The research progress of intraductal papillary mucinous neoplasms_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Tong , HUANG Zixing ,  SONG Bin

Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

SONG Bin, Email: cjr.songbin@vip.163.com

Keywords：

intraductal papillary mucinous neoplasms; diagnosis; molecular biology; review

DOI：

10.7507/1007-9424.201702074

Video：

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Objective To summarize the research progress of intraductal papillary mucinous neoplasms (IPMNs). Method The domestic and international published literatures related to IPMNs in recent years were collected and reviewed． Results Based on the site of tumor involved, IPMNs were classified into main duct, branch duct, and mixed types. According to the histologic features, IPMNs were divided into intestinal, pancreatobiliary, gastric, and oncocytic types. The pathological and clinical presentations of IPMNs were vary, and multiple imaging approaches including endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography (EUS), CT, magnetic resonance cholangiopancreatography (MRCP) combined with MRI, could display morphologic and functional characteristics of IPMNs. In additon, the risk of malignancy in IPMNs could be evaluated and the functions of some genes (including KRAS, BRAF, GNAS, and so on) in the development process of IPMNs had been confirmed. Conclusion IPMNs is a kind of disease different from other tumors of the pancreas in clinicopathologic features, imaging performance, and molecular biology changes, and how to link the above three aspects needs to be further studied.

Citation： ZHANG Tong, HUANG Zixing, SONG Bin. The research progress of intraductal papillary mucinous neoplasms. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(3): 376-380. doi: 10.7507/1007-9424.201702074 Copy

