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Cystic precursors to invasive pancreatic cancer

Abstract

Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not.

Key Points

  • The number of patients being diagnosed with pancreatic cysts is increasing dramatically owing to the widespread use of high resolution imaging modalities

  • Although some pancreatic cysts are benign, others (such as intraductal papillary mucinous neoplasms or mucinous cystic neoplasms) are precursor lesions of invasive pancreatic cancer that might undergo malignant transformation

  • Diagnosis and risk assessment of pancreatic cystic lesions before surgery is challenging, which hampers the implementation of an appropriate therapeutic stratification

  • Ongoing research is trying to discover diagnostic targets to enable a tailor-made approach to the treatment of patients with pancreatic cystic lesions

  • The discovery of biomarkers in pancreatic cyst fluid (a readily available clinical specimen) is believed to provide diagnostic targets for translation into improved clinical management of patients with pancreatic cysts

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Figure 1: Multifocal intraductal papillary mucinous neoplasms (IPMNs) within a pancreas.
Figure 2: Cystic precursor lesions of pancreatic cancer.

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References

  1. Brugge, W. R. et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 126, 1330–1336 (2004).

    Article  PubMed  Google Scholar 

  2. Fernández-del Castillo, C. et al. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch. Surg. 138, 427–434 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Spinelli, K. S. et al. Cystic pancreatic neoplasms: observe or operate. Ann. Surg. 239, 651–659 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Winter, J. M. et al. Periampullary and pancreatic incidentaloma: a single institution's experience with an increasingly common diagnosis. Ann. Surg. 243, 673–683 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114–1117 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tanaka, M. et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 6, 17–32 (2006).

    Article  PubMed  Google Scholar 

  7. Park, W. G. et al. Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts. Pancreas 40, 42–45 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tang, R. S. et al. Evaluation of the guidelines for management of pancreatic branch-duct intraductal papillary mucinous neoplasm. Clin. Gastroenterol. Hepatol. 6, 815–819 (2008).

    Article  PubMed  Google Scholar 

  9. Sawhney, M. S. et al. International consensus guidelines for surgical resection of mucinous neoplasms cannot be applied to all cystic lesions of the pancreas. Clin. Gastroenterol. Hepatol. 7, 1373–1376 (2009).

    Article  PubMed  Google Scholar 

  10. Winter, J. M. et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J. Gastrointest. Surg. 10, 1199–1211 (2006).

    Article  PubMed  Google Scholar 

  11. Ikeda, M. et al. Morphologic changes in the pancreas detected by screening ultrasonography in a mass survey, with special reference to main duct dilatation, cyst formation, and calcification. Pancreas 9, 508–512 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, X. M., Mitchell, D. G., Dohke, M., Holland, G. A. & Parker, L. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology 223, 547–553 (2002).

    Article  PubMed  Google Scholar 

  13. Lee, K. S., Sekhar, A., Rofsky, N. M. & Pedrosa, I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am. J. Gastroenterol. 105, 2079–2084 (2010).

    Article  PubMed  Google Scholar 

  14. Laffan, T. A. et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am. J. Roentgenol. 191, 802–807 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kimura, W., Nagai, H., Kuroda, A., Muto, T. & Esaki, Y. Analysis of small cystic lesions of the pancreas. Int. J. Pancreatol. 18, 197–206 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Ohhashi, K., Murakami, F. & Maruyama, M. Four cases of mucous secreting pancreatic cancer. Prog. Dig. Endosc. 203, 348–351 (1982).

    Google Scholar 

  17. Belyaev, O. et al. Intraductal papillary mucinous neoplasms of the pancreas. J. Clin. Gastroenterol. 42, 284–294 (2008).

    Article  PubMed  Google Scholar 

  18. Bassi, C., Sarr, M. G., Lillemoe, K. D. & Reber, H. A. Natural history of intraductal papillary mucinous neoplasms (IPMN): current evidence and implications for management. J. Gastrointest. Surg. 12, 645–650 (2008).

    Article  PubMed  Google Scholar 

  19. Tanaka, M., Kobayashi, K., Mizumoto, K. & Yamaguchi, K. Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas. J. Gastroenterol. 40, 669–675 (2005).

