World Journal of Surgery

, 33:1298 | Cite as

Effect of Preoperative Hyperfibrinogenemia on Recurrence of Colorectal Cancer Without a Systemic Inflammatory Response

  • Hiroharu Yamashita
  • Joji Kitayama
  • Masataka Taguri
  • Hirokazu Nagawa



Disorders in the blood coagulation system are often associated with malignancy. Patients with colorectal cancer (CRC) have been shown to have abnormal data for various coagulation tests.


We retrospectively analyzed the relation between the preoperative plasma fibrinogen level and tumor recurrence in 569 patients with CRC who underwent curative surgical resection and were followed up without adjuvant chemotherapy.


The plasma fibrinogen level showed a positive association with tumor recurrence, age, sex, T stage, and TNM classification. When divided with the median value, hyperfibrinogenemia is positively correlated with tumor recurrence, although it lost independence in the multivariate analysis. In the C-reactive protein (CRP)-negative population, hyperfibrinogenemia is independently correlated with tumor recurrence and recurrence-free survival. In contrast, hyperfibrinogenemia has no effect on recurrence in CRP-positive patients.


Hyperfibrinogenemia is clinically relevant in tumor recurrence before a systemic inflammatory response and thus can be a useful predictor of recurrence in the preinflammatory stage of CRC.


Fibrinogen Tumor Recurrence Plasma Fibrinogen Level Ciprofibrate Fibrinogen Degradation Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan and by a grant from the Ministry of Health and Welfare of Japan.