1.	Tanaka M, Fernández-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): 183-197.
2.	Koh YX, Zheng HL, Chok AY, et al. Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms. Surgery, 2015, 157(3): 496-509.
3.	Fong ZV, Ferrone CR, Lillemoe KD, et al. Intraductal papillary mucinous neoplasm of the pancreas: current state of the art and ongoing controversies. Ann Surg, 2016, 263(5): 908-917.
4.	Distler M, Kersting S, Niedergethmann M, et al. Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg, 2013, 258(2): 324-330.
5.	Sugiyama M, Izumisato Y, Abe N, et al. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas. Br J Surg, 2003, 90(10): 1244-1249.
6.	Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg, 2004, 239(6): 788-799.
7.	高春涛, 赫继辉. 胰腺导管内乳头状黏液性肿瘤诊疗进展. 中国肿瘤临床, 2010, 37(23): 1377-1379.
8.	Jeurnink SM, Vleggaar FP, Siersema PD. Overview of the clinical problem: facts and current issues of mucinous cystic neoplasms of the pancreas. Dig Liver Dis, 2008, 40(11): 837-846.
9.	Salvia R, Fernández-del Castillo C, Bassi C, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg, 2004, 239(5): 678-687.
10.	Carrara S, Cangi MG, Arcidiacono PG, et al. Mucin expression pattern in pancreatic diseases: findings from EUS-guided fine-needle aspiration biopsies. Am J Gastroenterol, 2011, 106(7): 1359-1363.
11.	Waters JA, Schmidt CM, Pinchot JW, et al. CTvs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg, 2008, 12(1): 101-109.
12.	Sand J, Nordback I. The differentiation between pancreatic neoplastic cysts and pancreatic pseudocyst. Scand J Surg, 2005, 94(2): 161-164.
13.	Sakorafas GH, Sarr MG. Cystic neoplasms of the pancreas; what a clinician should know. Cancer Treat Rev, 2005, 31(7): 507-535.
14.	Kawamoto S, Lawler LP, Horton KM, et al. MDCT of intraductal papillary mucinous neoplasm of the pancreas: evaluation of features predictive of invasive carcinoma. AJR Am J Roentgenol, 2006, 186(3): 687-695.
15.	Jones MJ, Buchanan AS, Neal CP, et al. Imaging of indeterminate pancreatic cystic lesions: a systematic review. Pancreatology, 2013, 13(4): 436-442.
16.	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(1-2): 17-32.
17.	Fritz S, Klauss M, Bergmann F, et al. Small (Sendai negative) branch-duct IPMNs: not harmless. Ann Surg, 2012, 256(2): 313-320.
18.	Kamata K, Kitano M, Kudo M, et al. Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms. Endoscopy, 2014, 46(1): 22-29.
19.	Ogawa T, Horaguchi J, Fujita N, et al. Diffusion-weighted magnetic resonance imaging for evaluating the histological degree of malignancy in patients with intraductal papillary mucinous neoplasm. J Hepatobiliary Pancreat Sci, 2014, 21(11): 801-808.
20.	Kang KM, Lee JM, Shin CI, et al. Added value of diffusion-weighted imaging to MR cholangiopancreatography with unenhanced mr imaging for predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm of the pancreas. J Magn Reson Imaging, 2013, 38(3): 555-563.
21.	Kang KM, Lee JM, Yoon JH, et al. Intravoxel incoherent motion diffusion-weighted MR imaging for characterization of focal pancreatic lesions. Radiology, 2014, 270(2): 444-453.
22.	Nishihara K, Fukuda T, Tsuneyoshi M, et al. Intraductal papillary neoplasm of the pancreas. Cancer, 1993, 72(3): 689-696.
23.	Nodari F, Baiocchi GL, Salvi A, et al. Telomerase gene expression in intraductal papillary-mucinous tumors (IPMT): preliminary findings. Acta Biomed, 2003, 74 Suppl 2: 59-64.
24.	Yonaiyama S, Toyoki Y, Morohashi S, et al. Epithelial cell adhesion molecule (EpCAM) overexpression is correlated with malignant potentials of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Biomed Res, 2013, 34(2): 87-95.
25.	Tamahashi U, Kumagai J, Takizawa T, et al. Expression and intracellular localization of matrix metalloproteinases in intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch, 2008, 453(1): 79-87.
26.	Sessa F, Solcia E, Capella C, et al. Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch, 1994, 425(4): 357-367.
27.	Kondo H, Sugano K, Fukayama N, et al. Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas. Cancer, 1997, 79(5): 900-905.
28.	Hong SM, Vincent A, Kanda M, et al. Genome-wide somatic copy number alterations in low-grade PanINs and IPMNs from individuals with a family history of pancreatic cancer. Clin Cancer Res, 2012, 18(16): 4303-4312.
29.	Tada M, Omata M, Ohto M. Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases. Cancer, 1991, 67(3): 634-637.
30.	Lemoine NR, Jain S, Hughes CM, et al. Ki-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology, 1992, 102(1): 230-236.
31.	Schönleben F, Qiu W, Bruckman KC, et al. BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas. Cancer Lett, 2007, 249(2): 242-248.
32.	Wu J, Matthaei H, Maitra A, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med, 2011, 3(92): 92ra66.
33.	Dal Molin M, Matthaei H, Wu J, et al. Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg Oncol, 2013, 20(12): 3802-3808.
34.	Amato E, Molin MD, Mafficini A, et al. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol, 2014, 233(3): 217-227.
35.	Furukawa T, Kuboki Y, Tanji E, et al. Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep, 2011, 1: 161.
36.	Wu J, Jiao Y, Dal Molin M, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A, 2011, 108(52): 21188-21193.

