Skip to main content
SpringerLink
Log in

Screening for Pancreatic Cancer in a High-Risk Cohort: An Eight-Year Experience

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

Pancreatic adenocarcinoma is the fourth leading cause of cancer death.

Methods

A prospective cohort study was undertaken between 2003 and 2011 at a tertiary care centre in Toronto, Canada. Two hundred and sixty-two subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations and/or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected. Evidence of malignancy or suspicious macroscopic abnormalities prompted referral for surgical intervention.

Results

Average length of follow-up was 4.2 years, during which 84/262 (32%) subjects demonstrated pancreatic abnormalities. Three participants developed pancreatic adenocarcinoma (one 1.5-cm tumor was resected but recurred, while the other two subjects developed metastatic cancer), and a fourth participant developed a pancreatic neuroendocrine tumor that was resected. Fifteen subjects had radiologic evidence of branch-duct intraductal papillary mucinous neoplasms, of which two underwent surgical resection. Sixty-five subjects had simple pancreatic cysts that have remained stable.

Conclusion

Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, but further improvement in sensitivity is needed. An understanding of the natural history of pre-invasive lesions in members of high-risk families is necessary for developing a more effective screening program.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK (eds). SEER Cancer Statistics Review, 1975–2007, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2007/, based on November 2009 SEER data submission, posted to the SEER website 2010.

  2. Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2010. Toronto: Canadian Cancer Society, 2010.

    Google Scholar 

  3. Di Marco M, Di Cicilia R, Macchini M, Nobili E, Vecchiarelli S, Brandi G, Biasco G. Metastatic pancreatic cancer: is gemcitabine still the best standard treatment? Oncol Rep 2010;23:1183–1192.

    PubMed  Google Scholar 

  4. Steinberg WM, Barkin JS, Bradley EL III, DiMagno E, Layer P, Canto MI, Levy MJ. Should patients with a strong family history of pancreatic cancer be screened on a periodic basis for cancer of the pancreas? Pancreas 2009;38:e137–150.

    Article  PubMed  Google Scholar 

  5. Tanaka M, Kobayashi K, Mizumoto K, Yamaguchi K. Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol 2005;40:669–675.

    Article  PubMed  Google Scholar 

  6. Tanno S, Nakano Y, Sugiyama Y, Nakamura K, Sasajima J, Koizumi K, Yamazaki M, Nishikawa T, Mizukami Y, Yanagawa N, Fujii T, Obara T, Okumura T, Kohgo Y. Incidence of synchronous and metachronous pancreatic carcinoma in 168 patients with branch duct intraductal papillary mucinous neoplasm. Pancreatology 2010;10:173–178.

    Article  PubMed  Google Scholar 

  7. Ikeuchi N, Itoi T, Sofuni A, Itokawa F, Tsuchiya T, Kurihara T, Ishii K, Tsuji S, Umeda J, Moriyasu F, Tsuchida A, Kasuya K. Prognosis of cancer with branch duct type IPMN of the pancreas. World J Gastroenterol 2010;16:1890–1895.

    Article  PubMed  Google Scholar 

  8. Hruban RH, Canto MI, Goggins M, Schulick R, Klein AP. Update on familial pancreatic cancer. Adv Surg 2010;44:293–311.

    Article  PubMed  Google Scholar 

  9. Goldstein AM, Fraser MC, Struewing JP, Hussussian CJ, Ranade K, Zametkin DP, Fontaine LS, Organic SM, Dracopoli NC, Clark WH Jr, Tucker MA. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995;333:970–974.

    Article  PubMed  CAS  Google Scholar 

  10. De Snoo FA, Bishop DT, Bergman W, van Leeuwen I, van der Drift C, van Nieuwpoort FA, Out-Luiting CJ, Vasen HF, ter Huurne JA, Frants RR, Willemze R, Breuning MH, Gruis NA. Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clin Cancer Res 2008;14:7151–7157.

    Article  PubMed  Google Scholar 

  11. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000;119:1447–1153.

    Article  PubMed  CAS  Google Scholar 

  12. Lowenfels AB, Maisonneuve P, DiMagno EP, Elitsur Y, Gates LK Jr, Perrault J, Whitcomb DC. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997;89:442–446

    Article  PubMed  CAS  Google Scholar 

  13. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310–1316.

    Article  Google Scholar 

  14. van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Hoogerbrugge N, Verhoef S, Vasen HF, Ausems MG, Menko FH, Gomez Garcia EB, Klijn JG, Hogervorst FB, van Houwelingen JC, van’t Veer LJ, Rookus MA, van Leeuwen FE; Netherlands Collaborative Group on Hereditary Breast Cancer (HEBON). Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 2005;42:711–719

    Article  PubMed  Google Scholar 

  15. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, Tang J, Li S, Zhang S, Shaw PA, Narod SA. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 2006;98:1694–1706.

