Intraductal Papillary Mucinous Neoplasm of the Pancreas: An Overview of Surgical Management

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) are commonly identified cystic lesions in the pancreas that may carry malignant potential for pancreatic ductal adenocarcinoma. Risk stratification of identified lesions is critical to determine which patients may benefit from surgical resection. Key high-risk features include size, growth, main pancreatic duct involvement, obstructive jaundice, and enhancing solid components on imaging. The surgical technique of choice depends on IPMN location, with pancreatoduodenectomy being the most common procedure due to the high incidence of high-risk IPMNs in the head of the pancreas. The extent of resection is guided by imaging and/or endoscopic data, potentially including intraoperative frozen section analysis to assess for high-grade dysplasia or invasive IPMN. Postoperative surveillance of the remnant gland is crucial and based on the risk of disease recurrence after the surgery, which is determined by the anatomopathological report.

Keywords

pancreatic cystic neoplasms - pancreatic cancer - intraductal papillary mucinous neoplasm - pancreatic adenocarcinoma - pancreatic surgery

Publication History

Received: 21 October 2024

Accepted: 13 March 2025

Article published online:
28 April 2025

• References

• 1 Zerboni G, Signoretti M, Crippa S, Falconi M, Arcidiacono PG, Capurso G. Systematic review and meta-analysis: prevalence of incidentally detected pancreatic cystic lesions in asymptomatic individuals. Pancreatology 2019; 19 (01) 2-9
• 2 Tanaka M, Fernández-del Castillo C, Adsay V. et al; International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12 (03) 183-197
• 3 Strobel O, Neoptolemos J, Jäger D, Büchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol 2019; 16 (01) 11-26
• 4 Brugge WR. Diagnosis and management of cystic lesions of the pancreas. J Gastrointest Oncol 2015; 6 (04) 375-388
• 5 Malleo G, Marchegiani G, Borin A. et al. Observational study of the incidence of pancreatic and extrapancreatic malignancies during surveillance of patients with branch-duct intraductal papillary mucinous neoplasm. Ann Surg 2015; 261 (05) 984-990
• 6 Kiemen AL, Dequiedt L, Shen Y. et al. PanIN or IPMN? Redefining lesion size in 3 dimensions. Am J Surg Pathol 2024; 48 (07) 839-845
• 7 Lennon AM, Wolfgang CL, Canto MI. et al. The early detection of pancreatic cancer: what will it take to diagnose and treat curable pancreatic neoplasia?. Cancer Res 2014; 74 (13) 3381-3389
• 8 Kleeff J, Korc M, Apte M. et al. Pancreatic cancer. Nat Rev Dis Primers 2016; 2: 16022
• 9 Dong W, Zhen D, Xiaoyan W. et al. The effectiveness of endoscopic ultrasonography findings to distinguish benign and malignant intraductal papillary mucinous neoplasm. Surg Endosc 2023; 37 (06) 4681-4688
• 10 Harima H, Kaino S, Shinoda S, Kawano M, Suenaga S, Sakaida I. Differential diagnosis of benign and malignant branch duct intraductal papillary mucinous neoplasm using contrast-enhanced endoscopic ultrasonography. World J Gastroenterol 2015; 21 (20) 6252-6260
• 11 Kim KW, Park SH, Pyo J. et al. Imaging features to distinguish malignant and benign branch-duct type intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Ann Surg 2014; 259 (01) 72-81
• 12 Sharib JM, Fonseca AL, Swords DS. et al. Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making?. Surgery 2018; 164 (06) 1178-1184
