influenced the survival of patients with PA. Methods: A database analysis of PA patients from 1992 to present in the Mayo Clinic Pancreas SPORE (Specialized Program of Research Excellence) was performed. The clinical features and outcome of PA patients with pancreatitis (acute, chronic, hereditary or unknown) at or before their cancer diagnosis were compared to PA patients without prior pancreatitis. Differences of continuous variables between the two groups were assessed by Kruskal-Wallis test and difference of category variables between the two groups were assessed using Chi-square test. Log rank test was used to assess survival difference between the two groups. P value < 0.05 was considered to be significant. Results: A cohort of 2357 patients with the diagnosis of PA was analyzed. A total of 197 patients with diagnosis of pancreatitis at or prior to the diagnosis of PA were identified. (Table 1) Patients with PA and pancreatitis at or prior to the diagnosis of PA had significantly better survival (median, days 325 vs. 387, p=0.0036) as presented in the KaplanMeier curve in Figure 1. Conclusion: Patients with pancreatitis at or prior to diagnosis with PA had more weight loss and diabetes but were diagnosed with PA at a significantly earlier stage, were significantly more likely to have pancreatic surgery, and had significantly better survival. Further study is needed to evaluate if screening for pancreatic malignancy in patients with a history of pancreatitis would provide survival benefit and be cost effective.
* p=0.05;p<0.003 CP=chronic pancreatitis PPI=proton pump inhibitor Tu1513 Comparison of Mutational Profiling of Cyst Fluids to Surgical Outcomes Sydney D. Finkelstein, Eric Ellsworth, Jamie Bleicher, Valerie Stearns, W. Christine Spence Introduction: The diagnosis and treatment of pancreatic cystic disease can be difficult based on chemistry and cytology analysis of the aspirated fluid due as these modalities may not fully represent the degree of neoplastic transformation. An understanding of genomic alterations can address both issues providing clinically actionable information. We developed molecular testing that utilizes small amounts of pancreatic cyst fluid and integrates with first line imaging, chemistry and cytology findings. We report our experience with a cohort
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