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S1305 Does Fluid CEA Level Predict Malignancy in Intraductal Papillary Mucinous Neoplasms (IPMNs)?
of patients with indeterminant pancreatic cysts. Methods: We retrospectively analyzed our tertiary care referral center's experience with EUS-FNA of pancreatic cysts. Medical records of patients who had more than one EUS-FNA from 2003 to 2007 were reviewed. Cyst size, location, CEA level, cytopathology and interval between EUS-FNA examinations were recorded. For each patient, cyst diagnosis was determined by surgical pathology (when available) or via established criteria for diagnosis of mucinous cystic neoplasms by cyst fluid chemistry (CEA >192 ng/mL) and/or cytopathologic analysis. Results: 197 patients underwent EUS-FNA for the evaluation of a pancreatic cyst, of which 31 (16%) had more than one examination. A total of 71 exams were performed in these patients. Repeat EUS-FNA led to a new diagnosis in 9 patients (29%). Two were found to have a malignancy, 4 patients had a pseudocyst, 2 patients had a mucinous cystic neoplasm and 1 patient had a serous cystadenoma. The average interval between exams among patients in which a repeat EUSFNA made a diagnostic difference was 20.6 vs. 13.0 months in those in which it did not (p=0.15). Pancreatic cysts increased in size by, on average, 0.53cm/yr +/- 0.82 cm among patients in which repeat EUS-FNA made a definitive diagnosis. In patients where the initial EUS-FNA was non-diagnostic, insufficient cyst fluid aspiration was noted in comparison to those in whom a definitive diagnosis was made (33% vs.72%p=0.056). Conclusion: This is the first study, to our knowledge, to evaluate the role of repeat EUS-FNA for the definitive diagnosis of indeterminant pancreatic cysts. In our small sample, repeat EUS-FNA led to a clear diagnosis in 29% of patients. Although the statistical power of this study is limited, it appears that repeat EUS-FNA should be considered in patients who have a cyst increasing in size or if insufficient cyst fluid was aspirated initially to quantify a CEA level.
appear to have a significant association with extra pancreatic cancers and should undergo a comprehensive screening process for early detection of these cancers.
Prognostic Factors in Surgically Resected Pancreatic Cysts Michelle K. Kim, Thomas Curran, Amir Soumekh, Daniel Labow, Myron E. Schwartz, Noam Harpaz, Steven H. Itzkowitz Background and Aims: Pancreatic cysts manifest varying degrees of malignant potential. Since our ability to distinguish between benign, premalignant and malignant pancreatic cystic lesions is limited, surgical resection is often advised. Because surgical resection carries substantial morbidity and mortality, accurate preoperative diagnosis is of great importance. The aim of this study was to identify preoperative features that correlate with malignant potential of surgically resected pancreatic cysts and to analyze the association of clinicopathologic features with survival. Methods: A retrospective review was conducted of all pancreatic cyst surgical resections performed at The Mount Sinai Hospital from August 1995 to June 2006. Cysts were categorized by histopathology as benign (n=35), premalignant (n=22), or malignant (n=17). Pseudocysts were excluded from analysis. Results: Mean age was 60.6 years (25.0 to 81.2 years). Approximately 68% of patients were female. Cysts were detected incidentally in 37.5% of cases. One in seven patients underwent surgical resections for asymptomatic, benign disease. Patients with malignant cysts were more likely to be older (OR=1.051, 95% CI: 1.004 - 1.101), to have lesions in the head of the pancreas (OR= 10.045, 95% CI: 2.708 - 37.258), to have large cysts (>3cm) (OR=6.627, 95% CI: 1.640 - 26.777) and to have pancreatic duct dilation (OR=6.417, 95% CI: 1.397 - 29.470). On multivariate analysis, older age (HR=1.155, 95% CI: 1.038 - 1.285) and malignant pathology (HR=5.721, 95% CI: 1.268 - 25.808) were independent predictors of decreased survival (Figure 1). Conclusions: Older age, location in head of pancreas, larger cyst size and pancreatic duct dilation were associated with malignancy. Malignant pathology and older age were associated with shorter survival. Given the significant percentage of patients who undergo resection for asymptomatic, benign disease, these factors may help create a strategy to identify low risk patients and avoid unnecessary surgical resection.
