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Pancreatic Adenocarcinoma Surveillance Counterpoint: Europe

  • Richard A. Smith
  • Jane V. Butler
  • John P. NeoptolemosEmail author
Chapter
Part of the Current Clinical Oncology book series (CCO)

Abstract

Exocrine pancreatic cancer accounts for almost a quarter of a million deaths worldwide each year with approximately one third arising in Europe [1, 2]. Despite being only the thirteenth most common malignancy worldwide, it is the eighth most frequent cause of cancer mortality [2]. The singularly aggressive nature of this disease is further underlined by the fact that mortality rates continue to approximate the incidence [3]. There has been a marginal decline in both age-standardised incidence and mortality rates over the past 20 years [3, 4].

Keywords

United Kingdom Exocrine Signet ring cell carcinoma Penetrance Pancreatoduodenectomy 

Notes

Glossary

Ductal adenocarcinoma

Carcinoma arising from epithelial cells within the pancreatic duct

Mucinous non-cyctic neoplasm

Cysts lined by mucin-producing cells may be unilocular or multilocular

Signet ring cell carcinoma

Cancer derived from epithelial cells with a characteristic histological appearance resembling a signet ring

Autosomal dominant

Mode of inheritance whereby inheritance of one copy of an abnormal gene from a non-XY chromosome will result in expression of the phenotype

Penetrance (genetics)

The proportion of those carrying the gene mutation who express the phenotype, e.g. penetrance is said to be incomplete if a certain proportion of those with the mutation do not exhibit any clinical features of the trait; penetrance is complete of all those individuals carrying the mutation express the trait

Pancreatoduodenectomy

Surgical removal of the head of the pancreas and most of the duodenum, usually pylorus preserving

Kausch Whipple

Eponymous name associated with pancreatoduodenectomy; Walther Kausch performed the first surgical removal of the duodenum and a portion of the pancreas in a two-stage procedure in 1912: Allen Whipple performed the procedure at a later date before adopting a one-stage technique

Anastomosis

A surgical join between two hollow structures; this join may leak (anastomotic leak) and may cause narrowing (anastomotic stricture) in the event of a fibrous scar tissue formation

