Korean J Gastroenterol.  2024 May;83(5):208-215. 10.4166/kjg.2024.036.

International Evidence-based Kyoto Guidelines for the Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas

• Shin DW

• KMID: 2555975
• DOI: http://doi.org/10.4166/kjg.2024.036

Figure

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  Fig. 1 Morphological findings of IPMN. (A) Gastric type with low grade dysplasia. (B) Intestinal type with high grade dysplasia. (C) Pancreatobiliary type with high grade dysplasia (x20, Hematoxylin and eosin staining).

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  Fig. 2 Algorithm for the management of suspected BD-IPMN.

Reference

1. Tanaka M, Chari S, Adsay V, et al. 2006; International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 6:17–32. DOI: 10.1159/000090023. PMID: 16327281.

2. Tanaka M, Fernández-del Castillo C, Adsay V, et al. 2012; International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 12:183–197. DOI: 10.1016/j.pan.2012.04.004. PMID: 22687371.

3. Tanaka M, Fernández-Del Castillo C, Kamisawa T, et al. 2017; Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 17:738–753. DOI: 10.1016/j.pan.2017.07.007. PMID: 28735806.

4. Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, et al. 2024; International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology. 24:255–270. DOI: 10.1016/j.pan.2023.12.009. PMID: 38182527.

5. Ohno E, Balduzzi A, Hijioka S, et al. 2024; Association of high-risk stigmata and worrisome features with advanced neoplasia in intraductal papillary mucinous neoplasms (IPMN): A systematic review. Pancreatology. 24:48–61. DOI: 10.1016/j.pan.2023.12.002. PMID: 38161091.

6. Kazmi SZ, Jung HS, Han Y, et al. 2024; Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas. Pancreatology. 24:463–488. DOI: 10.1016/j.pan.2024.02.015. PMID: 38480047.

7. Wood LD, Adsay NV, Basturk O, et al. 2023; Systematic review of challenging issues in pathology of intraductal papillary mucinous neoplasms. Pancreatology. 23:878–891. DOI: 10.1016/j.pan.2023.08.002. PMID: 37604731.

8. Pflüger MJ, Jamouss KT, Afghani E, et al. 2023; Predictive ability of pancreatic cyst fluid biomarkers: A systematic review and metaanalysis. Pancreatology. 23:868–877. DOI: 10.1016/j.pan.2023.05.005. PMID: 37230894.

9. Adsay V, Mino-Kenudson M, Furukawa T, et al. 2016; Pathologic evaluation and reporting of intraductal papillary mucinous neoplasms of the pancreas and other tumoral intraepithelial neoplasms of pancreatobiliary tract: Recommendations of verona consensus meeting. Ann Surg. 263:162–177. DOI: 10.1097/SLA.0000000000001173. PMID: 25775066. PMCID: PMC4568174.

10. Hruban RH, Takaori K, Klimstra DS, et al. 2004; An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 28:977–987. DOI: 10.1097/01.pas.0000126675.59108.80. PMID: 15252303.

11. Furukawa T, Klöppel G, Volkan Adsay N, et al. 2005; Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 447:794–799. DOI: 10.1007/s00428-005-0039-7. PMID: 16088402.

12. Correa-Gallego C, Miyasaka Y, Hozaka Y, et al. 2023; Surveillance after resection of non-invasive intraductal papillary mucinous neoplasms (IPMN). A systematic review. Pancreatology. 23:258–265. DOI: 10.1016/j.pan.2023.02.008. PMID: 36906508.

13. Lekkerkerker SJ, Besselink MG, Busch OR, et al. 2017; Comparing 3 guidelines on the management of surgically removed pancreatic cysts with regard to pathological outcome. Gastrointest Endosc. 85:1025–1031. DOI: 10.1016/j.gie.2016.09.027. PMID: 27693645.

14. Tacelli M, Celsa C, Magro B, et al. 2020; Diagnostic performance of endoscopic ultrasound through-the-needle microforceps biopsy of pancreatic cystic lesions: Systematic review with meta-analysis. Dig Endosc. 32:1018–1030. DOI: 10.1111/den.13626. PMID: 31912580.

15. Facciorusso A, Crinò SF, Gkolfakis P, et al. 2022; Needle tract seeding after endoscopic ultrasound tissue acquisition of pancreatic lesions: A systematic review and meta-analysis. Diagnostics (Basel). 12:2113. DOI: 10.3390/diagnostics12092113. PMID: 36140514. PMCID: PMC9498098.

