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Pancreatic Cancer

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International Manual of Oncology Practice

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Abstract

Pancreatic cancer most commonly refers to the carcinoma of the exocrine pancreas, a disease that presents a constant challenge in modern oncology, since it is characterized by significant morbidity and carries a uniformly ominous prognosis. Adenocarcinoma of the pancreas is largely perceived as inherently resistant to most of the currently available treatment options, hence needing a Multidisciplinary team (MDT) discussion to face the hydra that might defy easy solutions. Potentially resectable disease might necessitate a more aggressive multimodality approach as early stage detection makes cure plausible. Patients in the advanced and metastatic setting, however, do not share the opportunity to bask in a treatment with curative intent and palliation is the primary aim. Cumulative rise in knowledge of cellular and molecular biology and emerging evidence for the efficacy of new agents promise more potent treatment options and eligible patients with advanced disease are urged to participate in clinical trials. In this chapter, we sought to summarize existing knowledge about pancreatic cancer and present novel and future therapeutic strategies.

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References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  2. Lyratzopoulos G, Abel GA, McPhail S, Neal RD, Rubin GP (2013) Measures of promptness of cancer diagnosis in primary care: secondary analysis of national audit data on patients with 18 common and rarer cancers. Br J Cancer 108:686–690

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Antoniou G, Kountourakis P, Papadimitriou K, Vassiliou V, Papamichael D (2014) Adjuvant therapy for resectable pancreatic adenocarcinoma: review of the current treatment approaches and future directions. Cancer Treat Rev 40:78–85

    Article  PubMed  CAS  Google Scholar 

  4. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F GLOBOCAN 2012. IARC, France

    Google Scholar 

  5. Bray F, Ren JS, Masuyer E, Ferlay J (2013) Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 132:1133–1145

    Article  PubMed  CAS  Google Scholar 

  6. Ma J, Siegel R, Jemal A (2013) Pancreatic cancer death rates by race among US men and women, 1970–2009. J Natl Cancer Inst 105:1694–1700

    Article  PubMed  Google Scholar 

  7. Coupland VH, Kocher HM, Berry DP et al (2012) Incidence and survival for hepatic, pancreatic and biliary cancers in England between 1998 and 2007. Cancer Epidemiol 36:e207–e214

    Article  PubMed  Google Scholar 

  8. Batty GD, Kivimaki M, Morrison D et al (2009) Risk factors for pancreatic cancer mortality: extended follow-up of the original Whitehall Study. Cancer Epidemiol Biomarkers Prev 18:673–675

    Article  PubMed Central  PubMed  Google Scholar 

  9. Bosetti C, Lucenteforte E, Silverman DT et al (2012) Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 23:1880–1888

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Maisonneuve P, Lowenfels AB (2010) Epidemiology of pancreatic cancer: an update. Dig Dis 28:645–656

    Article  PubMed  Google Scholar 

  11. Leenders M, Chuang SC, Dahm CC et al (2012) Plasma cotinine levels and pancreatic cancer in the EPIC cohort study. Int J Cancer 131:997–1002

    Article  PubMed  CAS  Google Scholar 

  12. Bittoni A, Santoni M, Lanese A et al (2014) Neoadjuvant therapy in pancreatic cancer: an emerging strategy. Gastroenterol Res Pract 2014:183852

    Article  PubMed Central  PubMed  Google Scholar 

  13. Anderson MA, Zolotarevsky E, Cooper KL et al (2012) Alcohol and tobacco lower the age of presentation in sporadic pancreatic cancer in a dose-dependent manner: a multicenter study. Am J Gastroenterol 107:1730–1739

    Article  PubMed Central  PubMed  Google Scholar 

  14. Vrieling A, Bueno-de-Mesquita HB, Boshuizen HC et al (2010) Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 126:2394–2403

    PubMed  CAS  Google Scholar 

  15. Chuang SC, Gallo V, Michaud D et al (2011) Exposure to environmental tobacco smoke in childhood and incidence of cancer in adulthood in never smokers in the European Prospective Investigation into Cancer and Nutrition. Cancer Causes Control 22:487–494

    Article  PubMed  Google Scholar 

  16. Cogliano VJ, Baan R, Straif K et al (2011) Preventable exposures associated with human cancers. J Natl Cancer Inst 103:1827–1839

    Article  PubMed Central  PubMed  Google Scholar 

  17. Lucenteforte E, La Vecchia C, Silverman D et al (2012) Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 23:374–382

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Bidel S, Hu G, Jousilahti P et al (2013) Coffee consumption and risk of gastric and pancreatic cancer – a prospective cohort study. Int J Cancer 132:1651–1659

    Article  PubMed  CAS  Google Scholar 

  19. Turati F, Galeone C, Edefonti V et al (2012) A meta-analysis of coffee consumption and pancreatic cancer. Ann Oncol 23:311–318

    Article  PubMed  CAS  Google Scholar 

  20. Dong J, Zou J, Yu XF (2011) Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies. World J Gastroenterol 17:1204–1210

    Article  PubMed Central  PubMed  Google Scholar 

  21. Han X, Li J, Brasky TM et al (2013) Antioxidant intake and pancreatic cancer risk: the Vitamins and Lifestyle (VITAL) Study. Cancer 119:1314–1320

