Outline. Intraductal Papillary Mucinous Neoplasm (IPMN) Guideline Review 4/6/2017. Case Example Background Classification Histology Guidelines
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1 Intraductal Papillary Mucinous Neoplasm (IPMN) Guideline Review The Nurse Practitioner Association New York State Capital Region Teaching Day Matthew Warndorf MD Case Example Background Classification Histology Guidelines Outline Case Example A 67 yo F presents to the ER with left flank pain concerning for nephrolithiasis. A non contrast CT A&P is performed, which reveals a 5 mm non obstructing stone in the left ureter as well as a 1.5 cm low attenuation lesion, concerning for possible mass in the pancreatic body. 1
2 Case Example She follows up with her PCP and a contrast enhanced CT is obtained which describes a 1.6 cm, fluid density, cystic lesion in the body of the pancreas. MRCP is recommended for further characterization. Case Example MRCP is obtained and describes a 1.3 x 1.6 cm cystic lesion in the body of the pancreas, as well as several other small (<5mm) cystic lesions in the head and body of the pancreas, and a non dilated main pancreatic duct, suggestive of multifocal side branch IPMN or sequelae of pancreatitis. Case Example Referred to GI for further evaluation and management recommendations. No past history of pancreatitis. No family history of pancreatic cancer. Denies: abdominal pain, back pain, unintentional weight loss, and new or worsening diabetes. Discuss MRCP in 1 year for surveillance, but due to anxiety associated with findings proceed with endoscopic ultrasound. 2
3 Case Example EUS shows 1.5 cm anechoic lesion, consistent with cyst, thin wall, no associated nodularity, or mass lesion, and a nondilated pancreatic duct. There are also a few similar appearing, but smaller cysts in head and body. Fluid aspiration performed and shows elevated CEA level consistent with a mucinous neoplasm. Diagnosis: side branch IPMN Recommend surveillance MRCP in 1 year. IPMN Background Mucin producing neoplastic cystic lesion Initially described in the early 1980s Identified with increasing frequency with increased use of cross sectional imaging Pre malignant but natural history of progression to cancer not well characterized Presenting Symptoms Asymptomatic Incidentally found on imaging performed for a different indication Abdominal pain Back pain Acute pancreatitis Jaundice New or worsening diabetes 3
4 Classification Main duct Branch duct Mixed type Classification Main Duct IPMN Segmental or diffuse dilation of main PD > 5 mm without other cause of obstruction Classification Branch Duct IPMN Pancreatic cyst > 5 mm that communicate with main pancreatic duct 4
5 Classification Mixed Type IPMN Meet criteria for both MD and BD Histology Characterized by intraductal dysplastic epithelium with papillae containing goblet cells and extensive mucin production Histologic subclassification Gastric Intestinal Pancreatobiliary Oncocytic Ohtsuka T et al, Pancreapedia 2012 Histology Gastric Intestinal Pancreatobiliary Oncocytic Ohtsuka T et al,
6 Histology Gastric: Mostly seen in branch duct IPMN, typically low grade Intestinal: Mostly seen in main duct IPMN Pancreatobiliary: Least well characterized; least common Oncocytic: Tend to be large; relatively uncommon and limited invasion Ohtsuka T et al, Pancreapedia 2012 IPMN and Malignancy Pre malignant Significant differences between main duct and branch duct Early data from surgical series over represents malignant IPMN Symptomatic and/or larger lesions Pre Malignant Potential: Surgical Series Main Duct: Mean frequency malignancy: 62% Mixed Type: Mean frequency malignancy: 58% Branch Duct: Mean frequency malignancy: 26% 6
7 Pre Malignant Potential Olmstead County and Surveillance, Epidemiology, and End Results 9 (SEER 9) database The increased diagnosis of IPMN does not translate into clinically relevant disease Pre malignant Potential Annual malignancy rate of BD IPMN 2 3% [Cyst] seen incidentally on MRI has a 10 in 100,000 chance of being a mucinous invasive malignancy and 17 in 100,000 chance of being a ductal cancer Uncharacterized pancreatic cysts: Rate of developing malignancy 0.24% per year Vege S et al, Gastroenterology 2015 Guidelines Sendai Guidelines (2006) Fukuoka Guidelines (2012) AGA Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts (2015) 7
