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Clinical and Translational Oncology

, Volume 7, Issue 5, pp 189–197 | Cite as

Exocrine pancreatic cancer: Symptoms at presentation and their relation to tumour site and stage

  • Miquel Porta
  • Xavier Fabregat
  • Núria Malats
  • Luisa Guarner
  • Alfredo Carrato
  • Ana de Miguel
  • Laura Ruiz
  • Manuel Jariod
  • Sergi Costafreda
  • Susana Coll
  • Juan Alguacil
  • Josep M. Corominas
  • Ricard Solà
  • Antonio Salas
  • Francisco X. Real
  • the PANKRAS II Study Group
Original Articles

Abstract

Introduction. The need to detect pancreatic cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with exocrine pancreatic cancer and evaluated their association with clinical characteristics such as tumour site and disease stage.

Patients and methods. All patients (n=185) with exocrine pancreatic cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 3 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission.

Results. At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p<0.001). At presentation, the most frequent symptoms were asthenia (86%), anorexia (83%), weight-loss (85%), abdominal pain (79%), and choluria (59%). Cholestatic symptoms were more common in tumours affecting only the pancreatic head (p<0.001). There was a clear trend towards more localized tumours with increasing numbers of cholestatic signs (p<0.001). Asthenia, anorexia and weight-loss were unrelated to stage. An increased symptom-to-diagnosis interval was associated with more advanced stage (p=0.048).

Conclusions. Proper attention to signs and symptoms, especially cholestasis, may help identify patients with pancreatic cancer at an earlier stage. Results also provide a current picture of the semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.

Key words

pancreatic neoplasms/diagnosis pancreatic neoplasms/epidemiology signs and symptoms diagnosis cholestasis jaundice cachexia pruritis pain/diagnosis presentation stage choluria asthenia anorexia weight-loss constitutional syndrome epigastric mass proteomics 

