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Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: Risk of malignancy and concomitant ductal adenocarcinoma
Abstracts / Pancreatology 13 (2013) e1–e94
secretin increased cAMP formation from WT mice pancreatic ducts up to 22-fold and 8-fold, respectively. The VIP-induced cAMP generation was reduced by 56 % in AC6 KO mice. Conclusion: This study demonstrates a role for AC6 in pancreatic exocrine cells: AC6 is required for cAMP generation in both acini and ducts and for amylase secretion.
P204. Stent-related complications of endotherapy in the treatment of chronic pancreatitis pain and their relationship to the duration of stent placement J. Sadiq, M. Jafri, D. Lee, F. Gress. Dept. of Gastroenterology, SUNY Downstate, Brooklyn, NY, USA Background: Chronic pancreatitis (CP) pain is difficult to manage due its wide array of etiologies and available therapies. Surgery (SX) and endotherapy (ET) are the most commonly used modalities. Recent data has favored the use of ET over SX due to its less invasive nature and fewer complications. This study analyzes the stent related complications of ET (i.e. stent migration (SM) and stent occlusion (SO)) based on definitive stent placement duration. Methods: A search of Pubmed was made from 1991-2010 for studies that used ET for pain relief due to CP. Exclusion criteria were: studies not in English, studies with <10 patients, case series, studies which did not clearly state the stent-related complications, and studies that utilized alternative therapies, such as SX or celiac plexus neurolysis. The data on complications was then extracted with focus on subgroups based on the definitive duration of stent treatment (6 months vs. >6 months). Results: After using the exclusion criteria, 10 studies were obtained with a total of 601 patients. The total number of ERCP procedures in the 10 studies was then aggregated, totaling 1760. The studies were divided into the aforementioned subsets 6 months vs. >6 months, based on the definitive duration of stent therapy. The results for the group with 6 months (n¼248, 758 ERCP procedures) showed a SO rate of 7.65% and a SM rate of 2.9%. The group with a treatment duration >6 month (n¼353, 1002 ERCP procedures) showed a SO rate of 1.49% and SM rate of 1.20%. P values as follows: Migration: P¼ 0.0168. Occlusion: P < 0.0001. Conclusion: ET has a complication rate of approx. 7.85%. The most commonly reported stent related complications include SM and SO. Our analysis shows that longer stent duration placement (>6 months) is associated with fewer number of stent related complications (6 months 10.55% vs. >6, 2.69% respectively). Larger well-designed RCT are needed to verify this finding.
P205. GNAS and KRAS mutations in multifocal intraductal papillary mucinous neoplasms (IPMN) of the pancreas – Pilot study K. Sahora 1, D. Dias-Santagata 2, V. Morales-Oyarvide 2, L.A. Bernardo 2, A.J. Iafrate 2, M.B. Pitman 2, C. Fernandez-del Castillo 1, M. Mino-Kenudson 2. 1 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA 2 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA Background: IPMN are increasingly diagnosed cystic precursor lesions of pancreatic ductal adenocarcinoma (PDAC) and consist of 4 epithelial subtypes. IPMN can be multifocal, and the majority of multifocal IPMN (mIPMN) are composed of branch duct lesions exhibiting gastric-type epithelium (IPMN-G) with low- or intermediate-grade dysplasia. They are also at a higher risk of developing concurrent PDAC. These features are similar to those of pancreatic intraepithelial neoplasia (PanIN). KRAS mutations reportedly occur frequently in both IPMN and PanIN. Recent reports demonstrated the frequent GNAS mutations in IPMN, especially in the intestinal type (IPMN-I), and the almost complete absence of GNAS mutations
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in PanIN and conventional PDAC. The aim of this pilot study was to compare molecular alterations of mIPMN with those of single, predominantly branch-duct type IPMN with low- or intermediate-grade dyspasia. Methods: KRAS and GNAS mutations are evaluated on FFPE tissue samples of the surgically resected IPMN lesions using a SNaPshot platform: 6 mIPMN (gastric type, one with a concurrent PDAC), 6 IPMN-G and 5 IPMN-I. Results: GNAS mutations were identified in 4 (67%) mIPMN, 4 (67%) IPMN-G, and 4 (80%) IPMN-I, KRAS mutations in 5 (83%) mIPMN, 4 (67%) IPMN-G, and 1 (20%) IPMN-I. Three (50%) mIPMN, 4 (67%) IPMN-G and 1 (20%) IPMN-I harbored concurrent KRAS and GNAS mutations. Interestingly, the mIPMN with a concurrent PDAC exhibited distinct KRAS mutations in the 2 foci with no GNAS mutations. Conclusion: The results indicate that, irrespective of focality, IPMN-G tend to harbor both GNAS and KRAS mutations and are distinct from PanIN at their molecular level. If confirmed in a larger cohort study (underway), the findings may have significant implications in pre-operative diagnosis with cyst fluid analysis.
