Skip to main content

Advertisement

SpringerLink
Log in

Risk of additional pancreatic cancer in patients with branch duct intraductal papillary-mucinous neoplasm

  • Clinical Review
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Branch duct intraductal papillary-mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency. Although BD-IPMN outcomes are generally good, pancreatic ductal adenocarcinoma (PDA) is found distant from the original BD-IPMN in about 3.3–9.2% of cases. These reports raise the question of whether a possible association exists between BD-IPMN and PDA. Recent findings from follow-up studies suggest that pancreases with BD-IPMNs have a high risk of developing additional pancreatic cancer, with standardized incidence ratios (SIRs) of 15.8- to 26-fold. These studies suggest that special attention should be paid to BD-IPMN patients who are ≥70 years. Furthermore, molecular evidence supports the hypothesis that field cancerization causing multiple primary neoplastic lesions exists in pancreases harboring IPMNs. Although more extensive studies are required to clarify the magnitude of this increased risk, clinicians should pay close attention to the development of PDA in patients with BD-IPMN, as well as to changes in BD-IPMN lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IPMN:

Intraductal papillary-mucinous neoplasm

PDA:

Pancreatic ductal adenocarcinoma

PanIN:

Pancreatic intraepithelial neoplasia

References

  1. Loftus EV Jr, Olivares-Pakzad BA, Batts KP, Adkins MC, Stephens DH, Sarr MG, et al. Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic. Gastroenterology. 1996;110:1909–18.

    Article  PubMed  Google Scholar 

  2. Azar C, Van de Stadt J, Rickaert F, Deviere M, Baize M, Kloppel G, et al. Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients. Gut. 1996;39:457–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rivera JA, Fernandez-del Castillo C, Pins M, Compton CC, Lewandrowski KB, Rattner DW, et al. Pancreatic mucinous ductal ectasia and intraductal papillary neoplasms. A single malignant clinicopathologic entity. Ann Surg. 1997;225:637–44. (discussion 644–6).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Morohoshi T, Kanda M, Asanuma K, Kloppel G. Intraductal papillary neoplasms of the pancreas. A clinicopathologic study of six patients. Cancer. 1989;64:1329–35.

    Article  CAS  PubMed  Google Scholar 

  5. Rickaert F, Cremer M, Deviere J, Tavares L, Lambilliotte JP, Schroder S, et al. Intraductal mucin-hypersecreting neoplasms of the pancreas. A clinicopathologic study of eight patients. Gastroenterology. 1991;101:512–9.

    Article  CAS  PubMed  Google Scholar 

  6. Obara T, Maguchi H, Saitoh Y, Ura H, Koike Y, Kitazawa S, et al. Mucin-producing tumor of the pancreas: a unique clinical entity. Am J Gastroenterol. 1991;86:1619–25.

    CAS  PubMed  Google Scholar 

  7. Yamada M, Kozuka S, Yamao K, Nakazawa S, Naitoh Y, Tsukamoto Y. Mucin-producing tumor of the pancreas. Cancer. 1991;68:159–68.

    Article  CAS  PubMed  Google Scholar 

  8. Tanno S, Nakano Y, Nishikawa T, Nakamura K, Sasajima J, Minoguchi M, et al. Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results. Gut. 2008;57:339–43.

    Article  CAS  PubMed  Google Scholar 

  9. Tanaka M, Kobayashi K, Mizumoto K, Yamaguchi K. Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol. 2005;40:669–75.

    Article  PubMed  Google Scholar 

  10. Traverso LW, Peralta EA, Ryan JA Jr, Kozarek RA. Intraductal neoplasms of the pancreas. Am J Surg. 1998;175:426–32.

    Article  CAS  PubMed  Google Scholar 

  11. Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004;239:788–97.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rodriguez JR, Salvia R, Crippa S, Warshaw AL, Bassi C, Falconi M, et al. Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection. Gastroenterology. 2007;133:72–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Salvia R, Fernandez-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004;239:678–85.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schmidt CM, White PB, Waters JA, Yiannoutsos CT, Cummings OW, Baker M, et al. Intraductal papillary mucinous neoplasms: predictors of malignant and invasive pathology. Ann Surg. 2007;246:644–51.

