Advertisement

Pancreatic Cancer pp 1401-1434 | Cite as

Secondary Screening for Inherited Pancreatic Ductal Adenocarcinoma

  • Andrea Sheel
  • James Nicholson
  • Ioannis Sarantitis
  • John P. Neoptolemos
  • William Greenhalf
Reference work entry

Abstract

The prevalence of pancreatic cancer is too low, and the accuracy of current screening methods is not high enough to permit general population screening. Secondary screening in high-risk groups may be possible for the disease or its precursors. Pilot screening studies have been initiated and are generating data on the nature of inherited predisposition and the early stages of cancer development. It is already apparent that the specificity and sensitivity of secondary screening tests need to be improved. In this chapter, the preliminary evidence from the pioneering screening studies will be considered in order to discuss which participants should be recruited into future pilot studies and how biomarkers may in future be combined with imaging to reduce the number of missed cancers and premature surgical interventions.

Keywords

Pancreatic cancer Inherited diseases Risk Screening 

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Rahib L, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Mancuso A, Calabro F, Sternberg CN. Current therapies and advances in the treatment of pancreatic cancer. Crit Rev Oncol Hematol. 2006;58(3):231–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223(3):273–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Sirri E, et al. Recent trends in survival of patients with pancreatic cancer in Germany and the United States. Pancreas. 2016;45(6):908–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Neoptolemos JP, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24.CrossRefPubMedGoogle Scholar
  7. 7.
    Winter JM, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10(9):1199–210. discussion 1210-1CrossRefPubMedGoogle Scholar
  8. 8.
    Helmstaedter L, Riemann JF. Pancreatic cancer-EUS and early diagnosis. Langenbecks Arch Surg. 2008;393(6):923–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Poruk KE, et al. Screening for pancreatic cancer: why, how, and who? Ann Surg. 2013;257(1):17–26.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Luo J, et al. Interpreting trends of pancreatic cancer incidence and mortality: a nation-wide study in Sweden (1960-2003). Cancer Causes Control. 2008;19(1):89–96.PubMedCrossRefGoogle Scholar
  11. 11.
    Alexakis N, et al. Current standards of surgery for pancreatic cancer. Br J Surg. 2004;91(11):1410–27.PubMedCrossRefGoogle Scholar
  12. 12.
    Brand RE, et al. Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut. 2007;56(10):1460–9.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339–47.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Klein AP, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64(7):2634–8.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Howes N, et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol. 2004;2(3):252–61.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Algul H, et al. Mechanisms of disease: chronic inflammation and cancer in the pancreas – a potential role for pancreatic stellate cells? Nat Clin Pract Gastroenterol Hepatol. 2007;4(8):454–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Latchford A, et al. Peutz-Jeghers syndrome and screening for pancreatic cancer. Br J Surg. 2006;93(12):1446–55.PubMedCrossRefGoogle Scholar
  18. 18.
    Giardiello FM, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119(6):1447–53.PubMedCrossRefGoogle Scholar
  19. 19.
    Hahn SA, et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst. 2003;95(3):214–21.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    van Asperen CJ, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005;42(9):711–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Pandharipande PV, et al. Targeted screening of individuals at high risk for pancreatic cancer: results of a simulation model. Radiology. 2015;275(1):177–87.PubMedCrossRefGoogle Scholar
  22. 22.
    Schutte M, et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997;57(15):3126–30.PubMedGoogle Scholar
  23. 23.
    Vasen HF, et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000;87(6):809–11.PubMedCrossRefGoogle Scholar
  24. 24.
    Al-Sukhni W, et al. Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. Hum Genet. 2008;Google Scholar
  25. 25.
    Roberts NJ, et al. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov. 2016;6(2):166–75.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Tersmette AC, et al. Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res. 2001;7:738–44.PubMedGoogle Scholar