S1302 Synchronous Intraductal Papillary Mucinous Neoplasm and Autoimmune Pancreatitis: An Original Association Maria C. Petrone, Paolo G. Arcidiacono, Silvia Carrara, Antonella Giussani, Cinzia Boemo, Luca Albarello, Claudio Doglioni, Pier A. Testoni BACKGROUND Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis characterized by a mixed inflammatory infiltrate centered around the pancreatic ducts accompanied by an obliterative venulitis, and interstitial fibrosis.The clinical presentation and diagnostic imaging of AIP can mimic infiltrating pancreatic ductal adenocarcinoma (PDA) and traditionally, differentiation from a neoplasm has been made by examination of pathologic specimens after surgical resection.Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts.To our knowledge, in literature is reported only one case about synchronous AIP and IPMN.The aim of this retrospective study was to evaluate the association of occasional histologic diagnosis of AIP in those patients who underwent pancreatic surgical resection for an IPMN. METHODS We enrolled patients referred to our tertiary university center, who underwent pancreatic resection for an IPMN from January 2007 to October 2008.Exclusion criteria was absence of preliminary cytologic diagnosis.The specimens were reviewed by a single experienced pathologist.Each specimen was assessed for the presence of synchronous AIP and IPMN. RESULTS During the study period we registered 118 new endoscopic ultrasound (EUS) diagnosis of IPMN.EUS-guided fine needle aspiration (FNA) was performed in 59.3% of patients (70/118). Overall, 16 patients (median age 61.6, 11 males) underwent pancreatic resection because of the EUS findings and the presence of atypical cells at cytology examination of FNA (13 Whipple resection, 3 distal pancreasectomy). The lesion mean size was 27.8±7 mm. The final histological diagnosis was PDA arised from an IPMN in five cases, IPMN with pancreatic intraepithelial neoplasia (PanIN) type 2 in eight cases and IPMN with PanIN 1 in three cases.In 4 specimens (25%) AIP was also present: there was an intense mixed inflammatory cell infiltrate predominantly composed of lymphocytes and plasma cells centered on the pancreatic ducts, associated with parenchymal fibrosis.All of them were associated with PanIN. CONCLUSIONS In the last years AIP has been increasingly diagnosed, as well as IPMN. However, we reported for the first time to our knowledge, a short series of patients with association of these conditions. In a relevant percentage of IPMNs underwent to surgery there was sinchronous AIP. Further prospective studies are needed to explain if this association is indipendent or if there are any factors that are related to both entities.
S1305 Does Fluid CEA Level Predict Malignancy in Intraductal Papillary Mucinous Neoplasms (IPMNs)? Daniela Scimeca, Kanwar R. Gill, Murli Krishna, Timothy A. Woodward, Michael B. Wallace, John Stauffer, Justin H. Nguyen, Laith H. Jamil, Massimo Raimondo Background & Aims: IPMNs have a variable potential for evolving to malignancy. Main duct involvement, mural nodules, cysts >30 mm and positive cytology are predictive factors of progression to malignancy. EUS allows fluid sampling from these cysts. Recently, Maire et al. (AJG 2008) showed that intracystic CEA >200 ng/dl had a sensitivity and specificity of 90 and 71% respectively, for the diagnosis of malignant IPMN. The purpose of this study was to evaluate the role of fluid CEA obtained by EUS-FNA in differentiating benign from malignant IPMNs. Methods: Retrospectively, we identified all patients who underwent surgery between 01/02 and 08/08, with a pathological diagnosis of IPMNs. Among these, we selected patients with a pre-operative evaluation by EUS-FNA and cystic fluid CEA. The results of CEA were compared with corresponding histopathology according to the WHO criteria. Patients were classified as having benign vs. malignant and non invasive vs. invasive disease. Results: One hundred and three patients (42 males; mean age 68.5 yrs) with 60 (58%) benign and 43 (42%) malignant IPMNs and 76 (74%) non invasive and 27 (26%) invasive disease were identified. Ninety-five (92%) underwent EUS. Cystic fluid CEA was available in 35 of 71 (49%) patients who underwent EUS-FNA, including benign (n=21) and malignant (n=14) or non invasive (n=28) and invasive (n=7) IPMNs, respectively. The mean CEA was 1598.6 (range 2.8-5414 ng/ml) in the benign group vs. 5472.6 (range 11-56990 ng/ml) in the malignant group, respectively without significant difference between two groups (p= 0.2). The mean CEA was 3658.1 (range 2.8-56990 ng/ml) in the non invasive group and 1108.8 (range 215-4266 ng/ml) in the invasive group, respectively without significant difference between two groups (p=0.5). Using a value of 821 ng/dl (obtained by a ROC curve) as arbitrary cut-off between benign and malignant tumors, we obtained a sensitivity, specificity, PPV, NPV and accuracy of 71%, 57%, 53%, 75%, and 63% respectively. Using a value of 1000 ng/dl as arbitrary cut-off between non invasive and invasive, we obtained a sensitivity, specificity, PPV, NPV and accuracy of 86%, 43%, 27%, 92%, and 51%, respectively. Conclusions: Our study does not support the role of intracystic CEA level to discriminate benign from malignant or non invasive from invasive IPMNs. Caution should therefore be used when using fluid CEA levels for clinical decision making. Prospective studies are recommended to evaluate its role in IPMNs in combination with other molecular markers.