    Article  PubMed  Google Scholar 

  20. Schmidt, C. M. et al. Intraductal papillary mucinous neoplasms: predictors of malignant and invasive pathology. Ann. Surg. 246, 644–651 (2007).

    Article  PubMed  Google Scholar 

  21. Furukawa, T. et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 447, 794–799 (2005).

    Article  PubMed  Google Scholar 

  22. Yonezawa, S., Nakamura, A., Horinouchi, M. & Sato, E. The expression of several types of mucin is related to the biological behavior of pancreatic neoplasms. J. Hepatobiliary Pancreat. Surg. 9, 328–341 (2002).

    Article  PubMed  Google Scholar 

  23. Moriya, T. et al. Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms. Int. J. Gastrointest. Cancer 35, 111–119 (2005).

    Article  PubMed  Google Scholar 

  24. Adsay, N. V. et al. Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs: coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas. Am. J. Surg. Pathol. 27, 571–578 (2003).

    Article  PubMed  Google Scholar 

  25. Adsay, N. V. et al. Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an “intestinal” pathway of carcinogenesis in the pancreas. Am. J. Surg. Pathol. 28, 839–848 (2004).

    Article  PubMed  Google Scholar 

  26. Salvia, R. et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann. Surg. 239, 678–687 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tollefson, M. K. et al. Intraductal papillary mucinous neoplasm: did it exist prior to 1980? Pancreas 26, e55–e58 (2003).

    Article  PubMed  Google Scholar 

  28. Ferrone, C. R. et al. Current trends in pancreatic cystic neoplasms. Arch. Surg. 144, 448–454 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sohn, T. A. et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann. Surg. 239, 788–799 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sato, N. et al. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am. J. Pathol. 159, 2017–2022 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chetty, R. et al. Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis. Hum. Pathol. 37, 212–217 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Brune, K. et al. Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am. J. Surg. Pathol. 30, 1067–1076 (2006).

    PubMed  PubMed Central  Google Scholar 

  33. Fernández-del Castillo, C., Alsfasser, G., Targarona, J., Brugge, W. R. & Warshaw, A. L. Serum CA 19–9 in the management of cystic lesions of the pancreas. Pancreas 32, 220 (2006).

    PubMed  Google Scholar 

  34. Bosman, F. T., Carneiro, F., Hruban, R. & Theise, N. WHO Classification of Tumours of the Digestive System (World Health Organization, Lyon, 2010).

    Google Scholar 

  35. Adsay, N. V. et al. Colloid (mucinous noncystic) carcinoma of the pancreas. Am. J. Surg. Pathol. 25, 26–42 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Crippa, S. et al. Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiological characteristics. Clin. Gastroenterol. Hepatol. 8, 213–219 (2010).

    Article  PubMed  Google Scholar 

  37. Rodriguez, J. R. et al. Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection. Gastroenterology 133, 72–79 (2007).

    Article  PubMed  Google Scholar 

  38. Salvia, R. et al. Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate? Gut 56, 1086–1090 (2007).

    Article  PubMed  Google Scholar 

  39. Chari, S. T. et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology 123, 1500–1507 (2002).

    Article  PubMed  Google Scholar 

  40. Kobayashi, G. et al. Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS. J. Gastroenterol. 40, 744–751 (2005).

    Article  PubMed  Google Scholar 

  41. Salvia, R. et al. Intraductal papillary mucinous neoplasms of the pancreas with multifocal involvement of branch ducts. Am. J. Surg. 198, 709–714 (2009).

    Article  PubMed  Google Scholar 

  42. Reid-Lombardo, K. M., Mathis, K. L., Wood, C. M., Harmsen, W. S. & Sarr, M. G. Frequency of extrapancreatic neoplasms in intraductal papillary mucinous neoplasm of the pancreas: implications for management. Ann. Surg. 251, 64–69 (2010).

    Article  PubMed  Google Scholar 

  43. Fritz, S. et al. Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma. Ann. Surg. 249, 440–447 (2009).

    Article  PubMed  Google Scholar 

  44. Schönleben, F. et al. BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas. Cancer Lett. 249, 242–248 (2007).

    Article  PubMed  CAS  Google Scholar 

  45. Iacobuzio-Donahue, C. A. et al. Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal adenocarcinomas. Am. J. Pathol. 157, 755–761 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sahin, F. et al. Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms. Mod. Pathol. 16, 686–691 (2003).