16. Ohtsuka T, Matsunaga T, Kimura H, et al. 2014; Role of pancreatic juice cytology in the preoperative management of intraductal papillary mucinous neoplasm of the pancreas in the era of international consensus guidelines 2012. World J Surg. 38:2994–3001. DOI: 10.1007/s00268-014-2684-y. PMID: 25037612.

17. Yamakawa K, Masuda A, Nakagawa T, et al. 2019; Evaluation of efficacy of pancreatic juice cytology for risk classification according to international consensus guidelines in patients with intraductal papillary mucinous neoplasm; a retrospective study. Pancreatology. 19:424–428. DOI: 10.1016/j.pan.2019.02.013. PMID: 30857854.

18. Srinivasan N, Koh YX, Goh BKP. 2019; Systematic review of the utility of 18-FDG PET in the preoperative evaluation of IPMNs and cystic lesions of the pancreas. Surgery. 165:929–937. DOI: 10.1016/j.surg.2018.11.006. PMID: 30577952.

19. Serafini S, Sperti C, Brazzale AR, et al. 2020; The role of positron emission tomography in clinical management of intraductal papillary mucinous neoplasms of the pancreas. Cancers (Basel). 12:807. DOI: 10.3390/cancers12040807. PMID: 32230809. PMCID: PMC7226258.

20. Hozaka Y, Kurahara H, Oi H, et al. 2021; Clinical utility and limitation of diagnostic ability for different degrees of dysplasia of intraductal papillary mucinous neoplasms of the pancreas using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography. Cancers (Basel). 13:4633. DOI: 10.3390/cancers13184633. PMID: 34572860. PMCID: PMC8465733.

21. Hwang JA, Choi SY, Lee JE, et al. 2020; Pre-operative nomogram predicting malignant potential in the patients with intraductal papillary mucinous neoplasm of the pancreas: focused on imaging features based on revised international guideline. Eur Radiol. 30:3711–3722. DOI: 10.1007/s00330-020-06736-6. PMID: 32095876.

22. Fang X, Liu F, Li J, et al. 2021; Computed tomography nomogram to predict a high-risk intraductal papillary mucinous neoplasm of the pancreas. Abdom Radiol (NY). 46:5218–5228. DOI: 10.1007/s00261-021-03247-w. PMID: 34409514.

23. Shimizu Y, Hijioka S, Hirono S, et al. 2020; New model for predicting malignancy in patients with intraductal papillary mucinous neoplasm. Ann Surg. 272:155–162. DOI: 10.1097/SLA.0000000000003108. PMID: 30499803.

24. European Study Group on Cystic Tumours of the Pancreas. 2018; European evidence-based guidelines on pancreatic cystic neoplasms. Gut. 67:789–804. DOI: 10.1136/gutjnl-2018-316027. PMID: 29574408. PMCID: PMC5890653.

25. Gemenetzis G, Bagante F, Griffin JF, et al. 2017; Neutrophil-to-lymphocyte ratio is a predictive marker for invasive malignancy in intraductal papillary mucinous neoplasms of the pancreas. Ann Surg. 266:339–345. DOI: 10.1097/SLA.0000000000001988. PMID: 27631774.

26. Jang JY, Park T, Lee S, et al. 2017; Proposed nomogram predicting the individual risk of malignancy in the patients with branch duct type intraductal papillary mucinous neoplasms of the pancreas. Ann Surg. 266:1062–1068. DOI: 10.1097/SLA.0000000000001985. PMID: 27607098.

27. Attiyeh MA, Fernández-Del Castillo C, Al Efishat M, et al. 2018; Development and validation of a multi-institutional preoperative nomogram for predicting grade of dysplasia in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas: A report from the pancreatic surgery consortium. Ann Surg. 267:157–163. DOI: 10.1097/SLA.0000000000002015. PMID: 28079542. PMCID: PMC5565720.

28. Kim JR, Jang JY, Kang MJ, et al. 2015; Clinical implication of serum carcinoembryonic antigen and carbohydrate antigen 19-9 for the prediction of malignancy in intraductal papillary mucinous neoplasm of pancreas. J Hepatobiliary Pancreat Sci. 22:699–707. DOI: 10.1002/jhbp.275. PMID: 26178866.