References

  1. 1.
  2. 2.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Fitzsimmons D, Osmond C, George S, Johnson CD. Trends in stomach and pancreatic cancer incidence and mortality in England and Wales, 1951–2000. Br J Surg. 2007;94:1162–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Horner MJ, Ries LAG, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda MD, http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site, 2009
  6. 6.
    Ansary-Moghaddam A, Huxley R, Barzi F, et al. The effect of modifiable risk factors on pancreatic cancer mortality in populations of the Asia-Pacific region. Cancer Epidemiol Biomarkers Prev. 2006;15:2435–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Qui D, Kurosawa M, Lin Y, et al. Overview of the epidemiology of pancreatic cancer focusing on the JACC study. J Epidemiology. 2005;15(Suppl II):S157–S167Google Scholar
  8. 8.
    Larsson SC, Permert J, Hakansson N, Näslund I, Bergkvist L, Wolk A. Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts. Br J Cancer. 2005;93:1310–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Luo J, Iwasaki M, Inuoe M, et al. Body mass index, physical activity and the risk of pancreatic cancer in relation to smoking status and history of diabetes: a large scale population-based cohort study in Japan—the JPHC study. Cancer Causes Control. 2007;18:603–12.PubMedCrossRefGoogle Scholar
  10. 10.
    Hassan MM, Bondy ML, Wolff R, et al. Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol. 2007;102:2696–707.PubMedCrossRefGoogle Scholar
  11. 11.
    Iodice S, Gandini S, Maisonneuve P, Lowenfels A. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch Surg. 2008;393:535–45.PubMedCrossRefGoogle Scholar
  12. 12.
    Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary meat, dairy products, fat and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol. 2003;157:1115–25.PubMedCrossRefGoogle Scholar
  13. 13.
    Stolzenberg-Solomon RZ, Cross AJ, Silverman DT, et al. Meat and meat mutagen intake and pancreatic cancer risk in the NIH-AARP cohort. Cancer Epidemiol Biomarkers Prev. 2007;16:2664–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Silverman DT, Schiffman M, Everhart J, et al. Diabetes mellitus, other medical conditions and family history of cancer as risk factors for pancreatic cancer. Br J Cancer. 1999;80:1830–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Pannala R, Basu A, Petersen GM, Chari ST. New onset diabetes: a potential clue to then early diagnosis of pancreatic cancer. Lancet Oncol. 2009;10:88–95.PubMedCrossRefGoogle Scholar
  16. 16.
    Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328:1433–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Lowenfels AB, Maisonneuve P, DiMagno E, et al. Hereditary Pancreatitis and the risk of pancreatic cancer. J Natl Cancer Inst. 1997;89:442–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Howes N, Lerch M, Greenhalf W, et al. Clinical and genetic characteristics of hereditary pancreatitis. Clin Gastroenterol Hepatol. 2004;2:252–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64:2634–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Alexakis N, Halloran C, Raraty M, Gbaneh P, Neoptolemos JP. Current standards of surgery for pancreatic cancer. Br J Surg. 2004;91:1410–27.PubMedCrossRefGoogle Scholar
  21. 21.
    Shapiro TM. Adenocarcinoma of the pancreas: a statistical analysis of biliary bypass vs. Whipple resection in good risk patients. Ann Surg. 1975;182:715–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Gudjonsson B. Cancer of the pancreas: 50 years of surgery. Cancer. 1987;60:2284–303.PubMedCrossRefGoogle Scholar
  23. 23.
    Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas - 616 patients: results, outcomes and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.PubMedCrossRefGoogle Scholar
  24. 24.
    Raut CP, Tseng JF, Sun CC, et al. Impact of resection margin status on pattern of failure after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52–60.PubMedCrossRefGoogle Scholar
  25. 25.
    van Heek NT, Kuhlmann KF, Schloten RJ, et al. Hospital volume and mortality after pancreatic resection: a systematic review and an evaluation of intervention in the Netherlands. Ann Surg. 2005;242:781–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Büchler MW, Wagner M, Schmied BM, Uhl W, Friess H, Z’graggen K. Changes in morbidity after pancreatic resection. Arch Surg. 2003;138:1310–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Birkmeyer JD, Warshaw AL, Finlayson SR, Grove MR, Tosteson AN. Relationship between hospital volume and late survival after pancreaticoduodenectomy. Surgery. 1999;126:178–83.PubMedCrossRefGoogle Scholar