    Article  PubMed  Google Scholar 

  47. Schönleben, F. et al. PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin. Cancer Res. 12, 3851–3855 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Sato, N. et al. Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas. Am. J. Pathol. 164, 903–914 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cubilla, A. L. & Fitzgerald, P. J. Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res. 36, 2690–2698 (1976).

    CAS  PubMed  Google Scholar 

  50. Klimstra, D. S. Cystic, mucin-producing neoplasms of the pancreas: the distinguishing features of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Semin. Diagn. Pathol. 22, 318–329 (2005).

    Article  PubMed  Google Scholar 

  51. Crippa, S. et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann. Surg. 247, 571–579 (2008).

    Article  PubMed  Google Scholar 

  52. Buscaglia, J. M. et al. Patient- and cyst-related factors for improved prediction of malignancy within cystic lesions of the pancreas. Pancreatology 9, 631–638 (2009).

    Article  PubMed  Google Scholar 

  53. Garcea, G. et al. Cystic lesions of the pancreas. A diagnostic and management dilemma. Pancreatology 8, 236–251 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Fernández-del Castillo, C. Mucinous cystic neoplasms. J. Gastrointest. Surg. 12, 411–413 (2008).

    Article  PubMed  Google Scholar 

  55. Wilentz, R. E., Albores-Saavedra, J. & Hruban, R. H. Mucinous cystic neoplasms of the pancreas. Semin. Diagn. Pathol. 17, 31–42 (2000).

    CAS  PubMed  Google Scholar 

  56. Wilentz, R. E. et al. Pathologic examination accurately predicts prognosis in mucinous cystic neoplasms of the pancreas. Am. J. Surg. Pathol. 23, 1320–1327 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Yamao, K. et al. Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan pancreas society. Pancreas 40, 67–71 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. Jimenez, R. E. et al. Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy. Ann. Surg. 230, 501–511 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Iacobuzio-Donahue, C. A. et al. Dpc4 protein in mucinous cystic neoplasms of the pancreas: frequent loss of expression in invasive carcinomas suggests a role in genetic progression. Am. J. Surg. Pathol. 24, 1544–1548 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Lüttges, J., Feyerabend, B., Buchelt, T., Pacena, M. & Klöppel, G. The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. Am. J. Surg. Pathol. 26, 466–471 (2002).

    Article  PubMed  Google Scholar 

  61. Fukushima, N. et al. Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays. Oncogene 23, 9042–9051 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Ornitz, D. M., Hammer, R. E., Messing, A., Palmiter, R. D. & Brinster, R. L. Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 238, 188–193 (1987).

    Article  CAS  PubMed  Google Scholar 

  63. Quaife, C. J., Pinkert, C. A., Ornitz, D. M., Palmiter, R. D. & Brinster, R. L. Pancreatic neoplasia induced by ras expression in acinar cells of transgenic mice. Cell 48, 1023–1034 (1987).

    Article  CAS  PubMed  Google Scholar 

  64. Hruban, R. H. et al. Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations. Cancer Res. 66, 95–106 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 4, 437–450 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Hingorani, S. R. et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 7, 469–483 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Bardeesy, N. et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc. Natl Acad. Sci. USA 103, 5947–5952 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pasca di Magliano, M. et al. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev. 20, 3161–3173 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Siveke, J. T. et al. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 12, 266–279 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Kojima, K. et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 67, 8121–8130 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Bardeesy, N. et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 20, 3130–3146 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Izeradjene, K. et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell. 11, 229–243 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Kamiyama, H. et al. In vivo and in vitro propagation of intraductal papillary mucinous neoplasms. Lab. Invest. 90, 665–673 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Sorio, C. et al. Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion. Virchows Arch. 446, 239–245 (2005).

    Article  PubMed  Google Scholar 

  75. Brugge, W. R., Lauwers, G. Y., Sahani, D., Fernández-del Castillo, C. & Warshaw, A. L. Cystic neoplasms of the pancreas. N. Engl. J. Med. 351, 1218–1226 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Walsh, R. M. et al. Prospective preoperative determination of mucinous pancreatic cystic neoplasms. Surgery 132, 628–634 (2002).

