1. Management of cystic lesions of the pancreas Marc Barthet, Hôpital Nord, Marseille, France Roma, 11-12 March 2011

5. C.R. Ferrone, W. Brugge, Arch Surg 2009 SCA : 13%; MCA : 18%; IPMN : branch duct 23%; main duct 25%; SPT 5% Endocrine 4% Others 10%

7. Risk of malignancy Serous cystadenoma Branch duct IPMN Mucinous cystadenoma Solid pseudo papillary neoplasm Main duct IPMN 0% 5-15% >30% >50% Singh Pancreas 2007; Barthet Endoscopy 2007

9. Oh et al Am J Gastro 2008

10. Oh et al Am J Gastro 2008 CT: accuracy 54-93 %

11. Oh et al Am J Gastro 2008 EUS without FNA : accuracy 40-93%

12. Oh et al Am J Gastro 2008 CEA : < 4 = SCA CEA : > 300/400 = MCA

13. Criteria at EUS vs. final diagnosis (n=67) Frossard, Amouyal, Amouyal, Palazzo et al Am J Gastroenterol 2003;98:1516 Performance of EUS : morphology alone Diagnosis N Se. Sp. PPV NPV Pseudocyst 6 100 100 100 100 Serous cystadenoma 14 43 76 32 83 Mucinous cystadenoma 17 65 84 58 87 IPMN 14 100 100 100 100 Cystic neuroendocrine T. 6 33 100 100 93 Cystadenocarcinoma 9 88 96 80 93 Pseudosolid & papillary 1 100 100 100 100

16. Cytology Frossard Am J Gastroenterol 2003;98:1516 SC MC Van der Vaaij. Gastrointest Endosc 2005 Diagnostic yield <30%

17. Van der Vaaij. Gastrointest Endosc 2005 * CEA > 400 ng/mL MC/MCA se 57% sp 99% * CEA < 5 ng/mL Serous cystadenoma se 92% sp 87% CEA * Beaujon

18. Van der Vaaij. Gastrointest Endosc 2005 CA 19.9 Beaujon >50 000 U/mL MC/MCA se 72% sp 84%

20. Brugge WR. Gastroenterology 2004 Summary 50% 80% Cytology Imaging EUS Liquid (CEA) 90%

21. Fernandez del Castillo Gastroenterology 2010 IPMN : the main problem ?

22. Actual risk of malignancy according to the location : main duct / side branches Mois Main pancreatic duct Side branches 63 % 15 % 0 20 40 60 80 100 0 20 40 60 Levy P et al Clin Gastroenterol Hepatol 2006; 4:460-8 IPMN : actual risk of malignancy Surgery follow-up (guidelines)

23. Is IPMN malignant ? Predictive factors Sugiyama et al, Br J Surg, 2003; Pais Clin Gastroenterol Hepatol 2007; 5: 489-95; Okabayashi T J Gastroenterol Hepatol 2006;21:462-7 Multivariate analysis, 62 patients operated Mural nodule (RR = 17) diameter Wirsung duct ≥ 7 mm (RR = 5) Multivariate analysis 23 patients diameter wirsung > 10 mm location main duct cyst > 30 mm mural nodule >5 mm Multivariate analysis 74 patients (EUS FNA) age, jaundice, weight loss solid lesion, ductal defect, increased wall thickness Risks : Main duct Wirsung > 7-10mm cyst > 30 mm ? Mural nodule >5 mm

25. Malignancy and IPMN : Sendai Consensus guidelines Tanaka M Pancreatology 2006;6:17-32 Branch duct (BD)-IPMN : surgical resection BD-IPMN <3 cm if worrisome features : cyst-related symptoms dilated MPD > 6 mm mural nodule BD-IPMN > 3 cm irrespective of symptoms

27. Summarizing validation of BD-IPMN surveillance… Rautou Clin Gastro Hepatol2008;6:807-14; Salvia Gut 2007;56:1086-90 Tanaka M Pancreatology 2006;6:17-32; Bishop Clin Gastro Hepatol 2008;6:724-25 Over estimation of the risk of malignancy Estimated rate for development and progression 5-10 % High-risk cysts have to better defined Surveillance intervals can probably be increased

28. No increase in size 91 patients Cyst wall thickening n=3 Surgery in 10 % of patients, no invasive cancer Resection n = 2 Adenoma : n=1 Borderline : n=1 Increase in size 30 patients Suggestive of malignancy n=9 Resection n = 6 In situ carcinoma : n=4 Borderline : n=2 No signs of malignancy n=21 Resection (symptoms) n = 4 Adenoma : n=3 Borderline : n=1 Rautou PA, Levy P, Hammel P, Palazzo L, O’Toole D. Clin Gastroenterol Hepatol 2008 Evolution of branch-duct IPMN under observation 121 patients median follow-up: 3 years

29. Another problem during the follow-up Fernandez del Castillo Gastroenterology 2010; Ingkakul T Ann Surg 2010; 251:70-5; Uehara D Gut 2008; 51:1561-5 Occurrence of ductal adenocarcinoma irrespective of the BD- IPMN Frequency 1 %/year (11% of concomitant case-series) Due to associated PanIN ? Total pancreatectomy

36. IPMN: intra-cystic markers Distinguishing benign from malignant IPMN, n=41 Maire, Palazzo, O’Toole. Am J Gastroenterol 2008 Cyst fluid CEA of > 200 ng/ml CA 72.4 > 40 U/mL Sensitivity, % 90 88 Specificity, % 71 73 PPV, % 50 47 NPV, % 96 96

40. EUS-FNA Histological analysis Tumor markers Monolayer preparation Amylase, CEA , CA 19-9

41. Intracystic markers . Amylase, lipase : ductal communication (IPMN) . ACE : the best < 5 ng/mL : serous cystadenoma > 400 ng/mL : mucinous lesion . Ca 19-9 : mucinous cystadenoma, malignant progression > 50000 U/ml MCA vs others 15% sens; 81 % spec MCA with carcinoma: 86% sens; 85% spec . Ca 72.4 : mucinous cystadenoma, malignant progression . Mucines M1 : disappointing, Ki-ras : disappointing Frossard Am J Gastroenterol 2003;Hammel GCB 2002; Van der Vaaij GIE 2005; Tada Clin Gastro 2006 Amylase, ACE CA19-9 low = SCA ACE > 400 ng/ml = mucinous (K++)

44. Typical features Dilated main pancreatic duct And/or Branched cystic lesion

45. IPMN different types Branch duct type Malignancy 5-15% Combined type Malignancy >50% Main duct type Malignancy >50%

46. EUS-FNAB for patients with IPMN ? Maire, O’Toole, Palazzo Gastrointest Endosc 2003:701-6. Cytology – diagnosis of IMPN (n=18) Histology - IPMN (n=24) Side branch without nodule IPMN with nodule and mass

51. Summarizing validation of BD-IPMN surveillance… Rautou Clin Gastro Hepatol2008;6:807-14; Salvia Gut 2007;56:1086-90 Tanaka M Pancreatology 2006;6:17-32; Bishop Clin Gastro Hepatol 2008;6:724-25 Over estimation of the risk of malignancy Estimated rate for development and progression 5-10 % High-risk cyts have to better defined Surveillance intervals can probably be increased