8 Sendai Japan guide.com Sendai Guidelines (2006) 11 th Congress of the International Association of Pancreatology in 2004 International consensus guidelines for management of IPMN (and MCN) Important initial recommendations for resection and surveillance of IPMN Fukuoka Japan 8
9 Fukuoka Guidelines (2012) 14 th Congress of the International Association of Pancreatology in 2010 Define high risk and worrisome features Fukuoka Guidelines (2012) High risk stigmata Obstructive jaundice Enhancing solid component within cyst Main duct >10 mm If high risk stigmata present consider surgery Fukuoka Guidelines (2012) Worrisome features Pancreatitis Cyst >3 cm Thickened/enhancing cyst wall Main duct size 5 9 mm Non enhancing mural nodule Abrupt change in caliber of pancreatic duct with distal pancreatic atrophy If worrisome feature present perform EUS If EUS demonstrates mural nodule, main duct involvement, or cytology suspicious or positive for malignancy Consider surgery 9
10 Fukuoka Guidelines (2012) Surveillance of Branch Duct IPMN Less than 1 cm: MRCP 2 3 years 1 2 cm: MRCP yearly x 2 years; lengthen interval if no change 2 3 cm: EUS in 3 6 months; lengthen interval alternating MRCP with EUS Consider surgery in young fit patients with need for prolonged surveillance Greater than 3 cm: alternating MRCP and EUS every 3 6 months Strongly consider surgery in young fit patients Bethesda AGA Guidelines (2015) AGA Guidelines (2015) Asymptomatic neoplastic pancreatic cysts Not just IPMN Main duct IPMN not included 10
11 AGA Guidelines (2015) Low Risk Features No main duct involvement Less than 3 cm No solid component High Risk Features Dilated main duct Greater than 3 cm Presence of a solid component Vege S et al, Gastroenterology 2015 Scheiman J et al, Gastroenterology 2015 AGA Guidelines (2015) Surveillance for Low Risk MRCP in 1 year and then every 2 years for a total of 5 years if no change in size or characteristics MRCP is preferred over CT and EUS for surveillance Structural relationship between PD and cyst No radiation Less invasive than EUS Vege S et al, Gastroenterology 2015 Scheiman J et al, Gastroenterology 2015 AGA Guidelines (2015) When to refer for EUS At least 2 high risk features Size >3 cm Dilated main pancreatic duct Presence of solid component Changes in low risk lesion during surveillance Vege S et al, Gastroenterology 2015 Scheiman J et al, Gastroenterology
12 Endoscopic Ultrasound (EUS) Assess for high risk or worrisome features Cytology CEA Fluid consistency Molecular analysis When to Discontinue Surveillance If no significant change in characteristics of cyst after 5 years of surveillance If patient no longer a surgical candidate Vege S et al, Gastroenterology 2015 Scheiman J et al, Gastroenterology 2015 Surgical Resection Refer to high volume pancreatic center Pancreaticoduodenectomy Distal pancreatectomy Total pancreatectomy 12
13 Summary IPMN are pre malignant cystic lesions arising from pancreatic duct epithelium Most are incidentally found Cause considerable anxiety Branch duct and main duct types do NOT have same risk for malignant transformation Guidelines are helpful but not perfect Thank You References Gardner T, Glass L, Smith K, et al. Pancreatic Cyst Prevalence and the Risk of Mucin Producing Adenocarcinoma in US Adults. American Journal of Gastroenterology 2013; 108: Klibansky D, Reid Lombardo K, Gordon S, et al. The Clinical Relevance of the Increasing Incidence of Intraductal Papillary Mucinous Neoplasm. Clinical Gastroenterology and Hepatology 2012;10: Ohtsuka T, Tanaka M. Intraductal Papillary Mucinous Neoplasm of the Pancreas; Characteristics, Diagnosis, and Management Based on the Fukuoka Consensus Guidelines Pancreapedia 2014;1:1 10. Scheiman J, Hwang J, Moayyedi P. American Gastroenterological Association Technical Review on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts. Gastroenterology 2015;148: Tanaka M, Chari S, Adsay V, et al. International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas. Pancreatology 2006;6: Tanaka M, Fernandez del Castillo C, Adsay V, et al. International Consensus Guidelines 2012 for the Management of IPMN and MCN of the Pancreas. Pancreatology 2012;12(3): Vege S, Ziring B, Jain R, et al. American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts. Gastroenterology 2015;148:
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