• 13 Crippa S, Pergolini I, Rubini C. et al. Risk of misdiagnosis and overtreatment in patients with main pancreatic duct dilatation and suspected combined/main-duct intraductal papillary mucinous neoplasms. Surgery 2016; 159 (04) 1041-1049
• 14 Paini M, Crippa S, Partelli S. et al. Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas. World J Gastroenterol 2014; 20 (29) 10008-10023
• 15 Iyer MK, Shi C, Eckhoff AM, Fletcher A, Nussbaum DP, Allen PJ. Digital spatial profiling of intraductal papillary mucinous neoplasms: toward a molecular framework for risk stratification. Sci Adv 2023; 9 (11) eade4582
• 16 Rangwani S, Juakiem W, Krishna SG, El-Dika S. Role of endoscopic ultrasound in the evaluation of pancreatic cystic neoplasms: a concise review. Diagnostics (Basel) 2023; 13 (04) 705
• 17 Kang H-J, Lee JM, Joo I. et al. Assessment of malignant potential in intraductal papillary mucinous neoplasms of the pancreas: comparison between multidetector CT and MR imaging with MR cholangiopancreatography. Radiology 2016; 279 (01) 128-139
• 18 Tanaka M, Fernández-Del Castillo C, Kamisawa T. et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 2017; 17 (05) 738-753
• 19 European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018; 67 (05) 789-804
• 20 Efthymiou A, Podas T, Zacharakis E. Endoscopic ultrasound in the diagnosis of pancreatic intraductal papillary mucinous neoplasms. World J Gastroenterol 2014; 20 (24) 7785-7793
• 21 Ohtsuka T, Fernandez-Del Castillo C, Furukawa T. et al. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology 2024; 24 (02) 255-270
• 22 Vege SS, Ziring B, Jain R, Moayyedi P. Clinical Guidelines Committee, American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015; 148 (04) 819-822 , e12–e13
• 23 Puri PM, Watkins AA, Kent TS. et al. Decision-making for the management of cystic lesions of the pancreas: How satisfied are patients with surgery?. J Gastrointest Surg 2018; 22 (01) 88-97
• 24 Salvia R, Burelli A, Perri G, Marchegiani G. State-of-the-art surgical treatment of IPMNs. Langenbecks Arch Surg 2021; 406 (08) 2633-2642
• 25 Pollini T, Andrianello S, Caravati A. et al. The management of intraductal papillary mucinous neoplasms of the pancreas. Minerva Chir 2019; 74 (05) 414-421
• 26 Hashimoto D, Satoi S, Yamamoto T. et al. Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy. Pancreatology 2022; 22 (07) 1046-1053
• 27 Rompen IF, Habib JR, Kinny-Köster B. et al. Total versus partial pancreatectomy in patients with pancreatic cancer arising from multifocal or diffuse intraductal papillary mucinous neoplasia - a multicenter observational study. Ann Surg 2024; . Epub ahead of print
• 28 Poiraud C, El Amrani M, Barbier L. et al. Total pancreatectomy for presumed intraductal papillary mucinous neoplasms: a multicentric study of the French Surgical Association (AFC). Ann Surg 2018; 268 (05) 823-830
• 29 Ratnayake B, Pendharkar SA, Connor S. et al. Patient volume and clinical outcome after pancreatic cancer resection: a contemporary systematic review and meta-analysis. Surgery 2022; 172 (01) 273-283
• 30 Pulvirenti A, Margonis GA, Morales-Oyarvide V. et al. Intraductal papillary mucinous neoplasms: Have IAP consensus guidelines changed our approach?: Results from a multi-institutional study. Ann Surg 2021; 274 (06) e980-e987
• 31 Torphy RJ, Friedman C, Halpern A. et al. Comparing short-term and oncologic outcomes of minimally invasive versus open pancreaticoduodenectomy across low and high volume centers. Ann Surg 2019; 270 (06) 1147-1155
• 32 de Rooij T, van Hilst J, van Santvoort H. et al; Dutch Pancreatic Cancer Group. Minimally invasive versus open distal pancreatectomy (LEOPARD): a multicenter patient-blinded randomized controlled trial. Ann Surg 2019; 269 (01) 2-9