  27. 27.
    Del Chiaro M, et al. Cancer risk among the relatives of patients with pancreatic ductal adenocarcinoma. Pancreatology. 2007;7(5–6):459–69.PubMedGoogle Scholar
  28. 28.
    Greenhalf W, Vitone LJ, Neoptolemos J. Familial pancreatic cancer. In: Beger H-G, et al., editors. The pancreas: an integrated textbook of basic science, medicine and surgery. Oxford: Blackwell; 2008. p. 591–600.CrossRefGoogle Scholar
  29. 29.
    McFaul C, et al. Anticipation in familial pancreatic cancer. Gut. 2006;55(2):252–8.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Ekbom A, Hunter D. Pancreatic cancer. In: Adami H, Hunter D, Trichopoulos D, editors. Textbook of cancer epidemiology. New York: Oxford University Press; 2002. p. 233–47.Google Scholar
  31. 31.
    Silverman DT, et al. Cigarette smoking and pancreas cancer: a case-control study based on direct interviews. J Natl Cancer Inst. 1994;86(20):1510–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Fuchs CS, et al. A prospective study of cigarette smoking and the risk of pancreatic cancer. Arch Intern Med. 1996;156(19):2255–60.PubMedCrossRefGoogle Scholar
  33. 33.
    Hassan MM, et al. Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol. 2007;102(12):2696–707.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Rulyak SJ, et al. Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds. Gastroenterology. 2003;124(5):1292–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Rebours V, et al. Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series. Am J Gastroenterol. 2008;103(1):111–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Chen J, et al. Polymorphisms of p21 and p27 jointly contribute to an earlier age at diagnosis of pancreatic cancer. Cancer Lett. 2008;Google Scholar
  37. 37.
    Wang W, et al. PancPRO: risk assessment for individuals with a family history of pancreatic cancer. J Clin Oncol. 2007;25(11):1417–22.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Jones R, et al. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database. BMJ. 2007;334(7602):1040.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Greenhalf W, Neoptolemos JP. Increasing survival rates of patients with pancreatic cancer by earlier identification. Nat Clin Pract Oncol. 2006;3(7):346–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Chari ST, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology. 2008;134(1):95–101.PubMedCrossRefGoogle Scholar
  41. 41.
    Pannala R, et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134(4):981–7.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Fernandez E, et al. Family history and the risk of liver, gallbladder, and pancreatic cancer. Cancer Epidemiol Biomark Prev. 1994;3:209–12.Google Scholar
  43. 43.
    Canto MI, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012;142(4):796–804.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Kalra MK, et al. State-of-the-art imaging of pancreatic neoplasms. Br J Radiol. 2003;76(912):857–65.PubMedCrossRefGoogle Scholar
  45. 45.
    Hanada K, et al. Effective screening for early diagnosis of pancreatic cancer. Best Pract Res Clin Gastroenterol. 2015;29(6):929–39.PubMedCrossRefGoogle Scholar
  46. 46.
    Hruban RH, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28(8):977–87.CrossRefPubMedGoogle Scholar
  47. 47.
    Canto MI, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2(7):606–21.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen J, et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a systematic review. J Cancer Res Clin Oncol. 2012;138(9):1433–41.PubMedCrossRefGoogle Scholar
  49. 49.
    Puli SR, et al. How good is endoscopic ultrasound-guided fine-needle aspiration in diagnosing the correct etiology for a solid pancreatic mass?: a meta-analysis and systematic review. Pancreas. 2013;42(1):20–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Barthet M, et al. Endoscopic ultrasonographic diagnosis of pancreatic cancer complicating chronic pancreatitis. Endoscopy. 1996;28(6):487–91.PubMedCrossRefGoogle Scholar
  51. 51.
    Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc. 2005;62(5):728–36. quiz 751, 753PubMedCrossRefGoogle Scholar
  52. 52.
    Gangi S, et al. Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis. AJR Am J Roentgenol. 2004;182(4):897–903.PubMedCrossRefGoogle Scholar
  53. 53.