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Rohrmann S, Linseisen J, Nothlings U et al (2013) Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 132:617–624

    Article  PubMed  CAS  Google Scholar 

  23. Arem H, Reedy J, Sampson J et al (2013) The Healthy Eating Index 2005 and risk for pancreatic cancer in the NIH-AARP study. J Natl Cancer Inst 105:1298–1305

    Article  PubMed Central  PubMed  Google Scholar 

  24. Li D, Morris JS, Liu J et al (2009) Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301:2553–2562

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Yuan C, Bao Y, Wu C et al (2013) Prediagnostic body mass index and pancreatic cancer survival. J Clin Oncol 31:4229–4234

    Article  PubMed Central  PubMed  Google Scholar 

  26. Aune D, Greenwood DC, Chan DS et al (2012) Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol 23:843–852

    Article  PubMed  CAS  Google Scholar 

  27. Chari ST, Leibson CL, Rabe KG et al (2008) Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 134:95–101

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Chari ST, Leibson CL, Rabe KG et al (2005) Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology 129:504–511

    Article  PubMed Central  PubMed  Google Scholar 

  29. Ben Q, Xu M, Ning X et al (2011) Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer 47:1928–1937

    Article  PubMed  Google Scholar 

  30. Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M (2005) Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 92:2076–2083

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Wang F, Herrington M, Larsson J, Permert J (2003) The relationship between diabetes and pancreatic cancer. Mol Cancer 2:4

    Article  PubMed Central  PubMed  Google Scholar 

  32. Stevens RJ, Roddam AW, Beral V (2007) Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer 96:507–509

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Soranna D, Scotti L, Zambon A et al (2012) Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist 17:813–822

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Bodmer M, Becker C, Meier C, Jick SS, Meier CR (2012) Use of antidiabetic agents and the risk of pancreatic cancer: a case-control analysis. Am J Gastroenterol 107:620–626

    Article  PubMed  CAS  Google Scholar 

  35. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL (2009) Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 137:482–488

    Article  PubMed Central  PubMed  Google Scholar 

  36. Lowenfels AB, Maisonneuve P, Cavallini G et al (1993) Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 328:1433–1437

    Article  PubMed  CAS  Google Scholar 

  37. Liou GY, Doppler H, Necela B et al (2013) Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-kappaB and MMPs. J Cell Biol 202:563–577

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Duell EJ, Lucenteforte E, Olson SH et al (2012) Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 23:2964–2970

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Hemminki K, Li X, Sundquist J, Sundquist K (2008) Cancer risks in ulcerative colitis patients. Int J Cancer 123:1417–1421

    Article  PubMed  CAS  Google Scholar 

  40. Hemminki K, Li X, Sundquist J, Sundquist K (2009) Cancer risks in Crohn disease patients. Ann Oncol 20:574–580

    Article  PubMed  CAS  Google Scholar 

  41. Bao Y, Spiegelman D, Li R et al (2010) History of peptic ulcer disease and pancreatic cancer risk in men. Gastroenterology 138:541–549

    Article  PubMed Central  PubMed  Google Scholar 

  42. Luo J, Nordenvall C, Nyren O et al (2007) The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer 120:368–372

    Article  PubMed  CAS  Google Scholar 

  43. Tascilar M, van Rees BP, Sturm PD et al (2002) Pancreatic cancer after remote peptic ulcer surgery. J Clin Pathol 55:340–345

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Xiao M, Wang Y, Gao Y (2013) Association between Helicobacter pylori infection and pancreatic cancer development: a meta-analysis. PLoS One 8:e75559

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Trikudanathan G, Philip A, Dasanu CA, Baker WL (2011) Association between Helicobacter pylori infection and pancreatic cancer. A cumulative meta-analysis. JOP 12:26–31

    PubMed  Google Scholar 

  46. Risch HA, Yu H, Lu L, Kidd MS (2010) ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: a case-control study. J Natl Cancer Inst 102:502–505

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. de Martel C, Llosa AE, Friedman GD et al (2008) Helicobacter pylori infection and development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 17:1188–1194

    Article  PubMed  Google Scholar 

  48. Hassan MM, Li D, El-Deeb AS et al (2008) Association between hepatitis B virus and pancreatic cancer. J Clin Oncol 26:4557–4562

    Article  PubMed Central  PubMed  Google Scholar 

  49. Xu JH, Fu JJ, Wang XL et al (2013) Hepatitis B or C viral infection and risk of pancreatic cancer: a meta-analysis of observational studies. World J Gastroenterol 19:4234–4241

    Article  PubMed Central  PubMed  Google Scholar 

  50. Michaud DS, Liu Y, Meyer M, Giovannucci E, Joshipura K (2008) Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol 9:550–558

    Article  PubMed Central  PubMed  Google Scholar 

  51. Arora M, Weuve J, Fall K, Pedersen NL, Mucci LA (2010) An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study. Am J Epidemiol 171:253–259

    Article  PubMed Central  PubMed  Google Scholar 

  52. Schernhammer ES, Kang JH, Chan AT et al (2004) A prospective study of aspirin use and the risk of pancreatic cancer in women. J Natl Cancer Inst 96:22–28