    Article  PubMed  Google Scholar 

  77. Lewandrowski, K. B., Southern, J. F., Pins, M. R., Compton, C. C. & Warshaw, A. L. Cyst fluid analysis in the differential diagnosis of pancreatic cysts. A comparison of pseudocysts, serous cystadenomas, mucinous cystic neoplasms, and mucinous cystadenocarcinoma. Ann. Surg. 217, 41–47 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Allen, P. J. et al. Pancreatic cyst fluid protein expression profiling for discriminating between serous cystadenoma and intraductal papillary mucinous neoplasm. Ann. Surg. 250, 754–760 (2009).

    Article  PubMed  Google Scholar 

  79. Nagula, S. et al. Evaluation of cyst fluid CEA analysis in the diagnosis of mucinous cysts of the pancreas. J. Gastrointest. Surg. 14, 1997–2003 (2010).

    Article  PubMed  Google Scholar 

  80. Raval, J. S. et al. Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis. Mod. Pathol. 23, 1467–1476 (2010).

    Article  CAS  PubMed  Google Scholar 

  81. Pelaez-Luna, M. & Chari, S. T. Cyst fluid analysis to diagnose pancreatic cystic lesions: an as yet unfulfilled promise. Gastroenterology 130, 1007–1009 (2006).

    Article  PubMed  Google Scholar 

  82. van der Waaij, L. A., van Dullemen, H. M. & Porte, R. J. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest. Endosc. 62, 383–389 (2005).

    Article  PubMed  Google Scholar 

  83. Khalid, A. et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Clin. Gastroenterol. Hepatol. 3, 967–973 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. Schoedel, K. E., Finkelstein, S. D. & Ohori, N. P. K-Ras and microsatellite marker analysis of fine-needle aspirates from intraductal papillary mucinous neoplasms of the pancreas. Diagn. Cytopathol. 34, 605–608 (2006).

    Article  PubMed  Google Scholar 

  85. Khalid, A. et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest. Endosc. 69, 1095–1102 (2009).

    Article  PubMed  Google Scholar 

  86. Anderson, M. A., Kwon, R. S. & Scheiman, J. M. PANDA cyst-fluid analysis: eats, shoots and leaves? Gastrointest. Endosc. 69, 1103–1105 (2009).

    Article  PubMed  Google Scholar 

  87. Polkowski, M. Endoscopic ultrasonography. Endoscopy 42, 68–72 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Habbe, N. et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol. Ther. 8, 340–346 (2009).

    Article  CAS  PubMed  Google Scholar 

  89. Hong, S. M. et al. Multiple genes are hypermethylated in intraductal papillary mucinous neoplasms of the pancreas. Mod. Pathol. 21, 1499–1507 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Croce, C. M. & Calin, G. A. miRNAs, cancer, and stem cell division. Cell 122, 6–7 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Szafranska, A. E. et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene 26, 4442–4452 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Lee, E. J. et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int. J. Cancer 120, 1046–1054 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bloomston, M. et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 297, 1901–1908 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Pelaez-Luna, M. et al. Do consensus indications for resection in branch duct intraductal papillary mucinous neoplasm predict malignancy? A study of 147 patients. 102, 1759–1764 (2007).

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Acknowledgements

The authors wish to thank Dr Karen M. Horton (Johns Hopkins University) for the CT scan of multifocal IPMN used in Figure 1. The authors would like to acknowledge the support of grants P50CA062924 and R01CA113669 (A. Maitra) and a research fellowship grant from Deutsche Krebshilfe, Bonn, Germany (H. Matthaei), the Sol Goldman Pancreatic Cancer Research Center and the Michael Rolfe Foundation for Pancreatic Cancer Research.C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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Correspondence to Anirban Maitra.

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Matthaei, H., Schulick, R., Hruban, R. et al. Cystic precursors to invasive pancreatic cancer. Nat Rev Gastroenterol Hepatol 8, 141–150 (2011). https://doi.org/10.1038/nrgastro.2011.2

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