  28. 28.
    Neoptolemos JP, Stocken DD, Friess H, et al. European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.PubMedCrossRefGoogle Scholar
  29. 29.
    Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.PubMedCrossRefGoogle Scholar
  30. 30.
    Seiler CA, Wagner M, Bachmann T, et al. Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection-long term results. Br J Surg. 2005;92:547–56.PubMedCrossRefGoogle Scholar
  31. 31.
    Tran KT, Smeenk HG, van Eijck CH, et al. Pylorus preserving ­pancreaticoduo-denectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors. Ann Surg. 2004;240:738–45.PubMedCrossRefGoogle Scholar
  32. 32.
    Pedrazzoli S, DiCarlo V, Dionigi R, et al. Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg. 1998;228:508–17.PubMedCrossRefGoogle Scholar
  33. 33.
    Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg. 2002;236:355–66.PubMedCrossRefGoogle Scholar
  34. 34.
    Henne-Bruns D, Vogel I, Luttges J, Klöppel G, Kremer B. Surgery for ductal adenocarcinoma of the pancreatic head: staging, complications and survival after regional versus extended lymphadenectomy. World J Surg. 2000;24:595–601.PubMedCrossRefGoogle Scholar
  35. 35.
    Bold RJ, Charnsangavej C, Cleary KR, et al. Major vascular resection as part of pancreaticoduodenectomy for cancer: radiologic, intraoperative, and pathologic analysis. J Gastrointest Surg. 1999;3:233–43.PubMedCrossRefGoogle Scholar
  36. 36.
    van Geenan RC, ten Kate FJ, de Wit LT, van Gulik TM, Obertop H, Douma DJ. Segmental resection and wedge excision of the portal or superior mesenteric vein during pancreatoduodenectomy. Surgery. 2001;129:158–63.CrossRefGoogle Scholar
  37. 37.
    Nakagohri T, Kinoshita T, Konishi M, Inoue K, Takahashi S. Survival benefits of portal vein resection for pancreatic cancer. Am J Surg. 2003;186:149–53.PubMedCrossRefGoogle Scholar
  38. 38.
    Halloran CM, Ghaneh P, Bosonnet L, et al. Complications of pancreatic cancer resection. Dig Surg. 2002;19:138–46.PubMedCrossRefGoogle Scholar
  39. 39.
    Büchler MW, Wagner M, Schmied BM, et al. Changes in morbidity after pancreatic resection. Arch Surg. 2003;138:1310–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Müller MW, Friess H, Kleeff J, et al. Is there still a role for total pancreatectomy? Ann Surg. 2007;246:966–74.PubMedCrossRefGoogle Scholar
  41. 41.
    Huang JJ, Yeo CJ, Sohn TA, et al. Quality of life and outcomes after pancreaticoduodenectomy. Ann Surg. 2000;231:890–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Rault A, SaCunha A, Klopfenstein D, et al. Pancreaticojejunal anastomosis is preferable to pancreaticogastrostomy after pancreaticoduodenectomy for long-term outcomes of pancreatic exocrine function. J Am Coll Surg. 2005;201:239–44.PubMedCrossRefGoogle Scholar
  43. 43.
    Tran TCK, van‘t Hof G, Kazemier G, et al. Pancreatic fibrosis correlates with exocrine insufficiency after pancreatoduodenectomy. Dig Surg. 2008;25:311–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Halloran CM, Taylor S, Chauhan S, et al. Pancreatic exocrine failure is common following partial pancreatic resection for tumour. (In press)Google Scholar
  45. 45.
    Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 1995;273:1605–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young onset diabetes: systematic review and meta-analysis. Br J Cancer. 2007;96:507–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Huxley R, Ansary-Moghaddam A, de Berrington GA, Barzi F, Woodward M. Type II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005;92:2076–833.PubMedCrossRefGoogle Scholar
  48. 48.
    Gullo L, Pezzilli R, Morselli-Labate AM, Italian Pancreatic Cancer Study Group. Diabetes and the risk of pancreatic cancer. N Engl J Med. 1994;331:81–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Permert J, Ihse I, Jorfeldt L, von Schenk H, Arnqvist HJ, Larsson J. Pancreatic cancer is associated with impaired glucose metabolism. Eur J Surg. 1993;159:101–7.PubMedGoogle Scholar
  50. 50.
    Litwin J, Dobrowolski S, Orłowska-Kunikowska E, Sledziński Z. Changes in glucose metabolism after Kausch-Whipple pancreatectomy in pancreatic cancer and chronic pancreatitis patients. Pancreas. 2008;36:26–30.PubMedCrossRefGoogle Scholar
  51. 51.
    Pannala R, Leirness JB, Bamlet WR, Ananda B, Peterson GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134:981–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Basso D, Greco E, Fogar P, et al. Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause? Clin Chim Acta. 2006;372:120–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Lillemoe KD, Pitt HA. Periampullary adenocarcinoma: analysis of 5-year survivors. Ann Surg. 1998;227:821–31.PubMedCrossRefGoogle Scholar
