1
AGA Abstracts reported abdominal complaints as opposed to 7.6% of those without PC(s) (p = 0.589). None of the individuals with PC(s) had pancreatic disease in their medical history. Conclusion: In individuals undergoing preventive medical examination with MRI, the prevalence of PCs was 2.2%. Of these PCs, 5.3% were 30 mm, 8% were multilocular and in 10% of cases may represent side-branch IPMN. Cyst presence correlated with increasing age, no difference of prevalence by sex was found. Abdominal complaints did not correlate with PC presence. 967 Main-Duct and Combined IPMNs Are the Same Clinical Entity and Distinct from Branch-Duct IPMNs Stefano Crippa, Carlos Fernandez del-Castillo, Roberto Salvia, Dianne M. Finkelstein, Claudio Bassi, Ismael Dominguez, Paola Capelli, Mari Mino-Kenudson, Gregory Y. Lauwers, Massimo Falconi, Sarah P. Thayer, Stefano Partelli, Paolo Pederzoli, Andrew L. Warshaw Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas comprise main-duct (MD), branch-duct (BD) and combined types. There is still no consensus whether MD- and BD-IPMNs are different points on a spectrum or altogether different diseases, and where combined IPMNs fit. The aim of this study was to evaluate the clinico- epidemiological characteristics and prognosis of a large series of patients with IPMNs, to elucidate differences among the three types. Methods: 389 patients who underwent pancreatic resection for a histologically confirmed IPMN were identified. Surgical specimens were re- reviewed and eventually re-classified. The clinico-pathologic characteristics of the three subtypes were contrasted. Results: 159 (41%) patients had BD- IPMNs, 149 (38%) combined IPMNs, and 81 (21%) MD-IPMNs. MD- and combined IPMNs occurred more frequently in males (56%) while BD-IPMNs were seen more often in females (57%) (p<0.05). All IPMNs subtypes were generally located in the proximal pancreas with no age differences among different IPMNs. Incidental diagnosis was more common in BD-IPMNs (34.5%) than in MD- (13.5%) and combined (19%) ones (p=0.001), while jaundice and weight loss were significantly more frequent in MD- and combined-IPMNs (p<0.01). Adenoma was the most common histological type in BD-IPMNs (44%) and its prevalence in MD- and combined IPMNs was significantly lower (11% and 8%, p=0.0001). Conversely the rate of invasive cancer was 11% in BD-IPMNs and 42% and 48% in combined- and MD-IPMNs (p=0.0001). Patients with combined and MD-IPMNs with invasive cancer were older than those with noninvasive tumors -suggesting tumor progression- while this age difference was not found in BD-IPMNs. 5-year disease specific survival was 100% for patients with noninvasive BD- IPMNs and combined-IPMNs and 95% for patients with noninvasive MD-IPMNs (one patient who underwent total pancreatectomy for in-situ-carcinoma had peritoneal recurrence); 5- year disease specific survival was 56%, 51%, and 64%, for BD-IPMNs, MD-IPMNs, and combined-IPMNs with invasive cancer, respectively. Conclusion: BD-IPMNs have a specific profile, likely representing an entity distinct from other IPMNs, and combined IPMNs show close overlapping similarities with MD-IPMNs in regard to clinico-pathological and epidemiological characteristics. Combined IPMNs should be considered an extension of MD- IPMNs to the branch-ducts, and these two subtypes show a more aggressive biological behavior compared to BD-IPMNs 968 Performance Characteristics of Cyst Fluid CEA Analysis for the Diagnosis of Mucinous Cysts of the Pancreas Satish Nagula, Timothy J. Kennedy, Mark A. Schattner, Murray F. Brennan, Hans Gerdes, Arnold J. Markowitz, Laura H. Tang, Peter J. Allen Background: Elevated cyst fluid CEA levels (>200 ng/ml) have been demonstrated to be highly diagnostic of mucinous cysts of the pancreas (intraductal papillary mucinous neoplasm - IPMN, and mucinous cystic neoplasm - MCN). Methods: A prospectively maintained pancreatic cyst registry was reviewed and 191 patients with cystic neoplasms of the pancreas were identified who had undergone endoscopic ultrasound