P206. Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: Risk of malignancy and concomitant ductal adenocarcinoma K. Sahora 1, M. Mino-Kenudson 2, S.P. Thayer 1, C. Ferrone 1, J. Wargo 1, A.L. Warshaw 1, K. Lillemoe 1, C. Fernandez-del Castillo 2. 1 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA 2 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA Background: The natural history of branch duct IPMN is still largely unknown. The aim of this study was to review the risk of malignancy in branch duct IPMNs in a large single center cohort. Methods: A review of 482 patients with branch duct (BD) IPMN diagnosed between 1995 and 2012 was performed. Patients who underwent primary resection with histopathological confirmation of BD-IPMN, as well as patients being followed with BD-IPMN 1.5 cm for a minimum of one year were included. Results: 331 patients met the above criteria ; 182 (55%) patients underwent primary resection and 149 (45%) were followed (median 42 months, and 61 (41%) for >5 years). Of patients who were primarily followed, 22 (14.8%) underwent surgery because of concerning findings or symptoms (median time to surgery: 21 months, 7-126 m), and only 2 (9% of resected and 1.3% of the cohort) were malignant. Pathology of all the resected cases showed BD-IPMN adenoma in 45% (91/204), borderline tumor in 35% , carcinoma in situ in 10% and invasive cancer in 10% (20/204). Concomitant pancreatic ductal adenocarcinoma (PDAC) (i.e distant from the IPMN) was found in 8 patients (2.4%), all of which were resected. One of these patients had been followed 10 years for a presumed branch duct IPMN. Conclusion: Risk of malignancy in resected IPMN is around 20%, and the risk of concomitant PDAC low (2.4%). Expectant management of patients who do not meet criteria for resection is safe, although the high frequency of borderline tumors (35%) in resected patients and the relatively short median follow-up (42 months) preclude definitive conclusions on the long-term safety of this approach.
P207. Radiologic assessment of pancreatic disease (RAPiD) study: Association of quantitative MRI features with pancreas secretory function in suspected chronic pancreatitis N.I. Sainani, P.A. Banks, L.S. Lee, V. Kadiyala, S.L. Suleiman, D.L. Conwell. Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, MA, USA
secretin increased cAMP formation from WT mice pancreatic ducts up to 22-fold and 8-fold, respectively. The VIP-induced cAMP generation was reduced by 56 % in AC6 KO mice. Conclusion: This study demonstrates a role for AC6 in pancreatic exocrine cells: AC6 is required for cAMP generation in both acini and ducts and for amylase secretion.
P204. Stent-related complications of endotherapy in the treatment of chronic pancreatitis pain and their relationship to the duration of stent placement J. Sadiq, M. Jafri, D. Lee, F. Gress. Dept. of Gastroenterology, SUNY Downstate, Brooklyn, NY, USA Background: Chronic pancreatitis (CP) pain is difficult to manage due its wide array of etiologies and available therapies. Surgery (SX) and endotherapy (ET) are the most commonly used modalities. Recent data has favored the use of ET over SX due to its less invasive nature and fewer complications. This study analyzes the stent related complications of ET (i.e. stent migration (SM) and stent occlusion (SO)) based on definitive stent placement duration. Methods: A search of Pubmed was made from 1991-2010 for studies that used ET for pain relief due to CP. Exclusion criteria were: studies not in English, studies with <10 patients, case series, studies which did not clearly state the stent-related complications, and studies that utilized alternative therapies, such as SX or celiac plexus neurolysis. The data on complications was then extracted with focus on subgroups based on the definitive duration of stent treatment (6 months vs. >6 months). Results: After using the exclusion criteria, 10 studies were obtained with a total of 601 patients. The total number of ERCP procedures in the 10 studies was then aggregated, totaling 1760. The studies were divided into the aforementioned subsets 6 months vs. >6 months, based on the definitive duration of stent therapy. The results for the group with 6 months (n¼248, 758 ERCP procedures) showed a SO rate of 7.65% and a SM rate of 2.9%. The group with a treatment duration >6 month (n¼353, 1002 ERCP procedures) showed a SO rate of 1.49% and SM rate of 1.20%. P values as follows: Migration: P¼ 0.0168. Occlusion: P < 0.0001. Conclusion: ET has a complication rate of approx. 7.85%. The most commonly reported stent related complications include SM and SO. Our analysis shows that longer stent duration placement (>6 months) is associated with fewer number of stent related complications (6 months 10.55% vs. >6, 2.69% respectively). Larger well-designed RCT are needed to verify this finding.