  1. 1.
    Sakamoto J, Ohashi Y, Hamada C et al (2004) Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from three randomized trials. J Clin Oncol 22:484–492PubMedGoogle Scholar
  2. 2.
    Laurie JA, Moertel CG, Fleming TR et al (1989) Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil: the North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol 7:1447–1456PubMedGoogle Scholar
  3. 3.
    Akasu T, Moriya Y, Ohashi Y et al (2006) Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial. Jpn J Clin Oncol 36:237–244PubMedCrossRefGoogle Scholar
  4. 4.
    Moertel CG, Fleming TR, Macdonald JS et al (1995) Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 122:321–326PubMedGoogle Scholar
  5. 5.
    Chu DZ, Erickson CA, Russell MP et al (1991) Prognostic significance of carcinoembryonic antigen in colorectal carcinoma: serum levels before and after resection and before recurrence. Arch Surg 126:314–316PubMedGoogle Scholar
  6. 6.
    Wolmark N, Fisher B, Wieand HS et al (1984) The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer: results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg 199:375–382PubMedCrossRefGoogle Scholar
  7. 7.
    Wang WS, Lin JK, Chiou TJ et al (2000) Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience. Jpn J Clin Oncol 30:12–16PubMedCrossRefGoogle Scholar
  8. 8.
    Louhimo J, Carpelan-Holmstrom M, Alfthan H et al (2002) Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer. Int J Cancer 101:545–548PubMedCrossRefGoogle Scholar
  9. 9.
    Harrison LE, Guillem JG, Paty P et al (1997) Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients. J Am Coll Surg 185:55–59PubMedGoogle Scholar
  10. 10.
    Wanebo HJ, Rao B, Pinsky CM et al (1978) Preoperative carcinoembryonic antigen level as a prognostic indicator in colorectal cancer. N Engl J Med 299:448–451PubMedGoogle Scholar
  11. 11.
    Takahashi T, Kato T, Kodaira S et al (1996) Prognostic factors of colorectal cancer: results of multivariate analysis of curative resection cases with or without adjuvant chemotherapy. Am J Clin Oncol 19:408–415PubMedCrossRefGoogle Scholar
  12. 12.
    Yamashita H, Kitayama J, Nagawa H (2005) Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol 35:595–600PubMedCrossRefGoogle Scholar
  13. 13.
    Yamashita H, Kitayama J, Kanno N et al (2006) Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer 6:147PubMedCrossRefGoogle Scholar
  14. 14.
    Chen Z, Malhotra PS, Thomas GR et al (1999) Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 5:1369–1379PubMedGoogle Scholar
  15. 15.
    Palumbo JS, Kombrinck KW, Drew AF et al (2000) Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood 96:3302–3309PubMedGoogle Scholar
  16. 16.
    Palumbo JS, Potter JM, Kaplan LS et al (2002) Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res 62:6966–6972PubMedGoogle Scholar
  17. 17.
    Costantini V, Zacharski LR, Moritz TE et al (1990) The platelet count in carcinoma of the lung and colon. Thromb Haemost 64:501–505PubMedGoogle Scholar
  18. 18.
    Oya M, Akiyama Y, Okuyama T et al (2001) High preoperative plasma D-dimer level is associated with advanced tumor stage and short survival after curative resection in patients with colorectal cancer. Jpn J Clin Oncol 31:388–394PubMedCrossRefGoogle Scholar
  19. 19.
    Abbasciano V, Bianchi MP, Trevisani L et al (1995) Platelet activation and fibrinolysis in large bowel cancer. Oncology 52:381–384PubMedCrossRefGoogle Scholar
  20. 20.
    Iversen LH, Thorlacius-Ussing O (2002) Relationship of coagulation test abnormalities to tumour burden and postoperative DVT in resected colorectal cancer. Thromb Haemost 87:402–408PubMedGoogle Scholar
  21. 21.
    Blackwell K, Hurwitz H, Lieberman G et al (2004) Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma. Cancer 101:77–82PubMedCrossRefGoogle Scholar
  22. 22.
    Wang Q, Xie R, Zhang QY (2005) Clinical significance of plasma fibrinogen level in patients with colorectal cancer. Zhonghua Zhong Liu Za Zhi 27:544–546PubMedGoogle Scholar
  23. 23.
    Nozoe T, Matsumata T, Kitamura M et al (1998) Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer. Am J Surg 176:335–338PubMedCrossRefGoogle Scholar
  24. 24.
    Shimada H, Kitabayashi H, Nabeya Y et al (2003) Treatment response and prognosis of patients after recurrence of esophageal cancer. Surgery 133:24–31PubMedCrossRefGoogle Scholar
  25. 25.
    Nakanishi H, Araki N, Kudawara I et al (2002) Clinical implications of serum C-reactive protein levels in malignant fibrous histiocytoma. Int J Cancer 99:167–170PubMedCrossRefGoogle Scholar
  26. 26.
    Stamatiadis AP, St. Toumanidou M, Vyssoulis GP et al (1990) Value of serum acute-phase reactant proteins and carcinoembryonic antigen in the preoperative staging of colorectal cancer: a multivariate analysis. Cancer 65:2055–2057PubMedCrossRefGoogle Scholar
  27. 27.
    Chung YC, Chang YF (2003) Serum C-reactive protein correlates with survival in colorectal cancer patients but is not an independent prognostic indicator. Eur J Gastroenterol Hepatol 15:369–373PubMedCrossRefGoogle Scholar
  28. 28.
    McMillan DC, Canna K, McArdle CS (2003) Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg 90:215–219PubMedCrossRefGoogle Scholar
  29. 29.
    Black S, Kushner I, Samols D (2004) C-reactive protein. J Biol Chem 279:48487–48490PubMedCrossRefGoogle Scholar
  30. 30.
    Poynter JN, Gruber SB, Higgins PD et al (2005) Statins and the risk of colorectal cancer. N Engl J Med 352:2184–2192PubMedCrossRefGoogle Scholar
  31. 31.
    Kleemann R, Gervois PP, Verschuren L et al (2003) Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation. Blood 101:545–551PubMedCrossRefGoogle Scholar
  32. 32.
    Palumbo JS, Talmage KE, Massari JV et al (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105:178–185PubMedCrossRefGoogle Scholar
  33. 33.
    Yano H, Kitayama J, Hatano K et al (2001) Clustered cancer cells show a distinct adhesion behavior from single cell form under physiological shear conditions. J Exp Clin Cancer Res 20:407–412Google Scholar
  34. 34.
    Nieswandt B, Hafner M, Echtenacher B et al (1999) Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res 59:1295–1300PubMedGoogle Scholar
  35. 35.
    Gale AJ, Gordon SG (2001) Update on tumor cell procoagulant factors. Acta Haematol 106:25–32PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2009

Authors and Affiliations

  • Hiroharu Yamashita
    • 1
  • Joji Kitayama
    • 1
  • Masataka Taguri
    • 2
  • Hirokazu Nagawa
    • 1
  1. 1.Department of Surgical OncologyThe University of Tokyo, Graduate School of MedicineTokyoJapan
  2. 2.Department of BiostatisticsThe University of Tokyo, Graduate School of MedicineTokyoJapan

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