    Article  PubMed  CAS  Google Scholar 

  53. Jacobs EJ, Connell CJ, Rodriguez C et al (2004) Aspirin use and pancreatic cancer mortality in a large United States cohort. J Natl Cancer Inst 96:524–528

    Article  PubMed  CAS  Google Scholar 

  54. Anderson KE, Johnson TW, Lazovich D, Folsom AR (2002) Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J Natl Cancer Inst 94:1168–1171

    Article  PubMed  Google Scholar 

  55. Tan XL, Reid Lombardo KM, Bamlet WR et al (2011) Aspirin, nonsteroidal anti-inflammatory drugs, acetaminophen, and pancreatic cancer risk: a clinic-based case-control study. Cancer Prev Res (Phila) 4:1835–1841

    Article  CAS  Google Scholar 

  56. Holly EA, Eberle CA, Bracci PM (2003) Prior history of allergies and pancreatic cancer in the San Francisco Bay area. Am J Epidemiol 158:432–441

    Article  PubMed  Google Scholar 

  57. Gandini S, Lowenfels AB, Jaffee EM, Armstrong TD, Maisonneuve P (2005) Allergies and the risk of pancreatic cancer: a meta-analysis with review of epidemiology and biological mechanisms. Cancer Epidemiol Biomarkers Prev 14:1908–1916

    Article  PubMed  Google Scholar 

  58. Shen M, Boffetta P, Olsen JH et al (2006) A pooled analysis of second primary pancreatic cancer. Am J Epidemiol 163:502–511

    Article  PubMed  Google Scholar 

  59. Huang J, Valdimarsdottir U, Fall K, Ye W, Fang F (2013) Pancreatic cancer risk after loss of a child: a register-based study in Sweden during 1991–2009. Am J Epidemiol 178:582–589

    Article  PubMed  Google Scholar 

  60. Schuller HM, Al-Wadei HA, Ullah MF, Plummer HK 3rd (2012) Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. Carcinogenesis 33:191–196

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Jacobs EJ, Chanock SJ, Fuchs CS et al (2010) Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Int J Cancer 127:1421–1428

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  62. Brune KA, Lau B, Palmisano E et al (2010) Importance of age of onset in pancreatic cancer kindreds. J Natl Cancer Inst 102:119–126

    Article  PubMed Central  PubMed  Google Scholar 

  63. Wang L, Brune KA, Visvanathan K et al (2009) Elevated cancer mortality in the relatives of patients with pancreatic cancer. Cancer Epidemiol Biomarkers Prev 18:2829–2834

    Article  PubMed Central  PubMed  Google Scholar 

  64. Whitcomb DC (2012) Genetics of alcoholic and nonalcoholic pancreatitis. Curr Opin Gastroenterol 28:501–506

    Article  PubMed  Google Scholar 

  65. Couch FJ, Johnson MR, Rabe KG et al (2007) The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 16:342–346

    Article  PubMed  CAS  Google Scholar 

  66. Thompson D, Easton DF (2002) Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94:1358–1365

    Article  PubMed  CAS  Google Scholar 

  67. Lowery MA, Kelsen DP, Stadler ZK et al (2011) An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist 16:1397–1402

    Article  PubMed Central  PubMed  Google Scholar 

  68. Villarroel MC, Rajeshkumar NV, Garrido-Laguna I et al (2011) Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol Cancer Ther 10:3–8

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  69. Korsse SE, Harinck F, van Lier MG et al (2013) Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance. J Med Genet 50:59–64

    Article  PubMed  CAS  Google Scholar 

  70. Kastrinos F, Mukherjee B, Tayob N et al (2009) Risk of pancreatic cancer in families with Lynch syndrome. JAMA 302:1790–1795

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  71. Giardiello FM, Offerhaus GJ, Lee DH et al (1993) Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 34:1394–1396

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  72. Vasen HF, Gruis NA, Frants RR et al (2000) 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 87:809–811

    Article  PubMed  CAS  Google Scholar 

  73. Roberts NJ, Jiao Y, Yu J et al (2012) ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov 2:41–46

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Ruijs MW, Verhoef S, Rookus MA et al (2010) TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet 47:421–428

    Article  PubMed  CAS  Google Scholar 

  75. Wolpin BM, Chan AT, Hartge P et al (2009) ABO blood group and the risk of pancreatic cancer. J Natl Cancer Inst 101:424–431

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Amundadottir L, Kraft P, Stolzenberg-Solomon RZ et al (2009) Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 41:986–990

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  77. Hurban RH, Pitman MB, Klimstra DS (2007) Tumors in pancreas. In: AFIP atlas of tumor pathology. Fourth series, Fascicle 6. American Registry of Pathology/Armed Forces Institute of pathology, Washington DC

    Google Scholar 

  78. Jacobetz MA, Chan DS, Neesse A et al (2013) Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 62:112–120

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  79. Provenzano PP, Cuevas C, Chang AE et al (2012) Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21:418–429

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  80. Olive KP, Jacobetz MA, Davidson CJ et al (2009) Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324:1457–1461