  54. 54.
    Braasch JW, Deziel DJ, Rossi RL, Watkins Jr E, Winter PF. Pyloric and gastric preserving pancreatic resection. Experience with 87 patients. Ann Surg. 1986;204:411–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Grace PA, Pitt HA, Longmire WP. Pylorus preserving pancreatoduodenectomy: an overview. Br J Surg. 1990;77:968–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Sakaguchi T, Nakamura S, Suzuki S, et al. Marginal ulceration after pylorus-preserving pancreaticoduodenectomy. J Hepatobiliary Pancreat Surg. 2000;7:193–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Ghaneh P, Neoptolemos JP. Pancreatic exocrine insufficiency following pancreatic resection. Digestion. 1999;60:104–10.PubMedCrossRefGoogle Scholar
  58. 58.
    Kahl S, Malfertheiner P. Exocrine and endocrine pancreatic insufficiency after pancreatic surgery. Best Pract Res Clin Gastroenterol. 2004;18:947–55.PubMedGoogle Scholar
  59. 59.
    Reid-Lombardo KM, la Ramos-De MA, Thomsen K, Harmsen WS, Farnell MB. Long-term anastomotic complications after pancreaticoduodenectomy for benign diseases. J Gastrointest Surg. 2007;11:1704–11.PubMedCrossRefGoogle Scholar
  60. 60.
    Fang WL, Su CH, Shyr YM, et al. Functional and morphological changes in pancreatic remnant after pancreaticoduodenectomy. Pancreas. 2007;35:361–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Laviano A, Meguid MM, Rossi-Fanelli F. Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol. 2003;4:686–94.PubMedCrossRefGoogle Scholar
  62. 62.
    Smith RA, Dajani K, Dodd S, et al. Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2008;15:3138–46.PubMedCrossRefGoogle Scholar
  63. 63.
    Giger U, Büchler M, Farhadi J, et al. Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study. Ann Surg Oncol. 2007;14:2798–806.PubMedCrossRefGoogle Scholar
  64. 64.
    Armstrong T, Walters E, Varshney S, Johnson CD. Deficiencies of micronutrients, altered bowel function, and quality of life during late follow-up after pancreaticoduodenectomy for malignancy. Pancreatology. 2002;2:528–34.PubMedCrossRefGoogle Scholar
  65. 65.
    Armstrong T, Strommer L, Ruiz-Jasbon F, et al. Pancreaticoduodenectomy for peri-ampullary neoplasia leads to specific micronutrient deficiencies. Pancreatology. 2007;7:37–44.PubMedCrossRefGoogle Scholar
  66. 66.
    Niedergethmann M, Shang E, Farag SM, et al. Early and enduring nutritional and functional results of pylorus preservation vs. classic Whipple procedure for pancreatic cancer. Langenbecks Arch Surg. 2006;391:195–202.PubMedCrossRefGoogle Scholar
  67. 67.
    Moertel CG, Childs DS, Reitmeier RJ, Colby Jr MY, Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969;2:865–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Kalser MH, Ellenberg SS. Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120:899–903.PubMedCrossRefGoogle Scholar
  69. 69.
    Gastrointestinal Tumour Study Group. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer. 1987;59:2006–10.CrossRefGoogle Scholar
  70. 70.
    UK Pancreatic Cancer Group. Adjuvant radiotherapy and follow-on chemotherapy in patients with pancreatic cancer: results of the UK Pancreatic Cancer Group Study (UKPACA-1). GI Cancer. 1998;2:235–45.Google Scholar
  71. 71.
    Klinkenbijl JH, Jeekel J, Sahmoud T, et al. 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. 1999;230:776–84.PubMedCrossRefGoogle Scholar
  72. 72.
    Smeenk HG, van Eijck CH, Hop WC, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007;246:734–40.PubMedCrossRefGoogle Scholar
  73. 73.
    Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358:1576–85.PubMedCrossRefGoogle Scholar
  74. 74.
    Stocken DD, Büchler MW, Dervenis C, et al. Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer. 2005;92:1372–82.PubMedCrossRefGoogle Scholar
  75. 75.
    Bakkevold KE, Arnesjo B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater - results of a controlled, prospective, randomised multicentre study. Eur J Cancer. 1993;29:698–703.CrossRefGoogle Scholar
  76. 76.
    Takada A, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A Phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer. 2002;95:1685–95.PubMedCrossRefGoogle Scholar
  77. 77.
    ESPAC-3(v2) phase III adjuvant trial in pancreatic cancer comparing 5-FU and D-L-folinic acid vs gemcitabine. National cancer research network trial portfolio (http://www.ncrn.org.uk/)