    Saisho H, Yamaguchi T. Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography. Pancreas. 2004;28(3):273–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Semelka RC, et al. Imaging strategies to reduce the risk of radiation in CT studies, including selective substitution with MRI. J Magn Reson Imaging. 2007;25(5):900–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Diehl SJ, et al. MR imaging of pancreatic lesions. Comparison of manganese-DPDP and gadolinium chelate. Invest Radiol. 1999;34(9):589–95.PubMedCrossRefGoogle Scholar
  56. 56.
    Del Chiaro M, et al. Short-term results of a magnetic resonance imaging-based swedish screening program for individuals at risk for pancreatic cancer. JAMA Surg. 2015;150(6):512–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Harinck F, et al. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut. 2016;65(9):1505–13.PubMedCrossRefGoogle Scholar
  58. 58.
    Bartsch DK, et al. Refinement of screening for familial pancreatic cancer. Gut. 2016;65(8):1314–21.PubMedCrossRefGoogle Scholar
  59. 59.
    Matsumoto I, et al. 18-Fluorodeoxyglucose positron emission tomography does not aid in diagnosis of pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2013;11(6):712–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Baiocchi GL, et al. Possible additional value of 18FDG-PET in managing pancreas intraductal papillary mucinous neoplasms: preliminary results. J Exp Clin Cancer Res. 2008;27:10.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Yan L, et al. Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups. Gastroenterology. 2005;128(7):2124–30.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Nicholson JA, et al. Incidence of post-ERCP pancreatitis from direct pancreatic juice collection in hereditary pancreatitis and familial pancreatic cancer before and after the introduction of prophylactic pancreatic stents and rectal diclofenac. Pancreas. 2015;44(2):260–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Eshleman JR, et al. KRAS and guanine nucleotide-binding protein mutations in pancreatic juice collected from the duodenum of patients at high risk for neoplasia undergoing endoscopic ultrasound. Clin Gastroenterol Hepatol. 2015;13(5):963–9. e4PubMedCrossRefGoogle Scholar
  64. 64.
    Suenaga M, et al. Using an endoscopic distal cap to collect pancreatic fluid from the ampulla (with video). Gastrointest Endosc. 2017.PubMedCrossRefGoogle Scholar
  65. 65.
    Vasen H, et al. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers. J Clin Oncol. 2016;34(17):2010–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Ben Q, et al. The relationship between new-onset diabetes mellitus and pancreatic cancer risk: a case-control study. Eur J Cancer. 2011;47(2):248–54.PubMedCrossRefGoogle Scholar
  67. 67.
    Aggarwal G, et al. Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in beta cells and mice. Gastroenterology. 2012;143(6):1510–7. e1PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Sah RP, et al. New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol. 2013;10(7):423–33.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Boursi B, et al. A clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes. Gastroenterology. 2017;152(4):840–50. e3PubMedCrossRefGoogle Scholar
  70. 70.
    Locker GY, et al. ASCO 2006 Update of recommendations for the use of Tumor Markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–27.PubMedCrossRefGoogle Scholar
  71. 71.
    Wong D, et al. Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas. 2008;37(3):269–74.PubMedCrossRefGoogle Scholar
  72. 72.
    Marrelli D, et al. CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg. 2009;198(3):333–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Kim JE, et al. Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol. 2004;19(2):182–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Jenkinson C, et al. Decreased serum thrombospondin-1 levels in pancreatic cancer patients up to 24 months prior to clinical diagnosis: association with diabetes mellitus. Clin Cancer Res. 2015;Google Scholar
  75. 75.
    Miyazono F, et al. Molecular detection of circulating cancer cells during surgery in patients with biliary-pancreatic cancer. Am J Surg. 1999;177(6):475–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Kurihara T, et al. Detection of circulating tumor cells in patients with pancreatic cancer: a preliminary result. J Hepato-Biliary-Pancreat Surg. 2008;15(2):189–95.CrossRefGoogle Scholar
  77. 77.
    Rhim AD, et al. EMT and dissemination precede pancreatic tumor formation. Cell. 2012;148(1–2):349–61.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Gorges TM, et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Khoja L, et al. A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker. Br J Cancer. 2012;106(3):508–16.CrossRefPubMedGoogle Scholar