• 33 Zhun Hong Wong N, Wei Ting Yap D, Lei Ng S, Yu Ning Ng J, James JJ, Wei Chieh Kow A. Oncological outcomes in minimally invasive vs. open distal pancreatectomy: a systematic review and network meta-analysis. Front Surg 2024; 11: 1369169
• 34 Podda M, Gerardi C, Di Saverio S. et al. Robotic-assisted versus open pancreaticoduodenectomy for patients with benign and malignant periampullary disease: a systematic review and meta-analysis of short-term outcomes. Surg Endosc 2020; 34 (06) 2390-2409
• 35 Fu Y, Qiu J, Yu Y, Wu D, Zhang T. Meta-analysis of robotic versus open pancreaticoduodenectomy in all patients and pancreatic cancer patients. Front Surg 2022; 9: 989065
• 36 Fong ZV, Lwin TM, Aliaj A, Wang J, Clancy TE. Four-day robotic Whipple: early discharge after robotic pancreatoduodenectomy. J Am Coll Surg 2023; 236 (06) 1172-1179
• 37 Khalid A, Ahmed H, Amini N. et al. Outcomes of minimally invasive vs. open pancreatoduodenectomies in pancreatic adenocarcinoma: analysis of ACS-NSQIP data. Langenbecks Arch Surg 2024; 409 (01) 258
• 38 Liu R, Abu Hilal M, Besselink MG. et al. International consensus guidelines on robotic pancreatic surgery in 2023. Hepatobiliary Surg Nutr 2024; 13 (01) 89-104
• 39 van Hilst J, de Rooij T, Bosscha K. et al; Dutch Pancreatic Cancer Group. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial. Lancet Gastroenterol Hepatol 2019; 4 (03) 199-207
• 40 de Graaf N, Augustinus S, Wellner UF. et al; Global Audits on Pancreatic Surgery Group (GAPASURG). Transatlantic differences in the use and outcome of minimally invasive pancreatoduodenectomy: an international multi-registry analysis. Surg Endosc 2024; 38 (12) 7099-7111
• 41 Hirono S, Yamaue H. Surgical strategy for intraductal papillary mucinous neoplasms of the pancreas. Surg Today 2020; 50 (01) 50-55
• 42 Ideno N, Nakata K, Nakamura M. What are the appropriate surgery and postoperative surveillance for intraductal papillary mucinous neoplasm?. J Dig Cancer Rep 2021; 9: 8-18
• 43 Pausch TM, Liu X, Dincher J. et al. Middle segment-preserving pancreatectomy to avoid pancreatic insufficiency: individual patient data analysis of all published cases from 2003-2021. J Clin Med 2023; 12 (05) 2013
• 44 Turrini O, Schmidt CM, Pitt HA. et al. Side-branch intraductal papillary mucinous neoplasms of the pancreatic head/uncinate: resection or enucleation?. HPB (Oxford) 2011; 13 (02) 126-131
• 45 Ratnayake CB, Biela C, Windsor JA, Pandanaboyana S. Enucleation for branch duct intraductal papillary mucinous neoplasms: a systematic review and meta-analysis. HPB (Oxford) 2019; 21 (12) 1593-1602
• 46 Kaiser J, Fritz S, Klauss M. et al. Enucleation: a treatment alternative for branch duct intraductal papillary mucinous neoplasms. Surgery 2017; 161 (03) 602-610
• 47 Dakubo GD, Jakupciak JP, Birch-Machin MA, Parr RL. Clinical implications and utility of field cancerization. Cancer Cell Int 2007; 7: 2
• 48 Kaneko T, Nakao A, Nomoto S. et al. Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas. Arch Surg 1998; 133 (03) 263-267
• 49 Fujii T, Kato K, Kodera Y. et al. Prognostic impact of pancreatic margin status in the intraductal papillary mucinous neoplasms of the pancreas. Surgery 2010; 148 (02) 285-290
• 50 Dhar VK, Merchant NB, Patel SH. et al. Does surgical margin impact recurrence in noninvasive intraductal papillary mucinous neoplasms?: A multi-institutional study. Ann Surg 2018; 268 (03) 469-478