  78. 78.
    Regine WF, Winter KA, Abrams RA, et al. Flurouracil vs Gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299:1019–26.PubMedCrossRefGoogle Scholar
  79. 79.
    Splinter TA, Obertop H, Kok TC, et al. Adjuvant chemotherapy after resection of adenocarcinoma of the periampullary region and the head of the pancreas. A non-randomized pilot study. J Cancer Res Clin Oncol. 1989;115:200–2.PubMedCrossRefGoogle Scholar
  80. 80.
    Kurosaki I, Hatakeyama K. Adjuvant systemic chemotherapy with gemcitabine for stage IV pancreatic cancer: a preliminary report of initial experience. Chemotherapy. 2005;51:305–10.PubMedCrossRefGoogle Scholar
  81. 81.
    Kosuge T, Kiuchi T, Mukai K, et al. A multicentre randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol. 2006;36:159–65.PubMedCrossRefGoogle Scholar
  82. 82.
    Pawlik TM, Gleisner AL, Cameron JL, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141:610–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Bassi C, Stocken DD, Olah A, et al. European Study Group for Pancreatic Cancer (ESPAC). Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial. Dig Surg. 2005;22:353–63.PubMedCrossRefGoogle Scholar
  84. 84.
    Butturini G, Stocken DD, Wente MN, et al. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg. 2008;143:75–83.PubMedCrossRefGoogle Scholar
  85. 85.
    Smith RA, Bosonnet L, Ghaneh P, et al. Preoperative CA19-9 levels and lymph node ratio are independent predictors of survival in patients with resected pancreatic ductal adenocarcinoma. Dig Surg. 2008;25:226–32.PubMedCrossRefGoogle Scholar
  86. 86.
    Berger AC, Sigurdson ER, Le Voyer TE, et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol. 2005;23:8706–12.PubMedCrossRefGoogle Scholar
  87. 87.
    Inoue K, Nakane Y, Iiyama H, et al. The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol. 2002;9:27–34.PubMedCrossRefGoogle Scholar
  88. 88.
    Verbeke CS, Leitch D, Menon KV, et al. Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006;93:1232–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.PubMedCrossRefGoogle Scholar
  90. 90.
    Campbell F, Bennett M, Foulis AJ. Minimum dataset for histopathology reporting of pancreatic, ampulla of Vater and bile duct carcinoma. Royal college of pathologists. 2002; http://www.rcpath.org
  91. 91.
    Campbell F, Smith RA, Whelan P et al. Classification of R1 resections for pancreatic cancer: The prognostic relevance of tumour involvement within 1 mm of a resection margin. (In press)Google Scholar
  92. 92.
    De Braud F, Cascinu S, Gatta G. Cancer of pancreas. Critical Reviews In Oncology/Haematology. 2004;50:147–55.CrossRefGoogle Scholar
  93. 93.
    Linder S, Parrado C, Falkmer UG, et al. Prognostic significance of Ki-67 antigen and p53 protein expression in pancreatic duct carcinoma: a study of the monoclonal antibodies MIB-1 and DO-7 in formalin-fixed paraffin-embedded tumour material. Br J Cancer. 1997;76:54–9.PubMedCrossRefGoogle Scholar
  94. 94.
    DiGiuseppe JA, Hruban RH, Goodman SN, et al. Overexpression of p53 protein in adenocarcinoma of the pancreas. Am J Clin Pathol. 1994;101:684–8.PubMedGoogle Scholar
  95. 95.
    Song MM, Nio Y, Sato Y, et al. Clinicopathological significance of Ki-ras point mutation and p21 expression in beign and malignant tumors of the human pancreas. Int J Pancreatol. 1996;20:85–93.PubMedGoogle Scholar
  96. 96.
    Coppola D, Lu L, Fruehauf JP, et al. Analysis of p53, p21WAF1, and TGF-beta1 in human ductal adenocarcinoma of the pancreas: TGF-beta1 protein expression predicts longer survival. Am J Clin Pathol. 1998;110:16–23.PubMedGoogle Scholar
  97. 97.
    Tascilar M, Skinner HG, Rosty C, et al. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2001;7:4115–21.PubMedGoogle Scholar
  98. 98.
    Biankin AV, Morey AL, Lee CS, et al. DPC4/Smad4 expression and outcome in pancreatic ductal adenocarcinoma. J Clin Oncol. 2002;20:4531–42.PubMedCrossRefGoogle Scholar
  99. 99.
    Hua Z, Zhang YC, Hu XM, et al. Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma. World J Gastroenterol. 2003;9:2764–7.PubMedGoogle Scholar
  100. 100.
    Toga T, Nio Y, Hashimoto K, et al. The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome. Anticancer Res. 2004;24:1173–8.PubMedGoogle Scholar
  101. 101.
    Khorana AA, Hu YC, Ryan CK, et al. Vascular endothelial growth factor and DPC4 predict adjuvant therapy outcomes in resected pancreatic cancer. J Gastrointest Surg. 2005;9:903–11.PubMedCrossRefGoogle Scholar
  102. 102.
    Hamacher R, Schmid RM, Saur D, et al. Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer. 2008;7:64.PubMedCrossRefGoogle Scholar