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References

  1. 1.
    Porta M, Malats N, Jariod M, et al. Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. Lancet. 1999;354:2125–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363:1049–57.PubMedCrossRefGoogle Scholar
  3. 3.
    Weiderpass E, Partanen T, Kaaks R, et al. Pancreatic cancer: Occurrence, trends, and environmental etiology. A review. Scand J Work Environ Health. 1999;24:165–74.Google Scholar
  4. 4.
    Ekbom A, Hunter D. Pancreatic cancer. In: Adami HO, Hunter D, Trichopoulos D, editors. Textbook of Cancer Epidemiology. New York: Oxford University Press; 2002. p. 233–47.Google Scholar
  5. 5.
    Anderson KE, Potter JD, Mack TM. Pancreatic cancer. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer Epidemiology and Prevention. New York: Oxford University Press; 1996. p. 725–71.Google Scholar
  6. 6.
    Lowenfels AB, Maisonneuve P. Pancreatic cancer: development of a unifying etiologic concept. In: Löhr JM, Colcher D, Hallingswirth MA, Liebe S. Cell and molecular biology of pancreatic carcinoma. Recent developments in research and experimental therapy. Ann New York Acad Sci. 1999;880:191–200.CrossRefGoogle Scholar
  7. 7.
    Hart AR. Pancreatic cancer: any prospects for prevention? Postgrad Med J. 1999;75:521–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Trede M, Carter DC. Clinical evaluation and preoperative assessment. In: Trede M, Carter DC, editors. Surgery of the pancreas. New York: Churchill Livingstone; 1997. p. 459–70.Google Scholar
  9. 9.
    Fearon KCH, Wigmore SJ, Carter DC. Chemotherapy and radiotherapy in the treatment of pancreatic cancer. In: Trede M, Carter DC, editors. Surgery of the pancreas. New York: Churchill Livingstone; 1997. p. 551–62.Google Scholar
  10. 10.
    DiMagno EP, Reber HA, Tempero MA (American Gastroenterological Association Clinical Practice and Practice Economics Committee). American Gastroenterological Association medical position statement: epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. Gastroenterology. 1999;117:1463–84.CrossRefGoogle Scholar
  11. 11.
    Rothenberg ML, Abbruzzese JL, Moore M, Portenoy RK, Robertson JM, Wanebo HJ. A rationale for expanding the endpoints for clinical trials in advanced pancreatic carcinoma. Cancer. 1996;78 Suppl 3:627–32.Google Scholar
  12. 12.
    Levin B. An overview of preventive strategies for pancreatic cancer. Ann Oncol. 1999;10 Suppl 4:S193–6.CrossRefGoogle Scholar
  13. 13.
    Anonymous. Early diagnosis and screening for pancreatic cancer [editorial]. Lancet. 1986;2:783–4.Google Scholar
  14. 14.
    DiMagno EP. Pancreatic cancer: clinical presentation, pitfalls and early clues. Ann Oncol. 1999;10 Supl 4:140–2.PubMedCrossRefGoogle Scholar
  15. 15.
    Gullo L, Tomassetti P, Migliori M, Casadei R, Marrano D. Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis? Pancreas. 2001;22:210–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Beger HG, Warshaw AL, Büchler MW, et al, editors. The pancreas. Oxford: Blackwell; 1998.Google Scholar
  17. 17.
    Howard JM, Idezuki Y, Ihse I, Prinz RA, editors. Surgical diseases of the pancreas. 3rd. ed. Baltimore: Williams and Wilkins; 1998.Google Scholar
  18. 18.
    Neoptolemos J, Lemoine NR, editors. Pancreatic cancer. Molecular and clinical advances. Oxford: Blackwell; 1996.Google Scholar
  19. 19.
    Go VLW, DiMagno EP, Gardner JD, Lebenthal E, Reber HA, Scheele GA, editors. The pancreas. Biology, pathobiology, and disease. 2nd. ed. New York: Raven; 1993.Google Scholar
  20. 20.
    Falk J, Keidan R, Rigo PK, Dmuchowski C. Adenocarcinoma of the pancreatic head: a community teaching hospital’s experience from 1982 to 1992. Am Surg. 1999;65:15–8.PubMedGoogle Scholar
  21. 21.
    Faivre J, Forman D, Estève J, Obradovic M, San M and the EUROCARE Working Group. Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. Eur J Cancer. 1998;34:2184–90.CrossRefGoogle Scholar
  22. 22.
    Gudjonsson B. Carcinoma of the pancreas: critical analysis of costs, results of resections, and the need for standardized reporting. J Am Coll Surg. 1995;181:483–503.PubMedGoogle Scholar
  23. 23.
    Gordon TA, Burleyson GP, Tielsch JM, Cameron JL. The effects of regionalization on cost and outcome for one general high-risk surgical procedure. Ann Surg. 1995;221:43–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Real FX. A “catastrophic hypothesis” for pancreas cancer progression. Gastroenterology. 2003;124:1958–64.PubMedCrossRefGoogle Scholar
  25. 25.
    Maguire A, Porta M, Malats N, Gallén M, Piñol JL, Fernández E. Cancer survival and the duration of symptoms. An analysis of possible forms of the risk function. Eur J Cancer. 1994;30A:785–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Richter JM. Clinical assessment of pancreatic cancer. In: Beger HG, Warshaw AL, Büchler MW, et al, editors. The pancreas. Vol. 2. Oxford: Blackwell; 1998. p. 950–2.Google Scholar
  27. 27.