    Article  PubMed  Google Scholar 

  15. Bernard P, Scoazec JY, Joubert M, Kahn X, Le Borgne J, Berger F, et al. Intraductal papillary-mucinous tumors of the pancreas: predictive criteria of malignancy according to pathological examination of 53 cases. Arch Surg. 2002;137:1274–8.

    Article  PubMed  Google Scholar 

  16. Obara T, Saitoh Y, Maguchi H, Ura H, Kitazawa S, Koike Y, et al. Multicentric development of pancreatic intraductal carcinoma through atypical papillary hyperplasia. Hum Pathol. 1992;23:82–5.

    Article  CAS  PubMed  Google Scholar 

  17. Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32.

    Article  PubMed  Google Scholar 

  18. Fernandez-del Castillo C, Targarona J, Thayer SP, Rattner DW, Brugge WR, Warshaw AL. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg. 2003;138:427–33.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Salvia R, Crippa S, Falconi M, Bassi C, Guarise A, Scarpa A, et al. Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate? Gut. 2007;56:1086–90.

    Article  PubMed  Google Scholar 

  20. Sohn TA, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg. 2001;234:313–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tada M, Kawabe T, Arizumi M, Togawa O, Matsubara S, Yamamoto N, et al. Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study in 197 patients. Clin Gastroenterol Hepatol. 2006;4:1265–70.

    Article  PubMed  Google Scholar 

  22. Yamaguchi K, Ohuchida J, Ohtsuka T, Nakano K, Tanaka M. Intraductal papillary-mucinous tumor of the pancreas concomitant with ductal carcinoma of the pancreas. Pancreatology. 2002;2:484–90.

    Article  PubMed  Google Scholar 

  23. Komori T, Ishikawa O, Ohigashi H, Yamada T, Sasaki Y, Imaoka S, et al. Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation. Jpn J Clin Oncol. 2002;32:146–51.

    Article  PubMed  Google Scholar 

  24. Adsay NV. The “new kid on the block”: intraductal papillary mucinous neoplasms of the pancreas: current concepts and controversies. Surgery. 2003;133:459–63.

    Article  PubMed  Google Scholar 

  25. Kobayashi G, Fujita N, Noda Y, Ito K, Horaguchi J, Takasawa O. Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS. J Gastroenterol. 2005;40:744–51.

    Article  PubMed  Google Scholar 

  26. Tanno S, Nakano Y, Sugiyama Y, Nakamura K, Sasajima J, Koizumi K, et al. Incidence of synchronous and metachronous pancreatic carcinoma in 168 patients with branch duct intraductal papillary-mucinous neoplasm. Pancreatology. 2009. (in press).

  27. Tanno S, Nakano Y, Koizumi K, Sugiyama Y, Nakamura K, Sasajima J, et al. Pancreatic ductal adenocarcinoma in long-term follow-up patients with branch duct intraductal papillary-mucinous neoplasms. Pancreas. 2009. (in press).

  28. Uehara H, Nakaizumi A, Ishikawa O, Iishi H, Tatsumi K, Takakura R, et al. Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas. Gut. 2008;57:1561–5.

    Article  CAS  PubMed  Google Scholar 

  29. Biankin AV, Kench JG, Biankin SA, Lee CS, Morey AL, Dijkman FP, et al. Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence. Am J Surg Pathol. 2004;28:1184–92.

    Article  PubMed  Google Scholar 

  30. Greenhalf W. An unfavourable prognosis for pancreatic cancer indicates fields of opportunity. Gut. 2006;55:1533–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28:977–87.

    Article  PubMed  Google Scholar 

  32. Izawa T, Obara T, Tanno S, Mizukami Y, Yanagawa N, Kohgo Y. Clonality and field cancerization in intraductal papillary-mucinous tumors of the pancreas. Cancer. 2001;92:1807–17.