  103. 103.
    Dong M, Zhou JP, Zhang H, et al. Clinicopathological significance of Bcl-2 and Bax protein expression in human pancreatic cancer. World J Gastroenterol. 2005;11:2744–7.PubMedGoogle Scholar
  104. 104.
    Bold RJ, Hess KR, Pearson AS, et al. Prognostic factors in resectable pancreatic cancer: p53 and bcl-2. J Gastrointest Surg. 1999;3:263–77.PubMedCrossRefGoogle Scholar
  105. 105.
    Friess H, Lu Z, Graber HU, et al. Bax, but not bcl-2, influences the prognosis of human pancreatic cancer. Gut. 1998;43:414–21.PubMedCrossRefGoogle Scholar
  106. 106.
    Evans JD, Cornford PA, Dodson A, et al. Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas. Pancreatology. 2001;1:254–62.PubMedCrossRefGoogle Scholar
  107. 107.
    Ciardello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008;358:1160–74.CrossRefGoogle Scholar
  108. 108.
    Bloomston M, Bhardwaj A, Ellison EC, et al. Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg. 2006;23:74–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Smeenk HG, Erdmann J, van Dekken H, et al. Long-term survival after radical resection for pancreatic head and ampullary cancer: a potential role for the EGF-R. Dig Surg. 2007;24:38–45.PubMedCrossRefGoogle Scholar
  110. 110.
    Gansauge F, Gansauge S, Schmidt E, et al. Prognostic significance of molecular alterations in human pancreatic carcinoma - an immunohistological study. Langenbecks Arch Surg. 1998;383:152–5.PubMedCrossRefGoogle Scholar
  111. 111.
    Dong M, Nio Y, Guo KJ, et al. Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer. Anticancer Res. 1998;18:4613–9.PubMedGoogle Scholar
  112. 112.
    Dallas NA, Fan F, Gray MJ, et al. Functional significance of vascular endothelial growth factor receptors on gastrointestinal cancer cells. Cancer Metastasis Rev. 2007;26:433–41.PubMedCrossRefGoogle Scholar
  113. 113.
    Seo Y, Baba H, Fukuda T, et al. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer. 2000;88:2239–45.PubMedCrossRefGoogle Scholar
  114. 114.
    Ikeda N, Nakajima Y, Sho M, et al. The association of K-ras gene mutation and vascular endothelial growth factor gene expression in pancreatic carcinoma. Cancer. 2001;92:488–99.PubMedCrossRefGoogle Scholar
  115. 115.
    Niedergethmann M, Hildenbrand R, Wostbrock B, et al. High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas. 2002;25:122–9.PubMedCrossRefGoogle Scholar
  116. 116.
    Kuwahara K, Sasaki T, Kuwada Y, et al. Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas. 2003;26:344–9.PubMedCrossRefGoogle Scholar
  117. 117.
    Farrell JJ, Elsaleh H, Garcia M, et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology. 2009;136(1):187–95.PubMedCrossRefGoogle Scholar
  118. 118.
    Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2007;33:266–70.PubMedCrossRefGoogle Scholar
  119. 119.
    Sperti C, Pasquali C, Catalini S, et al. CA 19-9 as a prognostic index after resection for pancreatic cancer. J Surg Oncol. 1993;52:137–41.PubMedCrossRefGoogle Scholar
  120. 120.
    Montgomery RC, Hoffman JP, Riley LB, et al. Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol. 1997;4:551–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Safi F, Schlosser W, Falkenreck S, et al. Prognostic value of CA 19-9 serum course in pancreatic cancer. Hepatogastroenterology. 1998;45:253–9.PubMedGoogle Scholar
  122. 122.
    Lundin J, Roberts PJ, Kuusela P, et al. The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients with pancreatic cancer. Br J Cancer. 1994;69:515–9.PubMedCrossRefGoogle Scholar
  123. 123.
    Kau SY, Shyr YM, Su CH, et al. Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers. J Am Coll Surg. 1999;188:415–20.PubMedCrossRefGoogle Scholar
  124. 124.
    Ferrone CR, Finkelstein DM, Thayer SP, et al. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.PubMedCrossRefGoogle Scholar
  125. 125.
    Duraker N, Hot S, Polat Y, et al. CEA, CA19-9 and CA125 in the differential diagnosis of benign and malignant pancreatic disease with or without jaundice. J Surg Oncol. 2007;95:142–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Kim HJ, Kim MH, Myung SJ, et al. A new strategy for the application of CA19-9 in the differentiation of pancreato-biliary cancer: analysis using a receiver operating characteristic curve. Am J Gastroenterol. 1999;94:1941–6.PubMedCrossRefGoogle Scholar
  127. 127.
    Bellone G, Turletti A, Artusio E, et al. Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients. Am J Pathol. 1999;155:537–47.PubMedCrossRefGoogle Scholar
  128. 128.