and fine needle aspiration between 2001 and 2008. All patients had cyst fluid CEA measured. Patient demographics, imaging studies, cyst characteristics, pathology, and treatment variables were recorded. Performance characteristics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) of elevated fluid CEA (>200 ng/ml) for detecting a mucinous cyst and detecting malignancy (in situ or invasive adenocarcinoma) were calculated in those who had a patholo- gically proven diagnoses. The outcome of patients with an elevated cyst fluid CEA who did not undergo resection was documented. Results: A pathologically proven diagnosis was obtained in 63 patients (33%). Mucinous neoplasms were identified in 40/63 (64%): MCN, n=9; benign IPMN, n=27; malignant IPMN, n=4. Median cyst size was 3.3 cm for non- mucinous cysts (median CEA: 117 ng/ml) and 3.0 cm for mucinous cysts (median: CEA 1272 ng/ml). A cyst fluid CEA > 200 had a sensitivity, specificity, PPV, and NPV of 85%, 61%, 79%, 70%, respectively, for identifying a mucinous neoplasm. The extent to which CEA was elevated was not associated with the presence of malignancy (mean fluid CEA: mucinous malignant 7025 ng/ml, mucinous non-malignant 4271 ng/ml; p=0.52). An addi- tional 128 patients were observed (mean follow-up 24 months, range 0-120 months); 23 of these patients had a cyst fluid CEA > 200 ng/ml and were followed for more than 12 months. None of these patients developed radiographic changes that resulted in surgical resection. Cyst fluid CEA was not associated with cyst growth, even amongst the subset of patients with elevated cyst fluid CEA and extended followup. Conclusions: In this study, cyst fluid CEA > 200 ng/ml was found to have a PPV of 79% and NPV of 70% for identifying mucinous neoplasms. In contrast to prior published reports, this registry contains a large number of IPMNs, and demonstrates that CEA has similar efficacy for the diagnosis of both MCN and IPMN. Elevation of cyst fluid CEA was not associated with malignancy, or a higher likelihood of cyst growth. Better markers for identifying dysplasia in mucinous cysts and predicting cyst behavior are needed to aid in management. A-148 AGA Abstracts 969 Proteomic Analysis of Cyst Fluid Mucin Expression Is Significantly More Accurate Than Conventional Cyst Fluid Analyses in the Clinical Assessment of Pancreatic Cystic Lesions Karolina Sjöberg, Malin E. Johansson, Anders G. Hyltander, Evangelos Kalaitzakis, Morteza Shafazand, Jan Hansen, Henrik Sjovall, Gunnar C. Hansson, Riadh Sadik The assessment of pancreatic cystic lesions (PCL) - the detection and staging of cystic/cyst- like tumors (CT) - is a clinical challenge. Mucin expression has been observed in mucinous and serous CTs and in ductal adenocarcinomas (that may appear cyst-like), but not in pseudocysts. Ductal adenocarcinomas exhibit MUC1 overexpression, which, when seen in mucinous CTs, supposedly indicates invasive disease. However, prospective studies are lacking, as are studies that use proteomics and thus avoid the diagnostic pitfall of differential mucin glycosylation. AIMS: To explore the utility of proteomic analysis of cyst fluid mucin expression, in the clinical assessment of PCLs. METHODS: Patients referred for endoscopic ultrasound with fine needle aspiration of a PCL were prospectively included. Cytology with PAS diastase mucus stain, and cyst fluid CEA quantification were performed. Cyst fluid samples (~20μl) were then run on a gel electrophoresis; high mass bands were cut out, trypsinized and analyzed by nanoLC-mass spectrometry and MS/MS on an FT mass spectro- meter. For peptide identification the Mascot software and an in-house mucin database were used. Primary diagnostic endpoints: 1)Surgical pathology (n=8); 2)Follow-up including imaging (n=12); 3)Preliminary diagnosis, based on all clinical data except proteomics results (blinded) (n=9). RESULTS: 13 females and 16 males were included, age range 36-86, median 64. According to our primary diagnostic endpoints there were 19 CTs and 10 pseudocysts. We compared