29. Wang W, Zhang L, Chen L, et al. 2015; Serum carcinoembryonic antigen and carbohydrate antigen 19-9 for prediction of malignancy and invasiveness in intraductal papillary mucinous neoplasms of the pancreas: A meta-analysis. Biomed Rep. 3:43–50. DOI: 10.3892/br.2014.376. PMID: 25469245. PMCID: PMC4251113.

30. Jang DK, Ryu JK, Chung KH, et al. 2016; Risk factors for progression or malignancy in main-duct and mixed-type intraductal papillary mucinous neoplasm of the pancreas. Pancreas. 45:1027–1031. DOI: 10.1097/MPA.0000000000000592. PMID: 26692447.

31. Morales-Oyarvide V, Mino-Kenudson M, Ferrone CR, et al. 2017; Diabetes mellitus in intraductal papillary mucinous neoplasm of the pancreas is associated with high-grade dysplasia and invasive carcinoma. Pancreatology. 17:920–926. DOI: 10.1016/j.pan.2017.08.073. PMID: 28890154.

32. Duconseil P, Adham M, Sauvanet A, et al. 2018; Fukuoka-negative branch-duct IPMNs: When to worry? A Study from the French Surgical Association (AFC). Ann Surg Oncol. 25:1017–1025. DOI: 10.1245/s10434-017-6318-0. PMID: 29392508.

33. Gausman V, Kandel P, Van Riet PA, et al. 2018; Predictors of progression among low-risk intraductal papillary mucinous neoplasms in a multicenter surveillance cohort. Pancreas. 47:471–476. DOI: 10.1097/MPA.0000000000001027. PMID: 29521942.

34. Iwaya H, Hijioka S, Mizuno N, et al. 2019; Usefulness of septal thickness measurement on endoscopic ultrasound as a predictor of malignancy of branched-duct and mixed-type intraductal papillary mucinous neoplasm of the pancreas. Dig Endosc. 31:672–681. DOI: 10.1111/den.13408. PMID: 30920028.

35. Chai L, Zhu N, Wang Q, Wang T, Chai W. 2021; Assessment of malignancy potential in intraductal papillary mucinous neoplasms of the pancreas on MDCT. Acad Radiol. 28:679–686. DOI: 10.1016/j.acra.2020.03.042. PMID: 32591278.

36. Seo N, Byun JH, Kim JH, et al. 2016; Validation of the 2012 International consensus guidelines using computed tomography and magnetic resonance imaging: Branch duct and main duct intraductal papillary mucinous neoplasms of the pancreas. Ann Surg. 263:557–564. DOI: 10.1097/SLA.0000000000001217. PMID: 25822687.

37. Kwong WT, Lawson RD, Hunt G, et al. 2015; Rapid growth rates of suspected pancreatic cyst branch duct intraductal papillary mucinous neoplasms predict malignancy. Dig Dis Sci. 60:2800–2806. DOI: 10.1007/s10620-015-3679-8. PMID: 25924899.

38. Akahoshi K, Ono H, Akasu M, et al. 2018; Rapid growth speed of cysts can predict malignant intraductal mucinous papillary neoplasms. J Surg Res. 231:195–200. DOI: 10.1016/j.jss.2018.05.056. PMID: 30278929.

39. Kolb JM, Argiriadi P, Lee K, et al. 2018; Higher Growth rate of branch duct intraductal papillary mucinous neoplasms associates with worrisome features. Clin Gastroenterol Hepatol. 16:1481–1487. DOI: 10.1016/j.cgh.2018.02.050. PMID: 29535058.

40. Ohtsuka T, Kono H, Nagayoshi Y, et al. 2012; An increase in the number of predictive factors augments the likelihood of malignancy in branch duct intraductal papillary mucinous neoplasm of the pancreas. Surgery. 151:76–83. DOI: 10.1016/j.surg.2011.07.009. PMID: 21875733.

41. Zelga P, Hernandez-Barco YG, Qadan M, et al. 2022; Number of worrisome features and risk of malignancy in intraductal papillary mucinous neoplasm. J Am Coll Surg. 234:1021–1030. DOI: 10.1097/XCS.0000000000000176. PMID: 35703792.

42. Berger AW, Schwerdel D, Costa IG, et al. 2016; Detection of hot-spot mutations in circulating cell-free dna from patients with intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology. 151:267–270. DOI: 10.1053/j.gastro.2016.04.034. PMID: 27343369.