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  81. Voong KR, Davison J, Pawlik TM et al (2010) Resected pancreatic adenosquamous carcinoma: clinicopathologic review and evaluation of adjuvant chemotherapy and radiation in 38 patients. Hum Pathol 41:113–122

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  82. Boyd CA, Benarroch-Gampel J, Sheffield KM, Cooksley CD, Riall TS (2012) 415 patients with adenosquamous carcinoma of the pancreas: a population-based analysis of prognosis and survival. J Surg Res 174:12–19

    Article  PubMed Central  PubMed  Google Scholar 

  83. Seidel G, Zahurak M, Iacobuzio-Donahue C et al (2002) Almost all infiltrating colloid carcinomas of the pancreas and periampullary region arise from in situ papillary neoplasms: a study of 39 cases. Am J Surg Pathol 26:56–63

    Article  PubMed  Google Scholar 

  84. Poultsides GA, Reddy S, Cameron JL et al (2010) Histopathologic basis for the favorable survival after resection of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas. Ann Surg 251:470–476

    Article  PubMed Central  PubMed  Google Scholar 

  85. Wilentz RE, Goggins M, Redston M et al (2000) Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: a newly described and characterized entity. Am J Pathol 156:1641–1651

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) (2010) WHO classification of tumours of the digestive system, 4th edn. IARC, Lyon

    Google Scholar 

  87. Laffan TA, Horton KM, Klein AP et al (2008) Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am J Roentgenol 191:802–807

    Article  PubMed Central  PubMed  Google Scholar 

  88. He J, Cameron JL, Ahuja N et al (2013) Is it necessary to follow patients after resection of a benign pancreatic intraductal papillary mucinous neoplasm? J Am Coll Surg 216:657–665, discussion 665–657

    Article  PubMed Central  PubMed  Google Scholar 

  89. Reddy S, Cameron JL, Scudiere J et al (2009) Surgical management of solid-pseudopapillary neoplasms of the pancreas (Franz or Hamoudi tumors): a large single-institutional series. J Am Coll Surg 208:950–957, discussion 957–959

    Article  PubMed Central  PubMed  Google Scholar 

  90. Wargo JA, Fernandez-del-Castillo C, Warshaw AL (2009) Management of pancreatic serous cystadenomas. Adv Surg 43:23–34

    Article  PubMed  Google Scholar 

  91. Jones S, Zhang X, Parsons DW et al (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321:1801–1806

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  92. Hruban RH, van Mansfeld AD, Offerhaus GJ et al (1993) K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol 143:545–554

    PubMed Central  PubMed  CAS  Google Scholar 

  93. Shi C, Fukushima N, Abe T et al (2008) Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. Cancer Biol Ther 7:353–360

    Article  PubMed  CAS  Google Scholar 

  94. Hahn SA, Schutte M, Hoque AT et al (1996) DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271:350–353

    Article  PubMed  CAS  Google Scholar 

  95. Iacobuzio-Donahue CA, Fu B, Yachida S et al (2009) DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 27:1806–1813

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  96. Blackford A, Serrano OK, Wolfgang CL et al (2009) SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res 15:4674–4679

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  97. NCIN Routes to Diagnosis report (Sept 2012)

    Google Scholar 

  98. Kalser MH, Barkin J, MacIntyre JM (1985) Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer 56:397–402

    Article  PubMed  CAS  Google Scholar 

  99. McGee S (2001) Palpation and percussion of the abdomen. In: Evidence based physical diagnosis. Saunders, Philadelphia, pp 601–604

    Google Scholar 

  100. Rickes S, Unkrodt K, Neye H, Ocran KW, Wermke W (2002) Differentiation of pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced power Doppler sonography. Scand J Gastroenterol 37:1313–1320

    Article  PubMed  CAS  Google Scholar 

  101. Karlson BM, Ekbom A, Lindgren PG, Kallskog V, Rastad J (1999) Abdominal US for diagnosis of pancreatic tumor: prospective cohort analysis. Radiology 213:107–111

    Article  PubMed  CAS  Google Scholar 

  102. Maringhini A, Ciambra M, Raimondo M et al (1993) Clinical presentation and ultrasonography in the diagnosis of pancreatic cancer. Pancreas 8:146–150

    Article  PubMed  CAS  Google Scholar 

  103. Ahn SS, Kim MJ, Choi JY et al (2009) Indicative findings of pancreatic cancer in prediagnostic CT. Eur Radiol 19:2448–2455

    Article  PubMed  Google Scholar 

  104. Vargas R, Nino-Murcia M, Trueblood W, Jeffrey RB Jr (2004) MDCT in pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR Am J Roentgenol 182:419–425

    Article  PubMed  Google Scholar 

  105. Li H, Zeng MS, Zhou KR, Jin DY, Lou WH (2006) Pancreatic adenocarcinoma: signs of vascular invasion determined by multi-detector row CT. Br J Radiol 79:880–887

    Article  PubMed  CAS  Google Scholar 

  106. Prokesch RW, Chow LC, Beaulieu CF, Bammer R, Jeffrey RB Jr (2002) Isoattenuating pancreatic adenocarcinoma at multi-detector row CT: secondary signs. Radiology 224:764–768