the sensitivity, specificity and accuracy for detection of CTs, for proteomic mucin expression analysis and cytology (Table 1). In line with earlier reports, 2/3 serous CTs expressed MUC6 alone, a pattern not seen for other PCLs. The diagnostic utility of CEA was flawed by a lack of results for 10/29 PCLs due to low cyst fluid yield. For the cases with a surgical pathology, we compared the capacity for preoperative detection of malignancy, for proteomics (presence/absence of MUC1 expression) and cytology. Sensitivity was 57% for proteomics and 13% for cytology; specificity 100% for both. CONCLUSION: Proteomic mucin expression analysis was significantly more accurate than standard cyst fluid analyses in the clinical assessment of PCLs. MUC1 expression was more sensitive than cytology as a marker for malignancy. Minute amounts of cyst fluid are required for proteomics, whereas cyst fluid yield may restrict the diagnostic utility of CEA. Table 1 Cyst fluid CEA (cut-off 400ng/ml): Sensitivity:50% Specificity:89% 970 A 13-Nation Population Survey of Upper Gastrointestinal Symptoms: Age and Gender Sebastian Haag, Jane M. Andrews, Judith D. Gapasin, Andreas Keller, Gerald Holtmann Background: There is a lack of studies which assess and compare the prevalence of upper gastrointestinal (GI) symptoms contemporaneously in various countries using a uniform, standardised method. Previous data collected in separate studies using various different survey instruments have suggested some variability in the prevalence of symptoms between nations. Thus the aim of this study was to determine the prevalence of upper GI symptoms in 13 European countries (Austria, Belgium, Denmark, Finland, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Spain, and Switzerland). Methods: A random sample of 23000 population based subjects (aged 18-69 years) subjects participated in the survey. Results: The overall prevalence of any upper GI-symptoms (net-sum) was 38%, ranging from 24% in the Netherlands to 45% in Hungary. The prevalence of upper GI-symptoms was significantly higher in females (39%, 95%CI 38.4-39.6) vs. males (37%, 95%CI 36.4- 37.6). Heartburn was reported by 24% (95%CI 23.4-24.6). Acidic reflux and acidic stomach complaints were reported by 14% (95%CI 13.6-14.4) and 13% (95%CI 12.6-13.4) respect- ively. Other upper GI complaints labelled as “gastritis” were reported by 12% (95%CI 11.6- 12.4). There was no significant association between reported health-care seeking for the upper GI symptoms and perceived severity of symptoms. Stratified for age, significantly fewer subjects between 50-69 years reported upper GI symptoms (33.4%, 95%CI 32.3- 34.4) compared to the 18-29yr strata (42.8%, 95%CI 41.4-44.3), the 30-39yr strata (41.6%, 95%CI 40.3-43.0) and the 40-49yr strata (37.4%, 95%CI 36.1-38.7). However, in the same strata, the frequency of symptom episodes/ year reported is substantially higher (21.8 [50- 69yr] vs. 11.3 [18-29yr]-17.4 [40-49yr], p=0.001). Summary: There are marked differences in the country-specific prevalence of upper GI complaints. The reasons for this discrepancy are yet to be elucidated. In all countries, acidic reflux and heartburn are the most prevalent symptoms. Symptoms are more prevalent in females. Overall, the prevalence of upper GI symptoms decreases with age, although with age symptoms may be more frequent. 971 Abnormal Esophageal pH Study As Predictor of Treatment Response to Proton Pump Inhibitor (PPI) in Patients with Functional Dyspepsia (FD) Justin Wu, Pui Kuan Cheong, Yawen Chan, Sau Fong E. Lee, Larry Lai, Joseph J. Sung, Francis K. L. Chan BACKGROUND: Results on the efficacy of PPI for treatment of FD are conflicting. It has been postulated that PPI is only effective for dyspepsia related to gastroesophageal reflux disease (GERD). AIM: To compare the efficacy of PPI for treatment of FD between patients with and without abnormal esophageal pH study. METHODS: Consecutive patients who presented with dyspeptic symptoms that fulfilled Rome II criteria were prospectively recruited