P205. GNAS and KRAS mutations in multifocal intraductal papillary mucinous neoplasms (IPMN) of the pancreas – Pilot study K. Sahora 1, D. Dias-Santagata 2, V. Morales-Oyarvide 2, L.A. Bernardo 2, A.J. Iafrate 2, M.B. Pitman 2, C. Fernandez-del Castillo 1, M. Mino-Kenudson 2. 1 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA 2 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA Background: IPMN are increasingly diagnosed cystic precursor lesions of pancreatic ductal adenocarcinoma (PDAC) and consist of 4 epithelial subtypes. IPMN can be multifocal, and the majority of multifocal IPMN (mIPMN) are composed of branch duct lesions exhibiting gastric-type epithelium (IPMN-G) with low- or intermediate-grade dysplasia. They are also at a higher risk of developing concurrent PDAC. These features are similar to those of pancreatic intraepithelial neoplasia (PanIN). KRAS mutations reportedly occur frequently in both IPMN and PanIN. Recent reports demonstrated the frequent GNAS mutations in IPMN, especially in the intestinal type (IPMN-I), and the almost complete absence of GNAS mutations
e69
in PanIN and conventional PDAC. The aim of this pilot study was to compare molecular alterations of mIPMN with those of single, predominantly branch-duct type IPMN with low- or intermediate-grade dyspasia. Methods: KRAS and GNAS mutations are evaluated on FFPE tissue samples of the surgically resected IPMN lesions using a SNaPshot platform: 6 mIPMN (gastric type, one with a concurrent PDAC), 6 IPMN-G and 5 IPMN-I. Results: GNAS mutations were identified in 4 (67%) mIPMN, 4 (67%) IPMN-G, and 4 (80%) IPMN-I, KRAS mutations in 5 (83%) mIPMN, 4 (67%) IPMN-G, and 1 (20%) IPMN-I. Three (50%) mIPMN, 4 (67%) IPMN-G and 1 (20%) IPMN-I harbored concurrent KRAS and GNAS mutations. Interestingly, the mIPMN with a concurrent PDAC exhibited distinct KRAS mutations in the 2 foci with no GNAS mutations. Conclusion: The results indicate that, irrespective of focality, IPMN-G tend to harbor both GNAS and KRAS mutations and are distinct from PanIN at their molecular level. If confirmed in a larger cohort study (underway), the findings may have significant implications in pre-operative diagnosis with cyst fluid analysis.
P206. Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: Risk of malignancy and concomitant ductal adenocarcinoma K. Sahora 1, M. Mino-Kenudson 2, S.P. Thayer 1, C. Ferrone 1, J. Wargo 1, A.L. Warshaw 1, K. Lillemoe 1, C. Fernandez-del Castillo 2. 1 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA 2 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA Background: The natural history of branch duct IPMN is still largely unknown. The aim of this study was to review the risk of malignancy in branch duct IPMNs in a large single center cohort. Methods: A review of 482 patients with branch duct (BD) IPMN diagnosed between 1995 and 2012 was performed. Patients who underwent primary resection with histopathological confirmation of BD-IPMN, as well as patients being followed with BD-IPMN 1.5 cm for a minimum of one year were included. Results: 331 patients met the above criteria ; 182 (55%) patients underwent primary resection and 149 (45%) were followed (median 42 months, and 61 (41%) for >5 years). Of patients who were primarily followed, 22 (14.8%) underwent surgery because of concerning findings or symptoms (median time to surgery: 21 months, 7-126 m), and only 2 (9% of resected and 1.3% of the cohort) were malignant. Pathology of all the resected cases showed BD-IPMN adenoma in 45% (91/204), borderline tumor in 35% , carcinoma in situ in 10% and invasive cancer in 10% (20/204). Concomitant pancreatic ductal adenocarcinoma (PDAC) (i.e distant from the IPMN) was found in 8 patients (2.4%), all of which were resected. One of these patients had been followed 10 years for a presumed branch duct IPMN. Conclusion: Risk of malignancy in resected IPMN is around 20%, and the risk of concomitant PDAC low (2.4%). Expectant management of patients who do not meet criteria for resection is safe, although the high frequency of borderline tumors (35%) in resected patients and the relatively short median follow-up (42 months) preclude definitive conclusions on the long-term safety of this approach.
P207. Radiologic assessment of pancreatic disease (RAPiD) study: Association of quantitative MRI features with pancreas secretory function in suspected chronic pancreatitis N.I. Sainani, P.A. Banks, L.S. Lee, V. Kadiyala, S.L. Suleiman, D.L. Conwell. Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, MA, USA