    Article  PubMed  CAS  Google Scholar 

  16. Shirts BH, Burt RW, Mulvihill SJ, Cannon-Albright LA. A population-based description of familial clustering of pancreatic cancer. Clin Gastroenterol Hepatol 2010;8:812–816.

    Article  PubMed  Google Scholar 

  17. Brune KA, Lau B, Palmisano E, Canto M, and Goggins MG, Hruban RH, Klein AP. Importance of age of onset in pancreatic cancer kindreds. J Natl Cancer Inst 2010;102:119–126.

    Article  PubMed  Google Scholar 

  18. Jacobs EJ, Chanock SJ, Fuchs CS, Lacroix A, McWilliams RR, Steplowski E, Stolzenberg-Solomon RZ, Arslan AA, Bueno-de-Mesquita HB, Gross M, Helzlsouer K, Petersen G, Zheng W, Agalliu I, Allen NE, Amundadottir L, Boutron-Ruault MC, Buring JE, Canzian F, Clipp S, Dorronsoro M, Gaziano JM, Giovannucci EL, Hankinson SE, Hartge P, Hoover RN, Hunter DJ, Jacobs KB, Jenab M, Kraft P, Kooperberg C, Lynch SM, Sund M, Mendelsohn JB, Mouw T, Newton CC, Overvad K, Palli D, Peeters PH, Rajkovic A, Shu XO, Thomas G, Tobias GS, Trichopoulos D, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu K, Zeleniuch-Jacquotte A. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Int J Cancer 2010;127:1421–1428.

    Article  PubMed  CAS  Google Scholar 

  19. Klein AP, Brune KA, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Griffin C, Cameron JL, Yeo CJ, Kern S, Hruban RH. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res 2004;64:2634–2638.

    Article  PubMed  CAS  Google Scholar 

  20. Tersmette AC, Petersen GM, Offerhaus GJ, Falatko FC, Brune KA, Goggins M, Rozenblum E, Wilentz RE, Yeo CJ, Cameron JL, Kern SE, Hruban RH. Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 2001;7:738–744.

    PubMed  CAS  Google Scholar 

  21. Brand RE, Lerch MM, Rubinstein WS, Neoptolemos JP, Whitcomb DC, Hruban RH, Brentnall TA, Lynch HT, Canto MI; Participants of the Fourth International Symposium of Inherited Diseases of the Pancreas. Advances in counseling and surveillance of patients at risk for pancreatic cancer. Gut 2007;56:1460–1469

    Article  PubMed  Google Scholar 

  22. Eppel A, Cotterchio M, Gallinger S. Allergies are associated with reduced pancreas cancer risk: A population-based case–control study in Ontario, Canada. Int J Cancer 2007;121:2241–2245.

    Article  PubMed  CAS  Google Scholar 

  23. Ghadirian P, Liu G, Gallinger S, Schmocker B, Paradis AJ, Lal G, Brunet JS, Foulkes WD, Narod SA. Risk of pancreatic cancer among individuals with a family history of cancer of the pancreas. Int J Cancer 2002;97:807–810.

    Article  PubMed  CAS  Google Scholar 

  24. Wang W, Chen S, Brune KA, Hruban RH, Parmigiani G, Klein AP. PancPRO: risk assessment for individuals with a family history of pancreatic cancer. J Clin Oncol 2007;25:1417–1422.

    Article  PubMed  Google Scholar 

  25. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) DevCan database: “SEER 17 Incidence and Mortality, 2000–2006, with Kaposi Sarcoma and Mesothelioma”. National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2009, based on the Novermber 2008 submission. Underlying mortality data provided by NCHS (www.cdc.gov/nchs).

  26. Brentnall TA, Bronner MP, Byrd DR, Haggitt RC, Kimmey MB. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 1999;131:247–255.

    PubMed  CAS  Google Scholar 

  27. Langer P, Kann PH, Fendrich V, Habbe N, Schneider M, Sina M, Slater EP, Heverhagen JT, Gress TM, Rothmund M, Bartsch DK. Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut 2009;58:1410–1418.

    Article  PubMed  CAS  Google Scholar 

  28. Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, Fishman EK, Brune K, Axilbund J, Griffin C, Ali S, Richman J, Jagannath S, Kantseoy SV, Kalloo AN. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 2006;4:766–781.

    Article  PubMed  Google Scholar 

  29. Vasen HF, Wasser M, van Mil A, Tollenaar RA, Konstantinovski M, Gruis NA, Bergman W, Hes FJ, Hommes DW, Offerhaus GJ, Morreau H, Bonsing BA, de Vos tot Nederveen Cappel WH. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology 2011;140:850–856.