    Modolell I, Guarner L, Malagelada JR. Vagaries of clinical presentation of pancreatic and biliary tract cancer. Ann Oncol. 1999;10 Supl 4:82–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Lankisch PG. Clinical evaluation. En: Beger HG, Warshaw AL, Büchler MW, et al, editors. The pancreas. Vol. 1. Oxford: Blackwell; 1998. p. 163–8.Google Scholar
  29. 29.
    Casper ES. Pancreatic cancer: How can we progress? [editorial]. Eur J Cancer. 1993;29A:171–2.PubMedCrossRefGoogle Scholar
  30. 30.
    Gapstur SM, Gann P. Is pancreatic cancer a preventable disease? [editorial]. JAMA. 2001;286:967–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Zeiderman MR, Wyman A, Euinton HA, Simms JM, Rogers K. Diagnostic difficulties in patients with a pancreatic mass. BMJ. 1991;302:1395–6.PubMedGoogle Scholar
  32. 32.
    Cancer of the Pancreas Task Force. Staging of cancer of the pancreas. Cancer. 1981;47:1631–7.CrossRefGoogle Scholar
  33. 33.
    Bakkevold KE, Arnesjo B, Kambestad B. Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial. Scand J Gastroenterol. 1992;27:317–25.PubMedGoogle Scholar
  34. 34.
    Maringhini A, Ciambra M, Raimondo M, et al. Clinical presentation and ultrasonography in the diagnosis of pancreatic cancer. Pancreas. 1993;8:146–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Ridder GJ, Klempnauer J. Back pain in patients with ductal pancreatic cancer. Its impact on resectability and prognosis after resection. Scand J Gastroenterol. 1995;30:1216–20.PubMedGoogle Scholar
  36. 36.
    Kelsen DP, Portenoy RK, Thaler HT, et al. Pain and depression in patients with newly diagnosed pancreas cancer. J Clin Oncol. 1995;13:748–55.PubMedGoogle Scholar
  37. 37.
    Halder SL, McBeth J, Silman AJ, Thompson DG, Macfarlane GJ. Psychosocial risk factors for the onset of abdominal pain. Results from a large prospective population-based study. Int J Epidemiol. 2002;31:1219–25.PubMedCrossRefGoogle Scholar
  38. 38.
    Fernández E, Porta M, Malats N, Belloc J, Gallén M. Symptom to diagnosis interval and survival in cancers of the digestive tract. Dig Dis Sci. 2002;47:2434–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Tishelman C, Taube A, Sachs L. Self-reported symptom distress in cancer patients: reflections of disease, illness or sickness? Soc Sci Med. 1991;33:1229–40.PubMedCrossRefGoogle Scholar
  40. 40.
    Petricoin EF, Zoon KC, Kohn EC, Barrett JC, Liotta LA. Clinical proteomics: translating benchside promise into bedside reality. Nat Rev Drug Discov. 2002;1:683–95.PubMedCrossRefGoogle Scholar
  41. 41.
    Wulfkuhle JD, Liotta LA, Petricoin EF. Early detection: Proteomic applications for the early detection of cancer. Nat Rev Cancer. 2003;3:267–75.PubMedCrossRefGoogle Scholar
  42. 42.
    Petricoin EF, Liotta LA. SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer. Curr Opin Biotechnol. 2004;15:24–30.PubMedCrossRefGoogle Scholar
  43. 43.
    Porta M, Fernández E, Alguacil J. Semiology, proteomics and the early detection of symptomatic cancer. J Clin Epidemiol. 2003;56:815–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Diamandis EP. Analysis of serum proteomic patterns for early cancer diagnosis: drawing attention to potential problems. J Natl Cancer Inst. 2004;96:353–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Ransohoff DF. Rules of evidence for cancer molecular-marker discovery and validation. Nat Rev Cancer. 2004;4:309–14.PubMedCrossRefGoogle Scholar
  46. 46.
    Feinstein AR. Misguided efforts and future challenges for research on “diagnostic tests”. J Epidemiol Community Health. 2002;56:330–2.PubMedCrossRefGoogle Scholar
  47. 47.
    Rockhill B. Proteomic patterns in serum and identification of ovarian cancer. Lancet. 2002;360:169.PubMedCrossRefGoogle Scholar
  48. 48.
    Porta M, Malats N, Guarner L, et al. Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. J Epidemiol Community Health. 1999;53:702–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Porta M, Jariod M, Malats N, et al. Prevalence of K-ras mutations at diagnosis and serum levels of DDT, DDE, PCBs and other organochlorine compounds in exocrine pancreatic cancer. In: Gress TM, editor. Molecular pathogenesis of pancreatic cancer. Amsterdam: IOS Press; 2000. p. 37–44.Google Scholar
  50. 50.
    Porta M, Costafreda S, Malats N, et al. Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology. Eur J Epidemiol. 2000;16:533–41.PubMedCrossRefGoogle Scholar
  51. 51.
    Soler M, Malats N, Porta M, et al. Medical conditions in patients with pancreatic and biliary diseases: validity and agreement between data from questionnaires and medical records. Dig Dis Sci. 1999;44:2469–77.PubMedCrossRefGoogle Scholar
  52. 52.
    Alguacil J, Porta M, Benavides FG, et al. Occupation and pancreatic cancer in Spain: a case-control study based on job titles. Int J Epidemiol. 2000;29:1004–13.PubMedCrossRefGoogle Scholar
  53. 53.
    Alguacil J, Kauppinen T, Porta M, et al. Risk of pancreatic cancer and occupational exposures in Spain. Ann Occupat Hyg. 2000;44:391–403.Google Scholar
  54. 54.