    Romano F, Uggeri F, Crippa S, et al. Immunodeficiency in different histotypes of radically operable gastrointestinal cancers. J Exp Clin Cancer Res. 2004;23:195–200.PubMedGoogle Scholar
  129. 129.
    Yamaguchi K, Noshiro H, Shimizu S, et al. Long-term and short-term survivors after pancreatectomy for pancreatic cancer. Int Surg. 2000;85:71–6.PubMedGoogle Scholar
  130. 130.
    Fogar P, Sperti C, Basso D, et al. Decreased total lymphocyte counts in pancreatic cancer: an index of adverse outcome. Pancreas. 2006;32:22–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Smith RA, Bosonnet L, Raraty M, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197(4):466–72.PubMedCrossRefGoogle Scholar
  132. 132.
    Suzuki K, Aiura K, Kitagou M, et al. Platelets counts closely correlate with the disease-free survival interval of pancreatic cancer patients. Hepatogastroenterology. 2004;51:847–53.PubMedGoogle Scholar
  133. 133.
    Brown KM, Domin C, Aranha GV, et al. Increased preoperative platelet count is associated with decreased survival after resection for adenocarcinoma of the pancreas. Am J Surg. 2005;189:278–82.PubMedCrossRefGoogle Scholar
  134. 134.
    Jamieson NB, Glen P, McMillan DC, et al. Systemic inflammatory response predicts clinical outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer. 2005;92:21–3.PubMedCrossRefGoogle Scholar
  135. 135.
    Nitecki SS, Sarr MG, Colby MG, et al. Long-term survival after resection for ductal adenocarcinoma of the pancreas: is it really improving? Ann Surg. 1995;221:59–66.PubMedCrossRefGoogle Scholar
  136. 136.
    Schneldorfer T, Ware AL, Sarr MG, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247:456–62.CrossRefGoogle Scholar
  137. 137.
    Riall TS, Cameron JL, Lillemoe KD, et al. Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery. 2006;140:746–72.CrossRefGoogle Scholar
  138. 138.
    Richter A, Niedergethmann M, Sturm JW, et al. Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25 year experience. World J Surg. 2004;27:324–9.CrossRefGoogle Scholar
  139. 139.
    Cleary SP, Gryfe R, Guindi M, et al. Prognostic factors in resected pancreatic adenocarcinoma: amalysis of actual 5-year survivors. J Am Coll Surg. 2004;198:722–31.PubMedCrossRefGoogle Scholar
  140. 140.
    Kayahara M, Nagakawa T, Ueno K, et al. An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging. Cancer. 1993;72:2118–223.PubMedCrossRefGoogle Scholar
  141. 141.
    Westerdahl J, Andren-Sandberg A, Ihse I. Recurrence of exocrine pancreatic cancer: local or hepatic? Hepatogastroenterology. 1993;40:384–7.PubMedGoogle Scholar
  142. 142.
    Sperti C, Pasquali C, Piccoli A, et al. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200.PubMedCrossRefGoogle Scholar
  143. 143.
    Hishinuma S, Ogata Y, Tomikawa M, et al. Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg. 2006;10:511–8.PubMedCrossRefGoogle Scholar
  144. 144.
    National Comprehensive Cancer Network (NCCN) Practice guidelines in oncology: pancreatic adenocarcinoma version 1 2009, 26/03/2009;http://www.nccn.org
  145. 145.
    Hermann R, Jelic S. Pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(S4):37–40.Google Scholar
  146. 146.
    Mortele KJ, Lemmerling M, de Hamptinne B, et al. Postoperative findings following the Whipple procedure. Eur Radiol. 2000;10:301–5.Google Scholar
  147. 147.
    Bluemke DA, Abrams RA, Yeo CJ, et al. Reccurrent pancreatic adenocarcinoma: spiral computed tomography evaluation following the Whipple procedure. Radiographics. 1997;17:303–13.PubMedGoogle Scholar
  148. 148.
    Casneuf V, Delrue L, Kelles A, et al. Is combined 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography superior to positron emission tomography or computed tomography alone for diagnosis, staging and restaging of pancreatic lesions? Acta Gastroenterol Belg. 2007;70(4):331–8.PubMedGoogle Scholar
  149. 149.
    Ruff J, Hänninen EL, Oettle H, et al. Detection of recurrent pancreatic cancer: comparison of FDG-PET with CT/MRI. Pancreatology. 2005;5:266–72.CrossRefGoogle Scholar
  150. 150.
    Nakamoto Y, Higashi T, Sakahara H, et al. Contribution of positron emission tomography in the detection of liver metastases from pancreatic tumours. Clin Radiol. 1999;54:248–52.PubMedCrossRefGoogle Scholar
  151. 151.
    Delbeke D, Wright PC. Pancreatic tumors: role of imaging in the diagnosis, staging and treatment. J Hepatobiliary Pancreat Surg. 2004;11:4–10.PubMedCrossRefGoogle Scholar
  152. 152.
    Morrow CE, Grage TB, Sutherland DE, et al. Hepatic resection for secondary neoplasms. Surgery. 1982;92:610–4.PubMedGoogle Scholar
  153. 153.