    Article  CAS  PubMed  Google Scholar 

  33. Hruban RH, Takaori K, Canto M, Fishman EK, Campbell K, Brune K, et al. Clinical importance of precursor lesions in the pancreas. J Hepatobiliary Pancreat Surg. 2007;14:255–63.

    Article  PubMed  Google Scholar 

  34. Hruban RH, Maitra A, Kern SE, Goggins M. Precursors to pancreatic cancer. Gastroenterol Clin North Am. 2007;36:831–49.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Launois B, Franci J, Bardaxoglou E, Ramee MP, Paul JL, Malledant Y. Total pancreatectomy for ductal adenocarcinoma of the pancreas with special reference to resection of the portal vein and multicentric cancer. World J Surg. 1993;17:122–6. (discussion 126–7).

    Article  CAS  PubMed  Google Scholar 

  36. Z’Graggen K, Rivera JA, Compton CC, Pins M, Werner J, Fernandez-del Castillo C, et al. Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Ann Surg. 1997;226:491–8. (discussion 498–500).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Caldas C, Kern SE. K-ras mutation and pancreatic adenocarcinoma. Int J Pancreatol. 1995;18:1–6.

    CAS  PubMed  Google Scholar 

  38. Yanagisawa A, Kato Y, Ohtake K, Kitagawa T, Ohashi K, Hori M, et al. C-ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas. Jpn J Cancer Res. 1991;82:1057–60.

    Article  CAS  PubMed  Google Scholar 

  39. Yanagisawa A, Ohtake K, Ohashi K, Hori M, Kitagawa T, Sugano H, et al. Frequent c-ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. Cancer Res. 1993;53:953–6.

    CAS  PubMed  Google Scholar 

  40. Tada M, Ohashi M, Shiratori Y, Okudaira T, Komatsu Y, Kawabe T, et al. Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease. Gastroenterology. 1996;110:227–31.

    Article  CAS  PubMed  Google Scholar 

  41. Tada M, Omata M, Ohto M. Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases. Cancer. 1991;67:634–7.

    Article  CAS  PubMed  Google Scholar 

  42. Sessa F, Solcia E, Capella C, Bonato M, Scarpa A, Zamboni G, 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;425:357–67.

    Article  CAS  PubMed  Google Scholar 

  43. Hoshi T, Imai M, Ogawa K. Frequent K-ras mutations and absence of p53 mutations in mucin-producing tumors of the pancreas. J Surg Oncol. 1994;55:84–91.

    Article  CAS  PubMed  Google Scholar 

  44. Terhune PG, Phifer DM, Tosteson TD, Longnecker DS. K-ras mutation in focal proliferative lesions of human pancreas. Cancer Epidemiol Biomarkers Prev. 1998;7:515–21.

    CAS  PubMed  Google Scholar 

  45. Matsubayashi H, Watanabe H, Yamaguchi T, Ajioka Y, Nishikura K, Iwafuchi M, et al. Multiple K-ras mutations in hyperplasia and carcinoma in cases of human pancreatic carcinoma. Jpn J Cancer Res. 1999;90:841–8.

    Article  CAS  PubMed  Google Scholar 

  46. Moskaluk CA, Hruban RH, Kern SE. P16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 1997;57:2140–3.

    CAS  PubMed  Google Scholar 

  47. Wilentz RE, Geradts J, Maynard R, Offerhaus GJ, Kang M, Goggins M, et al. Inactivation of the p16 (ink4a) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res. 1998;58:4740–4.

    CAS  PubMed  Google Scholar 

  48. Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4:437–50.

    Article  CAS  PubMed  Google Scholar 

  49. Siveke JT, Einwachter H, Sipos B, Lubeseder-Martellato C, Kloppel G, Schmid RM. Concomitant pancreatic activation of kras(g12d) and tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 2007;12:266–79.