    Malats N, Casals T, Porta M, Guarner L, Estivill X, Real FX. The cystic fibrosis transmembrane regulator (CFTR) DF508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreas cancer. Gut. 2001;48:70–4.PubMedCrossRefGoogle Scholar
  55. 55.
    Real FX, Malats N, Lesca G, et al. Family history of cancer and germline BRCA2 mutations in sporadic exocrine pancreas cancer. Gut. 2002;50:653–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Alguacil J, Porta M, Malats N, et al. Occupational exposure to organic solvents and K-ras mutations in exocrine pancreatic cancer. Carcinogenesis. 2002;23:101–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Alguacil J, Porta M, Kauppinen T, Malats N, Kogevinas M, Carrato A. Occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons and other agents and K-ras activation in human exocrine pancreatic cancer. Int J Cancer. 2003;107:635–41.PubMedCrossRefGoogle Scholar
  58. 58.
    Gavaldà L, Porta M, Malats N, et al. Agreement between information supplied by the patient and a family member on medical history, consumption of tobacco, alcohol and coffee, and diet in cancer of the exocrine pancreas and extrahepatic biliary system. Gac Sanit. 1995;9:334–42.PubMedGoogle Scholar
  59. 59.
    International Classification of Diseases, Clinical Modification. 9th revision. Ann Arbor, MI: Commission on Professional and Hospital Activities; 1980.Google Scholar
  60. 60.
    International Union Against Cancer. TNM classification of malignant tumours. 4th ed., 2nd revision. Berlin: Springer; 1992.Google Scholar
  61. 61.
    American Joint Committee on Cancer, TNM Committee of the International Union Against Cancer. Handbook for staging of cancer from the Manual for Staging of Cancer. 4th ed. Philadelphia: J.B. Lippincott; 1993.Google Scholar
  62. 62.
    World Health Organization. International Classification of Diseases for Oncology (ICD-O-2). 2nd ed. Geneva: World Health Organization; 1990.Google Scholar
  63. 63.
    Berg JW. Morphologic classification of human cancer. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer Epidemiology and Prevention. 2nd ed. New York: Oxford University Press; 1996. p. 28–44.Google Scholar
  64. 64.
    Armitage P, Berry G. Statistical Methods in Medical Research. 2nd ed. Oxford: Blackwell; 1987. p. 125–32, 205–9.Google Scholar
  65. 65.
    Schlesselman JJ, Stolley PD. Case-control Studies. New York: Oxford University Press; 1982. p. 174–7.Google Scholar
  66. 66.
    Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic Research. Belmont, CA: Lifetime Learning Publications; 1982. p. 343.Google Scholar
  67. 67.
    Bland M. An Introduction to Medical Statistics. Oxford: Oxford Medical Publications; 1987. p. 241–65.Google Scholar
  68. 68.
    Okusaka T, Okada S, Ueno H, et al. Abdominal pain in patients with resectable pancreatic cancer with reference to clinicopathologic findings. Pancreas. 2001;22:279–84.PubMedCrossRefGoogle Scholar
  69. 69.
    Passik SD, Breitbart WS. Depression in patients with pancreatic carcinoma: Diagnostic and treatment issues. Cancer. 1996;78:615–26.Google Scholar
  70. 70.
    Porta M. Role of organochlorine compounds in the etiology of pancreatic cancer: A proposal to develop methodological standards. Epidemiology. 2001;12:272–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Porta M, Zumeta E, Ruiz L, et al. Persistent toxic substances and public health in Spain. Int J Occupat Environ Health. 2003;9:112–7.Google Scholar
  72. 72.
    Porta M, Kogevinas M, Zumeta E, et al. Concentraciones de compuestos tóxicos persistentes en la población española: el rompecabezas sin piezas y la protección de la salud pública. Gac Sanit. 2002;16:257–66.PubMedGoogle Scholar
  73. 73.
    Porta M, Malats N, Belloc J, Gallén M, Fernández E. Do we believe what patients say about their neoplastic symptoms? An analysis of factors that influence the interviewer’s judgement. Eur J Epidemiol. 1996;12:553–62.CrossRefGoogle Scholar
  74. 74.
    Malats N, Belloc J, Gallén M, Porta M. Disagreement between hospital medical records and a structured patient interview on the type and date of the first symptom in cancers of the digestive tract. Rev Épidémiol Santé Publique. 1995;43:533–40.PubMedGoogle Scholar
  75. 75.
    Nebril BA, Filgueira LT, Calvo AP, et al. Importance of surgical staging in patients with cancer of the exocrine pancreas. Rev Esp Enferm Dig. 1993;83:447–52.Google Scholar
  76. 76.
    Cubiella J, Castells A, Fondevila C, et al. Prognostic factors in nonresectable pancreatic adenocarcinoma: A rationale to design therapeutic trials. Am J Gastroenterol. 1999;94:1271–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Sáenz A, Kuriansky J, Salvador L, et al. Thoracoscopic splanchnicectomy for pain control in patients with unresectable carcinoma of the pancreas. Surg Endosc. 2000;14:717–20.PubMedCrossRefGoogle Scholar
  78. 78.
    Mercadante S, Catala E, Arcuri E, et al. Celiac plexus block for pancreatic cancer pain: Factors influencing pain, symptoms and quality of life. J Pain Symptom Manage. 2003;26:1140–7.PubMedCrossRefGoogle Scholar