S1303 Old Age, Male Sex and Family History of Cancer in Those with IPMN Has An Increased Association with Extra Pancreatic Malignancy Samuel A. Giday, Shivangi Kothari, David B. Liang, Anthony N. Kalloo, Sanjay B. Jagannath, Marcia I. Canto A small number of published series have suggested an increased association of IPMNs with other extra pancreatic neoplasms. Aim: To assess the frequency and predictors of extra pancreatic malignancy in patients with histologically proven IPMNs. Methods: Clinical information including personal and family history of malignancy, radiographic studies and endoscopic ultrasound (EUS) data from patients with resected IPMNs at a large tertiary referral center were analyzed. The frequency of extra pancreatic malignancy was determined. The extent of pancreatic disease (i.e. unifocal vs. multifocal) along with other variables were also noted and compared between the two groups. Historical population controls were used for comparison of cancer frequency. Results: One hundred thirty four patients with resected IPMNs had data available for the study. History of extra pancreatic malignancy was found in 38 (28%) of the patients. Of the patients with extra pancreatic malignancy, multifocal IPMN was noted in 20 patients (59%). A total of 50 cancers were found in those 38 patients. Skin cancer (Basal cell cancer) was the most frequent cancer diagnosed in our patients (26%) followed by prostate (18%), renal cell cancer (16%) and colon cancer (8%). Other cancers diagnosed in these patients included breast, lung, hepatocellular, duodenal carcinoid and connective tissue tumor. Family history of malignancy was found in majority of the patients in our study (68%). Patients with extra pancreatic malignancy were more likely to be men, older (mean 72 years) and have a family history of malignancy (P<0.05). The presence of multifocal disease and size was not different between patients with and without extra pancreatic cancers. Conclusion: A third of patients (28%) with IPMN were found to have a second extra pancreatic cancer. Older men with a positive family history and IPMNs
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AGA Abstracts
AGA Abstracts
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appear to have a significant association with extra pancreatic cancers and should undergo a comprehensive screening process for early detection of these cancers.