967 Main-Duct and Combined IPMNs Are the Same Clinical Entity and Distinct from Branch-Duct IPMNs

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sreported abdominal complaints as opposed to 7.6% of those without PC(s) (p = 0.589). Noneof the individuals with PC(s) had pancreatic disease in their medical history. Conclusion: Inindividuals undergoing preventive medical examination with MRI, the prevalence of PCswas 2.2%. Of these PCs, 5.3% were ≥30 mm, 8% were multilocular and in 10% of casesmay represent side-branch IPMN. Cyst presence correlated with increasing age, no differenceof prevalence by sex was found. Abdominal complaints did not correlate with PC presence.

967

Main-Duct and Combined IPMNs Are the Same Clinical Entity and Distinctfrom Branch-Duct IPMNsStefano Crippa, Carlos Fernandez del-Castillo, Roberto Salvia, Dianne M. Finkelstein,Claudio Bassi, Ismael Dominguez, Paola Capelli, Mari Mino-Kenudson, Gregory Y.Lauwers, Massimo Falconi, Sarah P. Thayer, Stefano Partelli, Paolo Pederzoli, Andrew L.Warshaw

Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreascomprise main-duct (MD), branch-duct (BD) and combined types. There is still no consensuswhether MD- and BD-IPMNs are different points on a spectrum or altogether differentdiseases, and where combined IPMNs fit. The aim of this study was to evaluate the clinico-epidemiological characteristics and prognosis of a large series of patients with IPMNs, toelucidate differences among the three types.Methods: 389 patients who underwent pancreaticresection for a histologically confirmed IPMN were identified. Surgical specimens were re-reviewed and eventually re-classified. The clinico-pathologic characteristics of the threesubtypes were contrasted. Results: 159 (41%) patients had BD- IPMNs, 149 (38%) combinedIPMNs, and 81 (21%) MD-IPMNs. MD- and combined IPMNs occurred more frequentlyin males (56%) while BD-IPMNs were seen more often in females (57%) (p<0.05). All IPMNssubtypes were generally located in the proximal pancreas with no age differences amongdifferent IPMNs. Incidental diagnosis was more common in BD-IPMNs (34.5%) than inMD- (13.5%) and combined (19%) ones (p=0.001), while jaundice and weight loss weresignificantly more frequent in MD- and combined-IPMNs (p<0.01). Adenoma was the mostcommon histological type in BD-IPMNs (44%) and its prevalence in MD- and combinedIPMNs was significantly lower (11% and 8%, p=0.0001). Conversely the rate of invasivecancer was 11% in BD-IPMNs and 42% and 48% in combined- and MD-IPMNs (p=0.0001).Patients with combined and MD-IPMNs with invasive cancer were older than those withnoninvasive tumors -suggesting tumor progression- while this age difference was not foundin BD-IPMNs. 5-year disease specific survival was 100% for patients with noninvasive BD-IPMNs and combined-IPMNs and 95% for patients with noninvasive MD-IPMNs (one patientwho underwent total pancreatectomy for in-situ-carcinoma had peritoneal recurrence); 5-year disease specific survival was 56%, 51%, and 64%, for BD-IPMNs, MD-IPMNs, andcombined-IPMNs with invasive cancer, respectively. Conclusion: BD-IPMNs have a specificprofile, likely representing an entity distinct from other IPMNs, and combined IPMNsshow close overlapping similarities with MD-IPMNs in regard to clinico-pathological andepidemiological characteristics. Combined IPMNs should be considered an extension of MD-IPMNs to the branch-ducts, and these two subtypes show a more aggressive biologicalbehavior compared to BD-IPMNs

968

Performance Characteristics of Cyst Fluid CEA Analysis for the Diagnosis ofMucinous Cysts of the PancreasSatish Nagula, Timothy J. Kennedy, Mark A. Schattner, Murray F. Brennan, Hans Gerdes,Arnold J. Markowitz, Laura H. Tang, Peter J. Allen