    Article  PubMed  Google Scholar 

  107. Zamboni GA, Kruskal JB, Vollmer CM et al (2007) Pancreatic adenocarcinoma: value of multidetector CT angiography in preoperative evaluation. Radiology 245:770–778

    Article  PubMed  Google Scholar 

  108. Miura F, Takada T, Amano H et al (2006) Diagnosis of pancreatic cancer. HPB (Oxford) 8:337–342

    Article  Google Scholar 

  109. Kondo H, Kanematsu M, Goshima S et al (2007) MDCT of the pancreas: optimizing scanning delay with a bolus-tracking technique for pancreatic, peripancreatic vascular, and hepatic contrast enhancement. AJR Am J Roentgenol 188:751–756

    Article  PubMed  Google Scholar 

  110. Raman SP, Horton KM, Fishman EK (2012) Multimodality imaging of pancreatic cancer-computed tomography, magnetic resonance imaging, and positron emission tomography. Cancer J 18:511–522

    Article  PubMed  Google Scholar 

  111. Takakura K, Sumiyama K, Munakata K et al (2011) Clinical usefulness of diffusion-weighted MR imaging for detection of pancreatic cancer: comparison with enhanced multidetector-row CT. Abdom Imaging 36:457–462

    Article  PubMed  Google Scholar 

  112. Ichikawa T, Sou H, Araki T et al (2001) Duct-penetrating sign at MRCP: usefulness for differentiating inflammatory pancreatic mass from pancreatic carcinomas. Radiology 221:107–116

    Article  PubMed  CAS  Google Scholar 

  113. Maccioni F, Martinelli M, Al Ansari N et al (2010) Magnetic resonance cholangiography: past, present and future: a review. Eur Rev Med Pharmacol Sci 14:721–725

    PubMed  CAS  Google Scholar 

  114. Adamek HE, Albert J, Breer H et al (2000) Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study. Lancet 356:190–193

    Article  PubMed  CAS  Google Scholar 

  115. Jailwala J, Fogel EL, Sherman S et al (2000) Triple-tissue sampling at ERCP in malignant biliary obstruction. Gastrointest Endosc 51:383–390

    Article  PubMed  CAS  Google Scholar 

  116. Li H, Hu Z, Chen J, Guo X (2014) Comparison of ERCP, EUS, and ERCP combined with EUS in diagnosing pancreatic neoplasms: a systematic review and meta-analysis. Tumour Biol 35:8867–8874

    Article  PubMed  CAS  Google Scholar 

  117. Kauhanen SP, Komar G, Seppanen MP et al (2009) A prospective diagnostic accuracy study of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg 250:957–963

    Article  PubMed  Google Scholar 

  118. Nishiyama Y, Yamamoto Y, Yokoe K et al (2005) Contribution of whole body FDG-PET to the detection of distant metastasis in pancreatic cancer. Ann Nucl Med 19:491–497

    Article  PubMed  Google Scholar 

  119. Singer E, Gschwantler M, Plattner D et al (2007) Differential diagnosis of benign and malign pancreatic masses with 18F-fluordeoxyglucose-positron emission tomography recorded with a dual-head coincidence gamma camera. Eur J Gastroenterol Hepatol 19:471–478

    Article  PubMed  Google Scholar 

  120. Yoshioka M, Sato T, Furuya T et al (2004) Role of positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose in evaluating the effects of arterial infusion chemotherapy and radiotherapy on pancreatic cancer. J Gastroenterol 39:50–55

    Article  PubMed  Google Scholar 

  121. Cameron K, Golan S, Simpson W et al (2011) Recurrent pancreatic carcinoma and cholangiocarcinoma: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Abdom Imaging 36:463–471

    Article  PubMed  Google Scholar 

  122. Ruf J, Lopez Hanninen E, Oettle H et al (2005) Detection of recurrent pancreatic cancer: comparison of FDG-PET with CT/MRI. Pancreatology 5:266–272

    Article  PubMed  Google Scholar 

  123. Heinrich S, Goerres GW, Schafer M et al (2005) Positron emission tomography/computed tomography influences on the management of resectable pancreatic cancer and its cost-effectiveness. Ann Surg 242:235–243

    Article  PubMed Central  PubMed  Google Scholar 

  124. Agarwal B, Ludwig OJ, Collins BT, Cortese C (2008) Immunostaining as an adjunct to cytology for diagnosis of pancreatic adenocarcinoma. Clin Gastroenterol Hepatol 6:1425–1431

    Article  PubMed  Google Scholar 

  125. Siddiqui AA, Brown LJ, Hong SK et al (2011) Relationship of pancreatic mass size and diagnostic yield of endoscopic ultrasound-guided fine needle aspiration. Dig Dis Sci 56:3370–3375

    Article  PubMed  Google Scholar 

  126. Chen J, Yang R, Lu Y, Xia Y, Zhou H (2012) Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a systematic review. J Cancer Res Clin Oncol 138:1433–1441

    Article  PubMed  Google Scholar 

  127. Harewood GC, Wiersema MJ (2002) Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses. Am J Gastroenterol 97:1386–1391

    Article  PubMed  Google Scholar 

  128. Puli SR, Bechtold ML, Buxbaum JL, Eloubeidi MA (2013) 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 42:20–26