Prognostic Factors in Surgically Resected Pancreatic Cysts Michelle K. Kim, Thomas Curran, Amir Soumekh, Daniel Labow, Myron E. Schwartz, Noam Harpaz, Steven H. Itzkowitz Background and Aims: Pancreatic cysts manifest varying degrees of malignant potential. Since our ability to distinguish between benign, premalignant and malignant pancreatic cystic lesions is limited, surgical resection is often advised. Because surgical resection carries substantial morbidity and mortality, accurate preoperative diagnosis is of great importance. The aim of this study was to identify preoperative features that correlate with malignant potential of surgically resected pancreatic cysts and to analyze the association of clinicopathologic features with survival. Methods: A retrospective review was conducted of all pancreatic cyst surgical resections performed at The Mount Sinai Hospital from August 1995 to June 2006. Cysts were categorized by histopathology as benign (n=35), premalignant (n=22), or malignant (n=17). Pseudocysts were excluded from analysis. Results: Mean age was 60.6 years (25.0 to 81.2 years). Approximately 68% of patients were female. Cysts were detected incidentally in 37.5% of cases. One in seven patients underwent surgical resections for asymptomatic, benign disease. Patients with malignant cysts were more likely to be older (OR=1.051, 95% CI: 1.004 - 1.101), to have lesions in the head of the pancreas (OR= 10.045, 95% CI: 2.708 - 37.258), to have large cysts (>3cm) (OR=6.627, 95% CI: 1.640 - 26.777) and to have pancreatic duct dilation (OR=6.417, 95% CI: 1.397 - 29.470). On multivariate analysis, older age (HR=1.155, 95% CI: 1.038 - 1.285) and malignant pathology (HR=5.721, 95% CI: 1.268 - 25.808) were independent predictors of decreased survival (Figure 1). Conclusions: Older age, location in head of pancreas, larger cyst size and pancreatic duct dilation were associated with malignancy. Malignant pathology and older age were associated with shorter survival. Given the significant percentage of patients who undergo resection for asymptomatic, benign disease, these factors may help create a strategy to identify low risk patients and avoid unnecessary surgical resection.
S1302 Synchronous Intraductal Papillary Mucinous Neoplasm and Autoimmune Pancreatitis: An Original Association Maria C. Petrone, Paolo G. Arcidiacono, Silvia Carrara, Antonella Giussani, Cinzia Boemo, Luca Albarello, Claudio Doglioni, Pier A. Testoni BACKGROUND Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis characterized by a mixed inflammatory infiltrate centered around the pancreatic ducts accompanied by an obliterative venulitis, and interstitial fibrosis.The clinical presentation and diagnostic imaging of AIP can mimic infiltrating pancreatic ductal adenocarcinoma (PDA) and traditionally, differentiation from a neoplasm has been made by examination of pathologic specimens after surgical resection.Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts.To our knowledge, in literature is reported only one case about synchronous AIP and IPMN.The aim of this retrospective study was to evaluate the association of occasional histologic diagnosis of AIP in those patients who underwent pancreatic surgical resection for an IPMN. METHODS We enrolled patients referred to our tertiary university center, who underwent pancreatic resection for an IPMN from January 2007 to October 2008.Exclusion criteria was absence of preliminary cytologic diagnosis.The specimens were reviewed by a single experienced pathologist.Each specimen was assessed for the presence of synchronous AIP and IPMN. RESULTS During the study period we registered 118 new endoscopic ultrasound (EUS) diagnosis of IPMN.EUS-guided fine needle aspiration (FNA) was performed in 59.3% of patients (70/118). Overall, 16 patients (median age 61.6, 11 males) underwent pancreatic resection because of the EUS findings and the presence of atypical cells at cytology examination of FNA (13 Whipple resection, 3 distal pancreasectomy). The lesion mean size was 27.8±7 mm. The final histological diagnosis was PDA arised from an IPMN in five cases, IPMN with pancreatic intraepithelial neoplasia (PanIN) type 2 in eight cases and IPMN with PanIN 1 in three cases.In 4 specimens (25%) AIP was also present: there was an intense mixed inflammatory cell infiltrate predominantly composed of lymphocytes and plasma cells centered on the pancreatic ducts, associated with parenchymal fibrosis.All of them were associated with PanIN. CONCLUSIONS In the last years AIP has been increasingly diagnosed, as well as IPMN. However, we reported for the first time to our knowledge, a short series of patients with association of these conditions. In a relevant percentage of IPMNs underwent to surgery there was sinchronous AIP. Further prospective studies are needed to explain if this association is indipendent or if there are any factors that are related to both entities.