• 51 Kim HS, Han Y, Kang JS. et al. 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 2022; 276 (04) e231-e238
• 52 Sauvanet A, Couvelard A, Belghiti J. Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas. World J Gastrointest Surg 2010; 2 (10) 352-358
• 53 Chi Z, Dhall D, Mertens R. 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 2022; 51 (01) 63-74
• 54 de Jong DM, Stassen PMC, Groot Koerkamp B. et al; European Cholangioscopy Study Group. The role of pancreatoscopy in the diagnostic work-up of intraductal papillary mucinous neoplasms: a systematic review and meta-analysis. Endoscopy 2023; 55 (01) 25-35
• 55 Adsay V, Mino-Kenudson M, Furukawa T. et al; Members of Verona Consensus Meeting, 2013. 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 2016; 263 (01) 162-177
• 56 Mino-Kenudson M, Fernández-del Castillo C, Baba Y. et al. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut 2011; 60 (12) 1712-1720
• 57 Neoptolemos JP, Stocken DD, Friess H. et al; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004; 350 (12) 1200-1210
• 58 Marchegiani G, Andrianello S, Dal Borgo C. et al. Adjuvant chemotherapy is associated with improved postoperative survival in specific subtypes of invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas: it is time for randomized controlled data. HPB (Oxford) 2019; 21 (05) 596-603
• 59 Chong E, Ratnayake B, Dasari BVM, Loveday BPT, Siriwardena AK, Pandanaboyana S. Adjuvant Chemotherapy in the Treatment of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Systematic Review and Meta-Analysis. World J Surg 2022; 46 (01) 223-234
• 60 Swartz MJ, Hsu CC, Pawlik TM. et al. Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas. Int J Radiat Oncol Biol Phys 2010; 76 (03) 839-844
• 61 McMillan MT, Lewis RS, Drebin JA. et al. The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN). Cancer 2016; 122 (04) 521-533
• 62 Correa-Gallego C, Miyasaka Y, Hozaka Y. et al. Surveillance after resection of non-invasive intraductal papillary mucinous neoplasms (IPMN). A systematic review. Pancreatology 2023; 23 (03) 258-265
• 63 Ohtsuka T, Kono H, Tanabe R. et al. Follow-up study after resection of intraductal papillary mucinous neoplasm of the pancreas; special references to the multifocal lesions and development of ductal carcinoma in the remnant pancreas. Am J Surg 2012; 204 (01) 44-48
• 64 Fujita M, Itoi T, Ikeuchi N. et al. Effectiveness of contrast-enhanced endoscopic ultrasound for detecting mural nodules in intraductal papillary mucinous neoplasm of the pancreas and for making therapeutic decisions. Endosc Ultrasound 2016; 5 (06) 377-383
• 65 Chari ST, Yadav D, Smyrk TC. et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology 2002; 123 (05) 1500-1507
• 66 Schnelldorfer T, Sarr MG, Nagorney DM. et al. Experience with 208 resections for intraductal papillary mucinous neoplasm of the pancreas. Arch Surg 2008; 143 (07) 639-646 , discussion 646
• 67 Winner M, Epelboym I, Remotti H. et al. Predictors of recurrence in intraductal papillary mucinous neoplasm: experience with 183 pancreatic resections. J Gastrointest Surg 2013; 17 (09) 1618-1626
• 68 Marchegiani G, Mino-Kenudson M, Ferrone CR. et al. Patterns of recurrence after resection of IPMN: who, when, and how?. Ann Surg 2015; 262 (06) 1108-1114
• 69 Dresler CM, Fortner JG, McDermott K, Bajorunas DR. Metabolic consequences of (regional) total pancreatectomy. Ann Surg 1991; 214 (02) 131-140
• 70 Pulvirenti A, Pea A, Rezaee N. et al. Perioperative outcomes and long-term quality of life after total pancreatectomy. Br J Surg 2019; 106 (13) 1819-1828