    Article  PubMed  Google Scholar 

  129. Krishna NB, Mehra M, Reddy AV, Agarwal B (2009) EUS/EUS-FNA for suspected pancreatic cancer: influence of chronic pancreatitis and clinical presentation with or without obstructive jaundice on performance characteristics. Gastrointest Endosc 70:70–79

    Article  PubMed  Google Scholar 

  130. Chen VK, Eloubeidi MA (2004) Endoscopic ultrasound-guided fine needle aspiration is superior to lymph node echofeatures: a prospective evaluation of mediastinal and peri-intestinal lymphadenopathy. Am J Gastroenterol 99:628–633

    Article  PubMed  Google Scholar 

  131. Bipat S, Phoa SS, van Delden OM et al (2005) Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis. J Comput Assist Tomogr 29:438–445

    Article  PubMed  Google Scholar 

  132. Aslanian H, Salem R, Lee J et al (2005) EUS diagnosis of vascular invasion in pancreatic cancer: surgical and histologic correlates. Am J Gastroenterol 100:1381–1385

    Article  PubMed  Google Scholar 

  133. Fisher JM, Gordon SR, Gardner TB (2011) The impact of prior biliary stenting on the accuracy and complication rate of endoscopic ultrasound fine-needle aspiration for diagnosing pancreatic adenocarcinoma. Pancreas 40:21–24

    Article  PubMed  Google Scholar 

  134. Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE (2009) EUS elastography for the characterization of solid pancreatic masses. Gastrointest Endosc 70:1101–1108

    Article  PubMed  Google Scholar 

  135. Allen VB, Gurusamy KS, Takwoingi Y, Kalia A, Davidson BR (2013) Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev 11:CD009323

    PubMed  Google Scholar 

  136. Marrelli D, Caruso S, Pedrazzani C et al (2009) CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg 198:333–339

    Article  PubMed  CAS  Google Scholar 

  137. Satake K, Takeuchi T (1994) Comparison of CA19-9 with other tumor markers in the diagnosis of cancer of the pancreas. Pancreas 9:720–724

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  139. Goonetilleke KS, Siriwardena AK (2007) Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 33:266–270

    Article  PubMed  CAS  Google Scholar 

  140. Hartwig W, Strobel O, Hinz U et al (2013) CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol 20:2188–2196

    Article  PubMed  Google Scholar 

  141. Tian F, Appert HE, Myles J, Howard JM (1992) Prognostic value of serum CA 19-9 levels in pancreatic adenocarcinoma. Ann Surg 215:350–355

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  142. Micke O, Bruns F, Schafer U et al (2003) CA 19-9 in the therapy monitoring and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy. Anticancer Res 23:835–840

    PubMed  CAS  Google Scholar 

  143. Fritz S, Hackert T, Hinz U et al (2011) Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas. Br J Surg 98:104–110

    Article  PubMed  CAS  Google Scholar 

  144. Mann DV, Edwards R, Ho S, Lau WY, Glazer G (2000) Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol 26:474–479

    Article  PubMed  CAS  Google Scholar 

  145. Locker GY, Hamilton S, Harris J et al (2006) ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 24:5313–5327

    Article  PubMed  CAS  Google Scholar 

  146. Ruckert F, Pilarsky C, Grutzmann R (2010) Serum tumor markers in pancreatic cancer-recent discoveries. Cancers (Basel) 2:1107–1124

    Article  CAS  Google Scholar 

  147. Grote T, Logsdon CD (2007) Progress on molecular markers of pancreatic cancer. Curr Opin Gastroenterol 23:508–514

    Article  PubMed  CAS  Google Scholar 

  148. Bunger S, Laubert T, Roblick UJ, Habermann JK (2011) Serum biomarkers for improved diagnostic of pancreatic cancer: a current overview. J Cancer Res Clin Oncol 137:375–389

    Article  PubMed  CAS  Google Scholar 

  149. Kulu Y, Schmied BM, Werner J et al (2009) Total pancreatectomy for pancreatic cancer: indications and operative technique. HPB (Oxford) 11:469–475

    Article  Google Scholar 

  150. Hartwig W, Vollmer CM, Fingerhut A et al (2014) Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS). Surgery 156:1–14

    Article  PubMed  Google Scholar 

  151. Adham M, Bredt LC, Robert M et al (2014) Pancreatic resection in elderly patients: should it be denied? Langenbecks Arch Surg 399:449–459

    Article  PubMed  CAS  Google Scholar 

  152. Venkat R, Edil BH, Schulick RD et al (2012) Laparoscopic distal pancreatectomy is associated with significantly less overall morbidity compared to the open technique: a systematic review and meta-analysis. Ann Surg 255:1048–1059

    Article  PubMed  Google Scholar 

  153. Winter JM, Cameron JL, Campbell KA et al (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg 10:1199–1210, discussion 1210–1191