43. Hata T, Mizuma M, Motoi F, et al. 2020; GNAS mutation detection in circulating cell-free DNA is a specific predictor for intraductal papillary mucinous neoplasms of the pancreas, especially for intestinal subtype. Sci Rep. 10:17761. DOI: 10.1038/s41598-020-74868-2. PMID: 33082481. PMCID: PMC7576136.

44. Singhi AD, Nikiforova MN, Fasanella KE, et al. 2014; Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. Clin Cancer Res. 20:4381–4389. DOI: 10.1158/1078-0432.CCR-14-0513. PMID: 24938521.

45. Springer S, Wang Y, Dal Molin M, et al. 2015; A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology. 149:1501–1510. DOI: 10.1053/j.gastro.2015.07.041. PMID: 26253305. PMCID: PMC4782782.

46. Singhi AD, McGrath K, Brand RE, et al. 2018; Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut. 67:2131–2141. DOI: 10.1136/gutjnl-2016-313586. PMID: 28970292. PMCID: PMC6241612.

47. Springer S, Masica DL, Dal Molin M, et al. 2019; A multimodality test to guide the management of patients with a pancreatic cyst. Sci Transl Med. 11:eaav4772. DOI: 10.1126/scitranslmed.aav4772. PMID: 31316009. PMCID: PMC7859881.

48. Raut CP, Cleary KR, Staerkel GA, et al. 2006; Intraductal papillary mucinous neoplasms of the pancreas: effect of invasion and pancreatic margin status on recurrence and survival. Ann Surg Oncol. 13:582–594. DOI: 10.1245/ASO.2006.05.002. PMID: 16523362.

49. Kim HS, Han Y, Kang JS, et al. 2022; Fate of patients with intraductal papillary mucinous neoplasms of pancreas after resection according to the pathology and margin status: Continuously increasing risk of recurrence even after curative resection suggesting necessity of lifetime surveillance. Ann Surg. 276:e231–e238. DOI: 10.1097/SLA.0000000000004478. PMID: 32941274.

50. Chi Z, Dhall D, Mertens R. 2022; The use of intraoperative frozen sections in guiding the extent of pancreatic resections for intraductal papillary mucinous neoplasms: A single institution experience and review of the literature. Pancreas. 51:63–74. DOI: 10.1097/MPA.0000000000001963. PMID: 35195597.

51. Bhardwaj N, Dennison AR, Maddern GJ, Garcea G. 2016; Management implications of resection margin histology in patients undergoing resection for IPMN: A meta-analysis. Pancreatology. 16:309–317. DOI: 10.1016/j.pan.2016.02.008. PMID: 26987800.

52. Adsay NV, Pierson C, Sarkar F, et al. 2001; Colloid (mucinous noncystic) carcinoma of the pancreas. Am J Surg Pathol. 25:26–42. DOI: 10.1097/00000478-200101000-00003. PMID: 11145249.

53. Nara S, Shimada K, Sakamoto Y, Esaki M, Kosuge T, Hiraoka N. 2009; Clinical significance of frozen section analysis during resection of intraductal papillary mucinous neoplasm: should a positive pancreatic margin for adenoma or borderline lesion be resected additionally? J Am Coll Surg. 209:614–621. DOI: 10.1016/j.jamcollsurg.2009.07.023. PMID: 19854402.

54. Ciprani D, Weniger M, Qadan M, et al. 2020; Risk of malignancy in small pancreatic cysts decreases over time. Pancreatology. 20:1213–1217. DOI: 10.1016/j.pan.2020.08.003. PMID: 32819844. PMCID: PMC8168401.

55. Oyama H, Tada M, Takagi K, et al. 2020; Long-term risk of malignancy in branch-duct intraductal papillary mucinous neoplasms. Gastroenterology. 158:226–237.e5. DOI: 10.1053/j.gastro.2019.08.032. PMID: 31473224.

56. Han Y, Kwon W, Lee M, et al. 2024; Optimal surveillance interval of branch duct intraductal papillary mucinous neoplasm of the pancreas. JAMA Surg. 159:389–396. DOI: 10.1001/jamasurg.2023.7010. PMID: 38231494.

57. Marchegiani G, Pollini T, Burelli A, et al. 2023; Surveillance for presumed BD-IPMN of the pancreas: Stability, size, and age identify targets for discontinuation. Gastroenterology. 165:1016–1024.e5. DOI: 10.1053/j.gastro.2023.06.022. PMID: 37406887.