  80. 80.
    Rhim AD, et al. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology. 2014;146(3):647–51.CrossRefPubMedGoogle Scholar
  81. 81.
    Thege FI, et al. Microfluidic immunocapture of circulating pancreatic cells using parallel EpCAM and MUC1 capture: characterization, optimization and downstream analysis. Lab Chip. 2014;14(10):1775–84.CrossRefPubMedGoogle Scholar
  82. 82.
    Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem. 2015;61(1):112–23.PubMedCrossRefGoogle Scholar
  83. 83.
    Olsson E, et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med. 2015;7(8):1034–47.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Tabernero J, et al. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Lancet Oncol. 2015;16(8):937–48.PubMedCrossRefGoogle Scholar
  85. 85.
    Bagul A, et al. Quantitative analysis of plasma DNA in severe acute pancreatitis. JOP. 2006;7(6):602–7.PubMedGoogle Scholar
  86. 86.
    Holdenrieder S, et al. Nucleosomes in serum of patients with benign and malignant diseases. Int J Cancer. 2001;95(2):114–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Holdenrieder S, et al. Clinical relevance of circulating nucleosomes in cancer. Ann N Y Acad Sci. 2008;1137:180–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Magistrelli P, et al. K-ras mutations in circulating DNA from pancreatic and lung cancers: bridging methodology for a common validation of the molecular diagnosis value. Pancreas. 2008;37(1):101–2.PubMedCrossRefGoogle Scholar
  89. 89.
    Thompson JC, et al. Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next-generation sequencing of cell-free circulating tumor DNA. Clin Cancer Res. 2016;22(23):5772–82.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Chen Z, et al. Enhanced sensitivity for detection of low-level germline mosaic RB1 mutations in sporadic retinoblastoma cases using deep semiconductor sequencing. Hum Mutat. 2014;35(3):384–91.PubMedCrossRefGoogle Scholar
  91. 91.
    Yu J, et al. Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms. Gut. 2016.Google Scholar
  92. 92.
    Pugliese V, et al. Pancreatic intraductal sampling during ERCP in patients with chronic pancreatitis and pancreatic cancer: cytologic studies and k-ras-2 codon 12 molecular analysis in 47 cases. Gastrointest Endosc. 2001;104(5):2830–6.Google Scholar
  93. 93.
    Yamaguchi T, et al. Pancreatic juice cytology in the diagnosis of intraductal papillary mucinous neoplasm of the pancreas: significance of sampling by peroral pancreatoscopy. Cancer. 2005;104(12):2830–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Li D, et al. Pancreatic cancer. Lancet. 2004;363(9414):1049–57.PubMedCrossRefGoogle Scholar
  95. 95.
    Almoguera C, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53(4):549–54.CrossRefPubMedGoogle Scholar
  96. 96.
    Kawesha A, et al. K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma. Int J Cancer. 2000;89(6):469–74.PubMedCrossRefGoogle Scholar
  97. 97.
    Sho S, et al. Digital PCR improves mutation analysis in pancreas fine needle aspiration biopsy specimens. PLoS One. 2017;12(1):e0170897.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Maire F, et al. Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA. Br J Cancer. 2002;87(5):551–4.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Trumper L, et al. Low sensitivity of the ki-ras polymerase chain reaction for diagnosing pancreatic cancer from pancreatic juice and bile: a multicenter prospective trial. J Clin Oncol. 2002;20(21):4331–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Wilentz RE, et al. K-ras mutations in the duodenal fluid of patients with pancreatic carcinoma. Cancer. 1998;82:96–103.PubMedCrossRefGoogle Scholar
  101. 101.
    Van Laethem JL, et al. Detection of c-Ki-ras gene codon 12 mutations from pancreatic duct brushings in the diagnosis of pancreatic tumours. Gut. 1995;36:781–7.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Lu X, et al. Detecting K-ras and p53 gene mutation from stool and pancreatic juice for diagnosis of early pancreatic cancer. Chin Med J. 2002;115(11):1632–6.PubMedGoogle Scholar
  103. 103.
    Haug U, et al. Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA: high prevalence in a large sample of older adults. Clin Chem. 2007;53(4):787–90.PubMedCrossRefGoogle Scholar
  104. 104.
    Costentin L, et al. Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases. Pancreatology. 2002;2(1):17–25.PubMedCrossRefGoogle Scholar
  105. 105.
    Hodgson DR, et al. ARMS allele-specific amplification-based detection of mutant p53 DNA and mRNA in tumors of the breast. Clin Chem. 2001;47(4):774–8.PubMedGoogle Scholar