Background: Elevated cyst fluid CEA levels (>200 ng/ml) have been demonstrated to behighly diagnostic of mucinous cysts of the pancreas (intraductal papillary mucinous neoplasm- IPMN, and mucinous cystic neoplasm - MCN). Methods: A prospectively maintainedpancreatic cyst registry was reviewed and 191 patients with cystic neoplasms of the pancreaswere identifiedwho had undergone endoscopic ultrasound and fine needle aspiration between2001 and 2008. All patients had cyst fluid CEA measured. Patient demographics, imagingstudies, cyst characteristics, pathology, and treatment variables were recorded. Performancecharacteristics (sensitivity, specificity, positive predictive value [PPV], negative predictivevalue [NPV]) of elevated fluid CEA (>200 ng/ml) for detecting a mucinous cyst and detectingmalignancy (in situ or invasive adenocarcinoma) were calculated in those who had a patholo-gically proven diagnoses. The outcome of patients with an elevated cyst fluid CEA who didnot undergo resection was documented. Results: A pathologically proven diagnosis wasobtained in 63 patients (33%). Mucinous neoplasms were identified in 40/63 (64%): MCN,n=9; benign IPMN, n=27; malignant IPMN, n=4. Median cyst size was 3.3 cm for non-mucinous cysts (median CEA: 117 ng/ml) and 3.0 cm for mucinous cysts (median: CEA1272 ng/ml). A cyst fluid CEA > 200 had a sensitivity, specificity, PPV, and NPV of 85%,61%, 79%, 70%, respectively, for identifying a mucinous neoplasm. The extent to whichCEA was elevated was not associated with the presence of malignancy (mean fluid CEA:mucinous malignant 7025 ng/ml, mucinous non-malignant 4271 ng/ml; p=0.52). An addi-tional 128 patients were observed (mean follow-up 24 months, range 0-120 months); 23of these patients had a cyst fluid CEA > 200 ng/ml and were followed for more than 12months. None of these patients developed radiographic changes that resulted in surgicalresection. Cyst fluid CEA was not associated with cyst growth, even amongst the subset ofpatients with elevated cyst fluid CEA and extended followup. Conclusions: In this study,cyst fluid CEA > 200 ng/ml was found to have a PPV of 79% and NPV of 70% for identifyingmucinous neoplasms. In contrast to prior published reports, this registry contains a largenumber of IPMNs, and demonstrates that CEA has similar efficacy for the diagnosis of bothMCN and IPMN. Elevation of cyst fluid CEA was not associated with malignancy, or ahigher likelihood of cyst growth. Better markers for identifying dysplasia in mucinous cystsand predicting cyst behavior are needed to aid in management.

A-148AGA Abstracts

969

Proteomic Analysis of Cyst Fluid Mucin Expression Is Significantly MoreAccurate Than Conventional Cyst Fluid Analyses in the Clinical Assessmentof Pancreatic Cystic LesionsKarolina Sjöberg, Malin E. Johansson, Anders G. Hyltander, Evangelos Kalaitzakis,Morteza Shafazand, Jan Hansen, Henrik Sjovall, Gunnar C. Hansson, Riadh Sadik

The assessment of pancreatic cystic lesions (PCL) - the detection and staging of cystic/cyst-like tumors (CT) - is a clinical challenge. Mucin expression has been observed in mucinousand serous CTs and in ductal adenocarcinomas (that may appear cyst-like), but not inpseudocysts. Ductal adenocarcinomas exhibit MUC1 overexpression, which, when seen inmucinous CTs, supposedly indicates invasive disease. However, prospective studies arelacking, as are studies that use proteomics and thus avoid the diagnostic pitfall of differentialmucin glycosylation. AIMS: To explore the utility of proteomic analysis of cyst fluid mucinexpression, in the clinical assessment of PCLs. METHODS: Patients referred for endoscopicultrasound with fine needle aspiration of a PCL were prospectively included. Cytology withPAS diastase mucus stain, and cyst fluid CEA quantification were performed. Cyst fluidsamples (~20μl) were then run on a gel electrophoresis; high mass bands were cut out,trypsinized and analyzed by nanoLC-mass spectrometry and MS/MS on an FT mass spectro-meter. For peptide identification the Mascot software and an in-house mucin database wereused. Primary diagnostic endpoints: 1)Surgical pathology (n=8); 2)Follow-up includingimaging (n=12); 3)Preliminary diagnosis, based on all clinical data except proteomics results(blinded) (n=9). RESULTS: 13 females and 16 males were included, age range 36-86, median64. According to our primary diagnostic endpoints there were 19 CTs and 10 pseudocysts.We compared the sensitivity, specificity and accuracy for detection of CTs, for proteomicmucin expression analysis and cytology (Table 1). In line with earlier reports, 2/3 serousCTs expressed MUC6 alone, a pattern not seen for other PCLs. The diagnostic utility ofCEA was flawed by a lack of results for 10/29 PCLs due to low cyst fluid yield. For thecases with a surgical pathology, we compared the capacity for preoperative detection ofmalignancy, for proteomics (presence/absence of MUC1 expression) and cytology. Sensitivitywas 57% for proteomics and 13% for cytology; specificity 100% for both. CONCLUSION:Proteomic mucin expression analysis was significantly more accurate than standard cystfluid analyses in the clinical assessment of PCLs. MUC1 expression was more sensitive thancytology as a marker for malignancy.Minute amounts of cyst fluid are required for proteomics,whereas cyst fluid yield may restrict the diagnostic utility of CEA.Table 1