    Article  PubMed  Google Scholar 

  154. Kim HJ, Czischke K, Brennan MF, Conlon KC (2002) Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg 6:763–769

    Article  PubMed  Google Scholar 

  155. Palmer DH, Stocken DD, Hewitt H et al (2007) A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol 14:2088–2096

    Article  PubMed  Google Scholar 

  156. Evans DB, Varadhachary GR, Crane CH et al (2008) Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26:3496–3502

    Article  PubMed  CAS  Google Scholar 

  157. Varadhachary GR, Wolff RA, Crane CH et al (2008) Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26:3487–3495

    Article  PubMed  CAS  Google Scholar 

  158. Pisters PW, Wolff RA, Janjan NA et al (2002) Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol 20:2537–2544

    Article  PubMed  CAS  Google Scholar 

  159. Massucco P, Capussotti L, Magnino A et al (2006) Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival. Ann Surg Oncol 13:1201–1208

    Article  PubMed  Google Scholar 

  160. Patel M, Hoffe S, Malafa M et al (2011) Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. J Surg Oncol 104:155–161

    Article  PubMed Central  PubMed  Google Scholar 

  161. Stokes JB, Nolan NJ, Stelow EB et al (2011) Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 18:619–627

    Article  PubMed  Google Scholar 

  162. Kim EJ, Ben-Josef E, Herman JM et al (2013) A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer 119:2692–2700

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  163. Katz MH, Pisters PW, Evans DB et al (2008) Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 206:833–846, discussion 846–838

    Article  PubMed  Google Scholar 

  164. Louvet C, Labianca R, Hammel P et al (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23:3509–3516

    Article  PubMed  CAS  Google Scholar 

  165. Sahora K, Kuehrer I, Eisenhut A et al (2011) NeoGemOx: gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery 149:311–320

    Article  PubMed  Google Scholar 

  166. Reni M, Cereda S, Balzano G et al (2009) Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol 64:1253–1259

    Article  PubMed  CAS  Google Scholar 

  167. Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7:e1000267

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  168. (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59:2006–2010

    Google Scholar 

  169. Klinkenbijl JH, Jeekel J, Sahmoud T et al (1999) Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230:776–782, discussion 782–774

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  170. Neoptolemos JP, Stocken DD, Friess H et al (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210

    Article  PubMed  CAS  Google Scholar 

  171. Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277

    Article  PubMed  CAS  Google Scholar 

  172. Ueno H, Kosuge T, Matsuyama Y et al (2009) A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer 101:908–915

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  173. Neoptolemos JP, Stocken DD, Bassi C et al (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081

    Article  PubMed  CAS  Google Scholar 

  174. Regine WF, Winter KA, Abrams RA et al (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299:1019–1026

    Article  PubMed  CAS  Google Scholar 

  175. Fukutomi A et al (2013) JASPAC 01: randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer. ASCO Meet Abstr 31:4008

    Google Scholar 

  176. Hsu CC, Herman JM, Corsini MM et al (2010) Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol 17:981–990

    Article  PubMed Central  PubMed  Google Scholar 

  177. Liao WC, Chien KL, Lin YL et al (2013) Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis. Lancet Oncol 14:1095–1103

    Article  PubMed  Google Scholar 

  178. Schmidt J, Abel U, Debus J et al (2012) Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. J Clin Oncol 30:4077–4083

    Article  PubMed  CAS  Google Scholar 

  179. Heestand GM et al (2014) A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704. ASCO Meet Abstr 32:176

    Google Scholar 

  180. Hardacre JM, Mulcahy M, Small W et al (2013) Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J Gastrointest Surg 17:94–100, discussion p 100–101

    Article  PubMed  Google Scholar 

  181. Fisher SB, Patel SH, Bagci P et al (2013) An analysis of human equilibrative nucleoside transporter-1, ribonucleoside reductase subunit M1, ribonucleoside reductase subunit M2, and excision repair cross-complementing gene-1 expression in patients with resected pancreas adenocarcinoma: implications for adjuvant treatment. Cancer 119:445–453

    Article  PubMed  CAS  Google Scholar 

  182. Bachet JB, Marechal R, Demetter P et al (2012) Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma. Ann Oncol 23:2327–2335

    Article  PubMed  CAS  Google Scholar 

  183. Hidalgo M (2010) Pancreatic cancer. N Engl J Med 362:1605–1617

    Article  PubMed  CAS  Google Scholar 

  184. Burris HA 3rd, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413

    PubMed  CAS  Google Scholar 

  185. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C (2008) Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 8:82

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  186. Sultana A, Smith CT, Cunningham D et al (2007) Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 25:2607–2615

    Article  PubMed  Google Scholar 

  187. Ciliberto D, Botta C, Correale P et al (2013) Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomised trials. Eur J Cancer 49:593–603

    Article  PubMed  CAS  Google Scholar 

  188. De Jesus-Acosta A, Oliver GR, Blackford A et al (2012) A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol 69:415–424

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  189. Reni M, Cordio S, Milandri C et al (2005) Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol 6:369–376

    Article  PubMed  CAS  Google Scholar 

  190. Moore MJ, Goldstein D, Hamm J et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1960–1966

    Article  PubMed  CAS  Google Scholar 

  191. Philip PA, Benedetti J, Corless CL et al (2010) Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 28:3605–3610

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  192. Van Cutsem E, Vervenne WL, Bennouna J et al (2009) Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 27:2231–2237