  106. 106.
    Kahlert C, et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem. 2014;289(7):3869–75.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Gansauge S, et al. Genetic alterations in chronic pancreatitis: evidence for early occurrence of p53 but not K-ras mutations. Br J Surg. 1998;85:337–40.PubMedCrossRefGoogle Scholar
  108. 108.
    Kanda M, et al. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol. 2013;11(6):719–30. e5CrossRefPubMedGoogle Scholar
  109. 109.
    Dauksa A, et al. Whole blood DNA aberrant methylation in pancreatic adenocarcinoma shows association with the course of the disease: a pilot study. PLoS One. 2012;7(5):e37509.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Kisiel JB, et al. New DNA methylation markers for pancreatic cancer: discovery, tissue validation, and pilot testing in pancreatic juice. Clin Cancer Res. 2015;21(19):4473–81.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Wang Y, et al. Detection of p53 gene mutations in the supernatant of pancreatic juice and plasma from patients with pancreatic carcinomas. Pancreas. 2004;28(1):13–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Yamaguchi Y, et al. Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation. Clin Cancer Res. 1999;5:1147–53.PubMedGoogle Scholar
  113. 113.
    Breitkopf CR, et al. Factors influencing receptivity to future screening options for pancreatic cancer in those with and without pancreatic cancer family history. Hered Cancer Clin Pract. 2012;10(1):8.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Canto MI, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol. 2006;4(6):766–81. quiz 665PubMedCrossRefGoogle Scholar
  115. 115.
    Carlson C, Greenhalf W, Brentnall TA. Screening of hereditary pancreatic cancer families. In: Beger H-G, et al., editors. The pancreas: an integrated textbook of basic science, medicine and surgery. Malden: Blackwell; 2008.Google Scholar
  116. 116.
    Langer P, et al. Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut. 2009;58(10):1410–8.CrossRefPubMedGoogle Scholar
  117. 117.
    Schneider R, et al. German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Familial Cancer. 2011;10(2):323–30.PubMedCrossRefGoogle Scholar
  118. 118.
    Mocci E, et al. PanGen-Fam: Spanish registry of hereditary pancreatic cancer. Eur J Cancer. 2015;51(14):1911–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Joergensen M.T, et al. Is screening for pancreatic cancer in high-risk groups cost-effective? – experience from a Danish national screening program. Pancreatology. 2016.Google Scholar
  120. 120.
    Vasen HF, et al. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology. 2011;140(3):850–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Brentnall TA, et al. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med. 1999;131(4):247–55.PubMedCrossRefGoogle Scholar
  122. 122.
    Kimmey MB, et al. Screening and surveillance for hereditary pancreatic cancer. Gastrointest Endosc. 2002;56(4 Suppl):S82–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Poley JW, et al. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol. 2009;104(9):2175–81.PubMedCrossRefGoogle Scholar
  124. 124.
    Verna EC, et al. Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res. 2010;16(20):5028–37.PubMedCrossRefGoogle Scholar
  125. 125.
    Ludwig E, et al. Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol. 2011;106(5):946–54.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Zubarik R, et al. Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study. Gastrointest Endosc. 2011;74(1):87–95.PubMedCrossRefGoogle Scholar
  127. 127.
    Al-Sukhni W, et al. Screening for pancreatic cancer in a high-risk cohort: an eight-year experience. J Gastrointest Surg. 2012;16(4):771–83.PubMedCrossRefGoogle Scholar
  128. 128.
    Potjer TP, et al. Variation in precursor lesions of pancreatic cancer among high-risk groups. Clin Cancer Res. 2013;19(2):442–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Sud A, et al. Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound. Pancreas. 2014;43(3):458–61.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andrea Sheel
    • 1
  • James Nicholson
    • 1
  • Ioannis Sarantitis
    • 1
  • John P. Neoptolemos
    • 2
  • William Greenhalf
    • 3
  1. 1.Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpoolUK
  2. 2.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany
  3. 3.Department of Molecular and Clinical Cancer MedicineInstitute of Translational Medicine, University of LiverpoolLiverpoolUK

Personalised recommendations