58. Miller JR, Meyer JE, Waters JA, et al. 2011; Outcome of the pancreatic remnant following segmental pancreatectomy for non-invasive intraductal papillary mucinous neoplasm. HPB (Oxford). 13:759–766. DOI: 10.1111/j.1477-2574.2011.00354.x. PMID: 21999588. PMCID: PMC3238009.

59. He J, Cameron JL, Ahuja N, et al. 2013; Is it necessary to follow patients after resection of a benign pancreatic intraductal papillary mucinous neoplasm? J Am Coll Surg. 216:657–665. discussion 665–667. DOI: 10.1016/j.jamcollsurg.2012.12.026. PMID: 23395158. PMCID: PMC3963007.

60. Pflüger MJ, Griffin JF, Hackeng WM, et al. 2022; The impact of clinical and pathological features on intraductal papillary mucinous neoplasm recurrence after surgical resection: Long-term follow-up analysis. Ann Surg. 275:1165–1174. DOI: 10.1097/SLA.0000000000004427. PMID: 33214420. PMCID: PMC9516436.

61. Amini N, Habib JR, Blair A, et al. 2022; Invasive and noninvasive progression after resection of noninvasive intraductal papillary mucinous neoplasms. Ann Surg. 276:370–377. DOI: 10.1097/SLA.0000000000004488. PMID: 33201121. PMCID: PMC9844542.

62. Pea A, Yu J, Rezaee N, et al. 2017; Targeted DNA sequencing reveals patterns of local progression in the pancreatic remnant following resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg. 266:133–141. DOI: 10.1097/SLA.0000000000001817. PMID: 27433916. PMCID: PMC5243861.

63. Rezaee N, Barbon C, Zaki A, et al. 2016; Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia is a risk factor for the subsequent development of pancreatic ductal adenocarcinoma. HPB (Oxford). 18:236–246. DOI: 10.1016/j.hpb.2015.10.010. PMID: 27017163. PMCID: PMC4814593.

64. Majumder S, Philip NA, Singh Nagpal SJ, et al. 2019; High-grade dysplasia in resected main-duct intraductal papillary mucinous neoplasm (MD-IPMN) is associated with an increased risk of subsequent pancreatic cancer. Am J Gastroenterol. 114:524–529. DOI: 10.1038/s41395-018-0403-2. PMID: 30413822.

65. Landa J, Allen P, D'Angelica M, Schwartz LH. 2009; Recurrence patterns of intraductal papillary mucinous neoplasms of the pancreas on enhanced computed tomography. J Comput Assist Tomogr. 33:838–843. DOI: 10.1097/RCT.0b013e3181a7e2a8. PMID: 19940647.

66. Marchegiani G, Mino-Kenudson M, Sahora K, et al. 2015; IPMN involving the main pancreatic duct: biology, epidemiology, and long-term outcomes following resection. Ann Surg. 261:976–983. DOI: 10.1097/SLA.0000000000000813. PMID: 24979607. PMCID: PMC5614498.

67. Lee KS, Sekhar A, Rofsky NM, Pedrosa I. 2010; Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol. 105:2079–2084. DOI: 10.1038/ajg.2010.122. PMID: 20354507.

68. de Jong K, Nio CY, Hermans JJ, et al. 2010; High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol. 8:806–811. DOI: 10.1016/j.cgh.2010.05.017. PMID: 20621679.

69. Ip IK, Mortele KJ, Prevedello LM, Khorasani R. 2011; Focal cystic pancreatic lesions: assessing variation in radiologists' management recommendations. Radiology. 259:136–141. DOI: 10.1148/radiol.10100970. PMID: 21292867.

70. Girometti R, Intini S, Brondani G, et al. 2011; Incidental pancreatic cysts on 3D turbo spin echo magnetic resonance cholangiopancreatography: prevalence and relation with clinical and imaging features. Abdom Imaging. 36:196–205. DOI: 10.1007/s00261-010-9618-4. PMID: 20473669.

71. Kromrey ML, Bülow R, Hübner J, et al. 2018; Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut. 67:138–145. DOI: 10.1136/gutjnl-2016-313127. PMID: 28877981.

72. Elta GH, Enestvedt BK, Sauer BG, Lennon AM. 2018; ACG clinical guideline: diagnosis and management of pancreatic cysts. Am J Gastroenterol. 113:464–479. DOI: 10.1038/ajg.2018.14. PMID: 29485131.