    Article  PubMed  CAS  Google Scholar 

  193. Spano JP, Chodkiewicz C, Maurel J et al (2008) Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet 371:2101–2108

    Article  PubMed  CAS  Google Scholar 

  194. Goncalves A, Gilabert M, Francois E et al (2012) BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. Ann Oncol 23:2799–2805

    Article  PubMed  CAS  Google Scholar 

  195. Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703

    Article  CAS  Google Scholar 

  196. Edmonds C, Cengel KA (2008) Tumor-Stroma interactions in pancreatic cancer: will this SPARC prove a raging fire? Cancer Biol Ther 7:1816–1817

    Article  PubMed  CAS  Google Scholar 

  197. Infante JR, Matsubayashi H, Sato N et al (2007) Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol 25:319–325

    Article  PubMed  Google Scholar 

  198. Ducreux M, Mitry E, Ould-Kaci M et al (2004) Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol 15:467–473

    Article  PubMed  CAS  Google Scholar 

  199. Boeck S, Hoehler T, Seipelt G et al (2008) Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer. Ann Oncol 19:340–347

    Article  PubMed  CAS  Google Scholar 

  200. Ducreux M, Rougier P, Pignon JP et al (2002) A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic carcinoma. Ann Oncol 13:1185–1191

    Article  PubMed  CAS  Google Scholar 

  201. Maisey N, Chau I, Cunningham D et al (2002) Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer. J Clin Oncol 20:3130–3136

    Article  PubMed  CAS  Google Scholar 

  202. Taieb J, Lecomte T, Aparicio T et al (2007) FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study. Ann Oncol 18:498–503

    Article  PubMed  CAS  Google Scholar 

  203. Stathopoulos GP, Syrigos K, Aravantinos G et al (2006) A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. Br J Cancer 95:587–592

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  204. Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825

    Article  PubMed  CAS  Google Scholar 

  205. Ramanathan RK, Lee KM, McKolanis J et al (2005) Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol Immunother 54:254–264

    Article  PubMed  CAS  Google Scholar 

  206. Rong Y, Qin X, Jin D et al (2012) A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer. Clin Exp Med 12:173–180

    Article  PubMed  CAS  Google Scholar 

  207. Kaufman HL, Kim-Schulze S, Manson K et al (2007) Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. J Transl Med 5:60

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  208. Therion Reports Results of Phase 3 PANVAC-VF trial and announces plans for company sale. PR Newswire, 28 June. Available online: http://www.prnewswire.com

  209. Le DT, Lutz E, Uram JN et al (2013) Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 36:382–389

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  210. Le DT, Wang-Gillam A, Picozzi V et al (2014) A phase 2, randomized trial of GVAX pancreas and CRS-207 immunotherapy versus GVAX alone in patients with metastatic pancreatic adenocarcinoma: updated results. J Clin Oncol 32:abstr 177

    Google Scholar 

  211. Zabernigg A, Giesinger JM, Pall G et al (2012) Quality of life across chemotherapy lines in patients with cancers of the pancreas and biliary tract. BMC Cancer 12:390

    Article  PubMed Central  PubMed  Google Scholar 

  212. Kuwahara A et al (2012) Symptom changes that predict disease control by systemic chemotherapy in patients with advanced pancreatic cancer. ASCO Meet Abstr 4:195

    Google Scholar 

  213. Wong GY, Schroeder DR, Carns PE et al (2004) Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. JAMA 291:1092–1099

    Article  PubMed  CAS  Google Scholar 

  214. Smith TJ, Staats PS, Deer T et al (2002) Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol 20:4040–4049

    Article  PubMed  CAS  Google Scholar 

  215. Mayr M, Schmid RM (2010) Pancreatic cancer and depression: myth and truth. BMC Cancer 10:569

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, The Royal Marsden Hospital NHS Foundation Trust, London, UK

    Georgios Antoniou M.D.

  2. Department of Gastroenterology, Laiko University Hospital, Athens, Greece

    Ioannis Koutsounas M.D.

  3. Department of Medical Oncology, BOC Oncology Centre, Nicosia, Cyprus

    Panteleimon Kountourakis M.D., Ph.D.

  4. Department of General Medicine, The Royal Free Hospital NHS Foundation Trust, London, UK

    Christos Pontas M.D.

  5. Department Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal

    Ramon Andrade de Mello M.D., Ph.D.

  6. Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal

    Ramon Andrade de Mello M.D., Ph.D.

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  1. Georgios Antoniou M.D.
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  3. Panteleimon Kountourakis M.D., Ph.D.
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Correspondence to Ramon Andrade de Mello M.D., Ph.D. .

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  1. Medical Oncology, University of Algarve, Faro, Portugal

    Ramon Andrade de Mello

  2. edificio 7, ala nascente, 3º andar, University of Algarve, Dept Cie Biomed edificio 7, ala nascente, 3º andar, Faro, Portugal

    Álvaro Tavares

  3. Medical Oncology, University of Athens, Athens, Greece

    Giannis Mountzios

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Antoniou, G., Koutsounas, I., Kountourakis, P., Pontas, C., de Mello, R.A. (2015). Pancreatic Cancer. In: de Mello, R., Tavares, Á., Mountzios, G. (eds) International Manual of Oncology Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-21683-6_17

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