Copyright information

© FESEO 2005

Authors and Affiliations

  • Miquel Porta
    • 1
  • Xavier Fabregat
    • 1
    • 2
  • Núria Malats
    • 1
  • Luisa Guarner
    • 3
  • Alfredo Carrato
    • 4
  • Ana de Miguel
    • 4
  • Laura Ruiz
    • 1
  • Manuel Jariod
    • 1
  • Sergi Costafreda
    • 1
  • Susana Coll
    • 5
  • Juan Alguacil
    • 1
  • Josep M. Corominas
    • 1
    • 6
  • Ricard Solà
    • 1
    • 5
  • Antonio Salas
    • 7
  • Francisco X. Real
    • 1
    • 8
  • the PANKRAS II Study Group
  1. 1.Unidad de Epidemiología Clínica y Molecular del Cáncer. Instituto Municipal de Investigación MédicaUniversidad Autónoma de BarcelonaBarcelonaSpain
  2. 2.Departamento de OncologíaHospital del MarBarcelonaSpain
  3. 3.Departamento de GastroenterologíaHospital Vall d’HebronBarcelonaSpain
  4. 4.Departamento de OncologíaHospital Universitario de Elche. Universidad Miguel HernándezAlicanteSpain
  5. 5.Departamento de GastroenterologíaHospital del MarBarcelonaSpain
  6. 6.Departamento de PatologíaHospital del MarBarcelonaSpain
  7. 7.Departamento de PatologíaHospital Mútua de TerrassaTerrassa. BarcelonaSpain
  8. 8.Universidad Pompeu FabraBarcelonaSpain

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