    Thompson HH, Tompkins RK, Longmire WP. Major hepatic resection: a 25-year experience. Ann Surg. 1983;197:375–88.PubMedCrossRefGoogle Scholar
  154. 154.
    Schildberg FW, Meyer G, Piltz S, Koebe HG. Surgical treatment of tumour metastases: general considerations and results. Surg Today. 1995;25:1–10.PubMedCrossRefGoogle Scholar
  155. 155.
    Yamada H, Hirano S, Tanaka E, et al. Surgical treatment of liver metastases from pancreatic cancer. HPB. 2006;8:85–8.PubMedCrossRefGoogle Scholar
  156. 156.
    Lindell G, Ohlsson B, Saarela A, et al. Liver resection of noncolorectal secondaries. J Surg Oncol. 1998;69:66–70.PubMedCrossRefGoogle Scholar
  157. 157.
    Elias D, de Calvacanti AA, Eggenspieler P, et al. Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients. J Am Coll Surg. 1998;187:487–93.PubMedCrossRefGoogle Scholar
  158. 158.
    Hemming AW, Sielaff TD, Gallinger S, et al. Hepatic resection of noncolorectal nonneuroendocrine metastases. Liver Transpl. 2000;6:97–101.PubMedGoogle Scholar
  159. 159.
    Dalla Valle R, Mancini C, Crafa P, et al. Pancreatic carcinoma recurrence in the remnant pancreas after a pancreaticoduodenectomy. JOP. 2006;7(5):473–7.PubMedGoogle Scholar
  160. 160.
    Takamatsu S, Ban D, Irie T, et al. Resection of a cancer developing in the remnant pancreas after a pancreaticoduodenectomy for pancreas head cancer. J Gastrointest Surg. 2005;9:263–9.PubMedCrossRefGoogle Scholar
  161. 161.
    Tajima Y, Kuroki T, Ohno T, et al. Resectable carcinoma developing in the remnant pancreas 3 years after pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas. Pancreas. 2008;36(3):325–6.CrossRefGoogle Scholar
  162. 162.
    Kleeff J, Reiser C, Hinz U, et al. Surgery for recurrent pancreatic ductal adenocarcinoma. Ann Surg. 2007;245:566–72.PubMedCrossRefGoogle Scholar
  163. 163.
    Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomised trial. J Clin Oncol. 1997;15:2403–13.PubMedGoogle Scholar
  164. 164.
    Herrmann R, Bodoky D, Ruhstaller T, et al. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007;25:2212–7.PubMedCrossRefGoogle Scholar
  165. 165.
    Sultana A, Tudur-Smith C, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol. 2007;25:2607–15.PubMedCrossRefGoogle Scholar
  166. 166.
    Kozuch P, Grossbard ML, Barzdins A, et al. Irinotecan combined with gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (G-FLIP) is an effective and non crossresistant treatment for chemotherapy refractory metastatic pancreatic cancer. Oncologist. 2001;6:488–95.PubMedCrossRefGoogle Scholar
  167. 167.
    Cantore M, Rabbi C, Fiorentini G, et al. Combined irinotecan and oxalipatin in patients with advanced pre-treated pancreatic cancer. Oncology. 2004;67:93–7.PubMedCrossRefGoogle Scholar
  168. 168.
    Ulrich-Pur H, Raderer M, Kornek GV, et al. Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced adenocarcinoma. Br J Cancer. 2003;88:1180–4.PubMedCrossRefGoogle Scholar
  169. 169.
    Reni M, Pasetto L, Aprile G, et al. Raltitrexed-eloxatin salvage chemotherapy in gemcitabine resistant metastatic pancreatic cancer. Br J Cancer. 2006;94:785–91.PubMedCrossRefGoogle Scholar
  170. 170.
    Sultana A, Tudur-Smith C, Cunningham D, et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/ combined modality therapy. Br J Cancer. 2007;96:1183–90.PubMedCrossRefGoogle Scholar
  171. 171.
    Stocken DD, Hassan AB, Altman DG, et al. Modelling prognostic factors in advanced pancreatic cancer. Br J Cancer. 2008;99:883–93.PubMedCrossRefGoogle Scholar
  172. 172.
    Müller MW, Friess H, Könninger J, et al. Factors influencing survival after bypass procedures in patients with advanced pancreatic adenocarcinomas. Am J Surg. 2008;195:221–8.PubMedCrossRefGoogle Scholar
  173. 173.
    Glen P, Jamieson NB, McMillan DC, et al. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.PubMedCrossRefGoogle Scholar
  174. 174.
    Zabora J, Brintzenhofeszoc K, Curbow B, et al. The prevalence of psychological distress by cancer site. Psychooncology. 2001;10:19–28.PubMedCrossRefGoogle Scholar
  175. 175.
    Verschuur EM, Steyerberg EW, Kuipers EJ, et al. Follow-up after surgical treatment for cancer of the gastrointestinal tract. Dig Liver Dis. 2006;38:479–84.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 2013

Authors and Affiliations

  • Richard A. Smith
    • 1
  • Jane V. Butler
    • 1
  • John P. Neoptolemos
    • 1
    Email author
  1. 1.Division of Surgery and OncologyThe Owen and Ellen Evans Chair of Cancer Studies, School of Cancer Studies, Royal Liverpool University Hospital, University of LiverpoolLiverpoolUK

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