    Article  CAS  PubMed  Google Scholar 

  50. Novelli MR, Williamson JA, Tomlinson IP, Elia G, Hodgson SV, Talbot IC, et al. Polyclonal origin of colonic adenomas in an xo/xy patient with fap. Science. 1996;272:1187–90.

    Article  CAS  PubMed  Google Scholar 

  51. Perren A, Roth J, Muletta-Feurer S, Saremaslani P, Speel EJ, Heitz PU, et al. Clonal analysis of sporadic pancreatic endocrine tumours. J Pathol. 1998;186:363–71.

    Article  CAS  PubMed  Google Scholar 

  52. Noguchi S, Motomura K, Inaji H, Imaoka S, Koyama H. Clonal analysis of fibroadenoma and phyllodes tumor of the breast. Cancer Res. 1993;53:4071–4.

    CAS  PubMed  Google Scholar 

  53. Sidransky D, Frost P, Von Eschenbach A, Oyasu R, Preisinger AC, Vogelstein B. Clonal origin bladder cancer. N Engl J Med. 1992;326:737–40.

    Article  CAS  PubMed  Google Scholar 

  54. Motojima K, Urano T, Nagata Y, Shiku H, Tsurifune T, Kanematsu T. Detection of point mutations in the kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma. Ann Surg. 1993;217:138–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Fujii T, Obara T, Maguchi H, Tanno S, Ura H, Kohgo Y. Clinicopathologic study of multiple mucin-producing tumors of the pancreas: multicentric development of carcinoma through atypical hyperplasia. J Jpn Pancreat Soc. 1996;11:344–52.

    Google Scholar 

  56. Inagaki M, Maguchi M, Kino S, Obara M, Ishizaki A, Onodera K, et al. Mucin-producing tumors of the pancreas: clinicopathological features, surgical treatment, and outcome. J Hepatobiliary Pancreat Surg. 1999;6:281–5.

    Article  CAS  PubMed  Google Scholar 

  57. Bendix Holme J, Jacobsen N, Rokkjaer M, Kruse A. Total pancreatectomy in six patients with intraductal papillary mucinous tumour of the pancreas: the treatment of choice. HPB (Oxford). 2001;3:257–62.

    Article  CAS  Google Scholar 

  58. Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS. Intraductal papillary-mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer. 2002;94:62–77.

    Article  PubMed  Google Scholar 

  59. Fukushima N, Mukai K, Kanai Y, Hasebe T, Shimada K, Ozaki H, et al. Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases. Hum Pathol. 1997;28:1010–7.

    Article  CAS  PubMed  Google Scholar 

  60. Nagai E, Ueki T, Chijiiwa K, Tanaka M, Tsuneyoshi M. Intraductal papillary mucinous neoplasms of the pancreas associated with so-called “Mucinous ductal ectasia”. Histochemical and immunohistochemical analysis of 29 cases. Am J Surg Pathol. 1995;19:576–89.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

No conflicts of interest exist.

Author information

Authors and Affiliations

  1. Department of General Medicine, Asahikawa Medical College, 2-1-1-1 East Midorigaoka, Asahikawa, Hokkaido, 078-8510, Japan

    Satoshi Tanno

  2. Department of Gastroenterology and Hematology/Oncology, Asahikawa Medical College, Asahikawa, Japan

    Takeshi Obara, Kazuya Koizumi, Yasuhiro Nakano, Manabu Osanai, Yusuke Mizukami & Yutaka Kohgo

Authors
  1. Satoshi Tanno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Obara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuya Koizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuhiro Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manabu Osanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yusuke Mizukami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yutaka Kohgo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoshi Tanno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanno, S., Obara, T., Koizumi, K. et al. Risk of additional pancreatic cancer in patients with branch duct intraductal papillary-mucinous neoplasm. Clin J Gastroenterol 2, 365–370 (2009). https://doi.org/10.1007/s12328-009-0116-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-009-0116-6

Keywords

Search

Navigation