S1305 Does Fluid CEA Level Predict Malignancy in Intraductal Papillary Mucinous Neoplasms (IPMNs)? Daniela Scimeca, Kanwar R. Gill, Murli Krishna, Timothy A. Woodward, Michael B. Wallace, John Stauffer, Justin H. Nguyen, Laith H. Jamil, Massimo Raimondo Background & Aims: IPMNs have a variable potential for evolving to malignancy. Main duct involvement, mural nodules, cysts >30 mm and positive cytology are predictive factors of progression to malignancy. EUS allows fluid sampling from these cysts. Recently, Maire et al. (AJG 2008) showed that intracystic CEA >200 ng/dl had a sensitivity and specificity of 90 and 71% respectively, for the diagnosis of malignant IPMN. The purpose of this study was to evaluate the role of fluid CEA obtained by EUS-FNA in differentiating benign from malignant IPMNs. Methods: Retrospectively, we identified all patients who underwent surgery between 01/02 and 08/08, with a pathological diagnosis of IPMNs. Among these, we selected patients with a pre-operative evaluation by EUS-FNA and cystic fluid CEA. The results of CEA were compared with corresponding histopathology according to the WHO criteria. Patients were classified as having benign vs. malignant and non invasive vs. invasive disease. Results: One hundred and three patients (42 males; mean age 68.5 yrs) with 60 (58%) benign and 43 (42%) malignant IPMNs and 76 (74%) non invasive and 27 (26%) invasive disease were identified. Ninety-five (92%) underwent EUS. Cystic fluid CEA was available in 35 of 71 (49%) patients who underwent EUS-FNA, including benign (n=21) and malignant (n=14) or non invasive (n=28) and invasive (n=7) IPMNs, respectively. The mean CEA was 1598.6 (range 2.8-5414 ng/ml) in the benign group vs. 5472.6 (range 11-56990 ng/ml) in the malignant group, respectively without significant difference between two groups (p= 0.2). The mean CEA was 3658.1 (range 2.8-56990 ng/ml) in the non invasive group and 1108.8 (range 215-4266 ng/ml) in the invasive group, respectively without significant difference between two groups (p=0.5). Using a value of 821 ng/dl (obtained by a ROC curve) as arbitrary cut-off between benign and malignant tumors, we obtained a sensitivity, specificity, PPV, NPV and accuracy of 71%, 57%, 53%, 75%, and 63% respectively. Using a value of 1000 ng/dl as arbitrary cut-off between non invasive and invasive, we obtained a sensitivity, specificity, PPV, NPV and accuracy of 86%, 43%, 27%, 92%, and 51%, respectively. Conclusions: Our study does not support the role of intracystic CEA level to discriminate benign from malignant or non invasive from invasive IPMNs. Caution should therefore be used when using fluid CEA levels for clinical decision making. Prospective studies are recommended to evaluate its role in IPMNs in combination with other molecular markers.
S1303 Old Age, Male Sex and Family History of Cancer in Those with IPMN Has An Increased Association with Extra Pancreatic Malignancy Samuel A. Giday, Shivangi Kothari, David B. Liang, Anthony N. Kalloo, Sanjay B. Jagannath, Marcia I. Canto A small number of published series have suggested an increased association of IPMNs with other extra pancreatic neoplasms. Aim: To assess the frequency and predictors of extra pancreatic malignancy in patients with histologically proven IPMNs. Methods: Clinical information including personal and family history of malignancy, radiographic studies and endoscopic ultrasound (EUS) data from patients with resected IPMNs at a large tertiary referral center were analyzed. The frequency of extra pancreatic malignancy was determined. The extent of pancreatic disease (i.e. unifocal vs. multifocal) along with other variables were also noted and compared between the two groups. Historical population controls were used for comparison of cancer frequency. Results: One hundred thirty four patients with resected IPMNs had data available for the study. History of extra pancreatic malignancy was found in 38 (28%) of the patients. Of the patients with extra pancreatic malignancy, multifocal IPMN was noted in 20 patients (59%). A total of 50 cancers were found in those 38 patients. Skin cancer (Basal cell cancer) was the most frequent cancer diagnosed in our patients (26%) followed by prostate (18%), renal cell cancer (16%) and colon cancer (8%). Other cancers diagnosed in these patients included breast, lung, hepatocellular, duodenal carcinoid and connective tissue tumor. Family history of malignancy was found in majority of the patients in our study (68%). Patients with extra pancreatic malignancy were more likely to be men, older (mean 72 years) and have a family history of malignancy (P<0.05). The presence of multifocal disease and size was not different between patients with and without extra pancreatic cancers. Conclusion: A third of patients (28%) with IPMN were found to have a second extra pancreatic cancer. Older men with a positive family history and IPMNs
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AGA Abstracts
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