1. Tanaka M, Fernández-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): 183-197.
2. Koh YX, Zheng HL, Chok AY, et al. Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms. Surgery, 2015, 157(3): 496-509.
3. Fong ZV, Ferrone CR, Lillemoe KD, et al. Intraductal papillary mucinous neoplasm of the pancreas: current state of the art and ongoing controversies. Ann Surg, 2016, 263(5): 908-917.
4. Distler M, Kersting S, Niedergethmann M, et al. Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg, 2013, 258(2): 324-330.
5. Sugiyama M, Izumisato Y, Abe N, et al. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas. Br J Surg, 2003, 90(10): 1244-1249.
6. Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg, 2004, 239(6): 788-799.
7. 高春涛, 赫继辉. 胰腺导管内乳头状黏液性肿瘤诊疗进展. 中国肿瘤临床, 2010, 37(23): 1377-1379.
8. Jeurnink SM, Vleggaar FP, Siersema PD. Overview of the clinical problem: facts and current issues of mucinous cystic neoplasms of the pancreas. Dig Liver Dis, 2008, 40(11): 837-846.
9. Salvia R, Fernández-del Castillo C, Bassi C, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg, 2004, 239(5): 678-687.
10. Carrara S, Cangi MG, Arcidiacono PG, et al. Mucin expression pattern in pancreatic diseases: findings from EUS-guided fine-needle aspiration biopsies. Am J Gastroenterol, 2011, 106(7): 1359-1363.
11. Waters JA, Schmidt CM, Pinchot JW, et al. CTvs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg, 2008, 12(1): 101-109.
12. Sand J, Nordback I. The differentiation between pancreatic neoplastic cysts and pancreatic pseudocyst. Scand J Surg, 2005, 94(2): 161-164.
13. Sakorafas GH, Sarr MG. Cystic neoplasms of the pancreas; what a clinician should know. Cancer Treat Rev, 2005, 31(7): 507-535.
14. Kawamoto S, Lawler LP, Horton KM, et al. MDCT of intraductal papillary mucinous neoplasm of the pancreas: evaluation of features predictive of invasive carcinoma. AJR Am J Roentgenol, 2006, 186(3): 687-695.
15. Jones MJ, Buchanan AS, Neal CP, et al. Imaging of indeterminate pancreatic cystic lesions: a systematic review. Pancreatology, 2013, 13(4): 436-442.
16. 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(1-2): 17-32.
17. Fritz S, Klauss M, Bergmann F, et al. Small (Sendai negative) branch-duct IPMNs: not harmless. Ann Surg, 2012, 256(2): 313-320.
18. Kamata K, Kitano M, Kudo M, et al. Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms. Endoscopy, 2014, 46(1): 22-29.
19. Ogawa T, Horaguchi J, Fujita N, et al. Diffusion-weighted magnetic resonance imaging for evaluating the histological degree of malignancy in patients with intraductal papillary mucinous neoplasm. J Hepatobiliary Pancreat Sci, 2014, 21(11): 801-808.
20. Kang KM, Lee JM, Shin CI, et al. Added value of diffusion-weighted imaging to MR cholangiopancreatography with unenhanced mr imaging for predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm of the pancreas. J Magn Reson Imaging, 2013, 38(3): 555-563.
21. Kang KM, Lee JM, Yoon JH, et al. Intravoxel incoherent motion diffusion-weighted MR imaging for characterization of focal pancreatic lesions. Radiology, 2014, 270(2): 444-453.
22. Nishihara K, Fukuda T, Tsuneyoshi M, et al. Intraductal papillary neoplasm of the pancreas. Cancer, 1993, 72(3): 689-696.
23. Nodari F, Baiocchi GL, Salvi A, et al. Telomerase gene expression in intraductal papillary-mucinous tumors (IPMT): preliminary findings. Acta Biomed, 2003, 74 Suppl 2: 59-64.
24. Yonaiyama S, Toyoki Y, Morohashi S, et al. Epithelial cell adhesion molecule (EpCAM) overexpression is correlated with malignant potentials of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Biomed Res, 2013, 34(2): 87-95.
25. Tamahashi U, Kumagai J, Takizawa T, et al. Expression and intracellular localization of matrix metalloproteinases in intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch, 2008, 453(1): 79-87.
26. Sessa F, Solcia E, Capella C, et al. Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch, 1994, 425(4): 357-367.
27. Kondo H, Sugano K, Fukayama N, et al. Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas. Cancer, 1997, 79(5): 900-905.
28. Hong SM, Vincent A, Kanda M, et al. Genome-wide somatic copy number alterations in low-grade PanINs and IPMNs from individuals with a family history of pancreatic cancer. Clin Cancer Res, 2012, 18(16): 4303-4312.
29. Tada M, Omata M, Ohto M. Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases. Cancer, 1991, 67(3): 634-637.
30. Lemoine NR, Jain S, Hughes CM, et al. Ki-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology, 1992, 102(1): 230-236.
31. Schönleben F, Qiu W, Bruckman KC, et al. BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas. Cancer Lett, 2007, 249(2): 242-248.
32. Wu J, Matthaei H, Maitra A, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med, 2011, 3(92): 92ra66.
33. Dal Molin M, Matthaei H, Wu J, et al. Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg Oncol, 2013, 20(12): 3802-3808.
34. Amato E, Molin MD, Mafficini A, et al. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol, 2014, 233(3): 217-227.
35. Furukawa T, Kuboki Y, Tanji E, et al. Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep, 2011, 1: 161.
36. Wu J, Jiao Y, Dal Molin M, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A, 2011, 108(52): 21188-21193.

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