Cyst fluid CEA (cut-off 400ng/ml): Sensitivity:50% Specificity:89%

970

A 13-Nation Population Survey of Upper Gastrointestinal Symptoms: Age andGenderSebastian Haag, Jane M. Andrews, Judith D. Gapasin, Andreas Keller, Gerald Holtmann

Background: There is a lack of studies which assess and compare the prevalence of uppergastrointestinal (GI) symptoms contemporaneously in various countries using a uniform,standardised method. Previous data collected in separate studies using various differentsurvey instruments have suggested some variability in the prevalence of symptoms betweennations. Thus the aim of this study was to determine the prevalence of upper GI symptomsin 13 European countries (Austria, Belgium, Denmark, Finland, France, Germany, Hungary,Italy, Netherlands, Poland, Portugal, Spain, and Switzerland). Methods: A random sampleof 23000 population based subjects (aged 18-69 years) subjects participated in the survey.Results: The overall prevalence of any upper GI-symptoms (net-sum) was 38%, rangingfrom 24% in the Netherlands to 45% in Hungary. The prevalence of upper GI-symptomswas significantly higher in females (39%, 95%CI 38.4-39.6) vs. males (37%, 95%CI 36.4-37.6). Heartburn was reported by 24% (95%CI 23.4-24.6). Acidic reflux and acidic stomachcomplaints were reported by 14% (95%CI 13.6-14.4) and 13% (95%CI 12.6-13.4) respect-ively. Other upper GI complaints labelled as “gastritis” were reported by 12% (95%CI 11.6-12.4). There was no significant association between reported health-care seeking for theupper GI symptoms and perceived severity of symptoms. Stratified for age, significantlyfewer subjects between 50-69 years reported upper GI symptoms (33.4%, 95%CI 32.3-34.4) compared to the 18-29yr strata (42.8%, 95%CI 41.4-44.3), the 30-39yr strata (41.6%,95%CI 40.3-43.0) and the 40-49yr strata (37.4%, 95%CI 36.1-38.7). However, in the samestrata, the frequency of symptom episodes/ year reported is substantially higher (21.8 [50-69yr] vs. 11.3 [18-29yr]-17.4 [40-49yr], p=0.001). Summary: There are marked differencesin the country-specific prevalence of upper GI complaints. The reasons for this discrepancyare yet to be elucidated. In all countries, acidic reflux and heartburn are the most prevalentsymptoms. Symptoms are more prevalent in females. Overall, the prevalence of upper GIsymptoms decreases with age, although with age symptoms may be more frequent.

971

Abnormal Esophageal pH Study As Predictor of Treatment Response to ProtonPump Inhibitor (PPI) in Patients with Functional Dyspepsia (FD)Justin Wu, Pui Kuan Cheong, Yawen Chan, Sau Fong E. Lee, Larry Lai, Joseph J. Sung,Francis K. L. Chan

BACKGROUND: Results on the efficacy of PPI for treatment of FD are conflicting. It hasbeen postulated that PPI is only effective for dyspepsia related to gastroesophageal refluxdisease (GERD). AIM: To compare the efficacy of PPI for treatment of FD between patientswith and without abnormal esophageal pH study. METHODS: Consecutive patients whopresented with dyspeptic symptoms that fulfilled Rome II criteria were prospectively recruited