    Article  PubMed  CAS  Google Scholar 

  30. Verna EC, Hwang C, Stevens PD, Rotterdam H, Stavropoulos SN, Sy CD, Prince MA, Chung WK, Fine RL, Chabot JA, Frucht H. Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res 2010;16:5028–5037.

    Article  PubMed  Google Scholar 

  31. Ludwig E, Olson SH, Bayuga S, Simon J, Schattner MA, Gerdes H, Allen PJ, Jarnagin WR, Kurtz RC. Feasibility and Yield of Screening in Relatives From Familial Pancreatic Cancer Families. Am J Gastroenterol 2011 May;106(5):946–54.

    Article  PubMed  Google Scholar 

  32. Chu D, Kohlmann W, Adler DG. Identification and screening of individuals at increased risk for pancreatic cancer with emphasis on known environmental and genetic factors and hereditary syndromes. JOP 2010;11:203–212.

    PubMed  Google Scholar 

  33. Ku YM, Shin SS, Lee CH, Semelka RC. Magnetic resonance imaging of cystic and endocrine pancreatic neoplasms. Top Magn Reson Imaging 2009;20:11–18.

    Article  PubMed  Google Scholar 

  34. Canto MI, Goggins M, Yeo CJ, Griffin C, Axilbund JE, Brune K, Ali SZ, Jagannath S, Petersen GM, Fishman EK, Piantadosi S, Giardiello FM, Hruban RH. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol 2004;2:606–621.

    Article  PubMed  Google Scholar 

  35. Sipos B, Frank S, Gress T, Hahn S, Kloppel G. Pancreatic intraepithelial neoplasia revisited and updated. Pancreatology 2009;9:45–54.

    Article  PubMed  CAS  Google Scholar 

  36. Poley JW, Kluijt I, Gouma DJ, Harinck F, Wagner A, Aalfs C, van Eijck CH, Cats A, Kuipers EJ, Nio Y, Fockens P, Bruno MJ. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroeneterol 2009;104:2175–2181.

    Article  CAS  Google Scholar 

  37. Reid-Lombardo KM, St Sauver J, Li Z, Ahrens WA, Unni KK, Que FG. Incidence, prevalence, and management of intraductal papillary mucinous neoplasm in Olmsted County, Minnesota, 1984–2005: a population study. Pancreas 2008;37:139–144

    Article  PubMed  Google Scholar 

  38. de Jong K, Nio CY, Hermans JJ, Dijkgraaf MG, Gouma DJ, van Eijck CH, van Heel E, Klass G, Fockens P, Bruno MJ. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenetrol Hepatol 2010;8:806–811.

    Article  Google Scholar 

  39. Tanno S, Nakano Y, Nishikawa T, Nakamura K, Sasajima J, Minoguchi M, Mizukami Y, Yanagawa N, Fujii T, Obara T, Okumura T, Kohgo Y. Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results. Gut 2008;57:339–343.

    Article  PubMed  CAS  Google Scholar 

  40. Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, Iacobuzio-Donahue CA. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 2010;467:1114–1117.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hepatobiliary/Pancreatic Surgical Oncology Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Canada

    Wigdan Al-Sukhni, Robert Grant & Steven Gallinger

  2. Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, University of Toronto, Toronto, Canada

    Ayelet Borgida, Heidi Rothenmund, Spring Holter, Kara Semotiuk & Steven Gallinger

  3. Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada

    Stephanie Wilson, Kartik Jhaveri & Masoom A. Haider

  4. Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada

    Malcolm Moore

  5. Women’s College Research Institute, University of Toronto, Toronto, Canada

    Steven Narod

  6. Toronto General Hospital, 10th Floor Rm 10EN206, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada

    Steven Gallinger

Authors
  1. Wigdan Al-Sukhni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayelet Borgida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heidi Rothenmund
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Spring Holter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kara Semotiuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephanie Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Malcolm Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Steven Narod
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kartik Jhaveri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masoom A. Haider
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Steven Gallinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven Gallinger.

Additional information

Sources of funding

Pancreas Cancer Canada; NIH-PACGENE (Grant # 5R01CA097975-08); Princess Margaret Hospital Foundation Invest-in-Research Fund

Some of the content of this manuscript was presented as a poster at the ASCO (American Society of Clinical Oncology) 2011 meeting in Chicago, Illinois, USA (June 4–8).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al-Sukhni, W., Borgida, A., Rothenmund, H. et al. Screening for Pancreatic Cancer in a High-Risk Cohort: An Eight-Year Experience. J Gastrointest Surg 16, 771–783 (2012). https://doi.org/10.1007/s11605-011-1781-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-011-1781-6

Keywords

Search

Navigation