Abstract
Purpose
Hyperfibrinogenemia is associated with poor prognosis in various cancers; however, its clinical relevance in gastric cancer has not been well analyzed. We conducted this study to assess the clinicopathological significance and prognostic value of hyperfibrinogenemia in patients with gastric cancer.
Methods
Plasma fibrinogen levels were measured preoperatively in 315 patients undergoing surgery for gastric cancer. We then evaluated the clinicopathological significance of hyperfibrinogenemia and its relationship with several biomarkers, including white blood cell (WBC), C-reactive protein (CRP), platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Postoperative plasma levels were compared with preoperative levels. The multivariate prognostic value of hyperfibrinogenemia was calculated using the Cox proportional hazards model.
Results
Tumor progression was significantly associated with hyperfibrinogenemia, as were the CRP level and platelet counts. Plasma fibrinogen levels decreased significantly after radical surgery. Adjusting for TNM factors, multivariate analysis indicated that hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio = 2.607, 95 % confidence interval = 1.180–5.761, P = 0.018).
Conclusion
Preoperative hyperfibrinogenemia was associated with tumor progression, inflammatory mediators, and poor overall survival in patients with gastric cancer.
Similar content being viewed by others
References
Brown LF, Van de Water L, Harvey VS, Dvorak HE. Fibrinogen influx and accumulation of cross-linked fibrin in healing wounds and in tumor stroma. Am J Pathol. 1988;130:455–65.
Matsuda S, Takeuchi H, Kawakubo H, Fukuda K, Nakamura R, Takahashi T, et al. Cumulative prognostic scores based on plasma fibrinogen and serum albumin levels in esophageal cancer patients treated with transthoracic esophagectomy: comparison with the Glasgow prognostic score. Ann Surg Oncol. 2015;22:302–10.
Qi Q, Geng Y, Sun M, Chen H, Wang P, Chen Z. Hyperfibrinogen is associated with the systemic inflammatory response and predicts poor prognosis in advanced pancreatic cancer. Pancreas. 2015;44:977–82.
Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. Elevated plasma fibrinogen levels are associated with a poor prognosis in patients with hepatocellular carcinoma. Oncology. 2013;85:269–77.
Liu YL, Lu Q, Liang JW, et al. High plasma fibrinogen is correlated with poor response to trastumab treatment in HER2 positive breast cancer Liang B. Medicine (Baltimore). 2015;94:e481.
Son HJ, Park JW, Chang HJ, Kim DY, Kim BC, Kim SY, Park SC, Choi HS, Oh JH. Preoperative plasma hyperfibrinogenemia is predictive of poor prognosis in patients with nonmetastatic colon cancer. Ann Surg Oncol. 2013;20:2908–13.
Thurner EM, Krenn-Pilko S, Langsenlehner U, Stojakovic T, Pichler M, Gerger A, et al. The association of an elevated plasma fibrinogen level with cancer-specific and overall survival in prostate cancer. World J Urol. 2015;33:1467–73.
Rickles FR, Hancock WW, Edwards RL, Zacharski LR. Antimetastatic agents. I. Role of cellular procoagulants in the pathogenesis of fibrin deposition in cancer and the use of anticoagulants and/or antiplatelet drugs in cancer treatment. Semin Thromb Hemost. 1988;14:88–94.
Hogg N. Human monocytes have prothrombin cleaving activity. Clin Exp Immunol. 1983;53:725–30.
Yamashita H, Kitayama J, Nagawa H, Yatomi Y, Nagawa H. Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol. 2005;35:595–600.
Lee SE, Lee JH, Ryu KW, Nam BH, Cho SJ, Lee JY, et al. Preoperative plasma fibrinogen level is a useful predictor of adjacent organ involvement in patients with advanced gastric cancer. J Gastric Cancer. 2012;12:81–7.
Japanese classification of gastric carcinoma. 3rd English edition. Gastric Cancer. 2011;14:101–12.
http://www.sekisuimedical.jp/english/business/diagnostics/blood/fbg/index.html.
Kanai M, Okumura N, Tozuka M, Yatomi Y. 34 ed. Rinshou Kensahou Teiyou. Kanehara. 2015; p. 402.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’for medical statistics. Bone Marrow Transplant. 2013;48:452–8.
Yamaguchi T, Yamamoto Y, Yokota S, Nakagawa M, Ito M, Ogura T. Involvement of interleukin-6 in the elevation of plasma fibrinogen levels in lung cancer patients. Jpn J Clin Oncol. 1998;28:740–4.
Hu C, Chen R, Chen W, Pang W, Xue X, Zhu G, Shen X. Thrombocytosis is a significant indictor of hypercoagulability, prognosis and recurrence in gastric cancer. Exp Ther Med. 2014;8:125–32.
Zhao L, Feng S, Huang S, Tong Y, Chen Z, Wu P et al. Diagnostic value of hyperfibrinogenemia as a predictive factor for appendiceal perforation in acute appendicitis. ANZ J Surg. 2015. doi: 10.1111/ans.13316.
Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2015. doi:10.1007/s00595-015-1236-x/.
Acknowledgments
This work was partly supported by JSPS KAKENHI Grant Number 15K10117.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
We have no conflicts of interest to declare.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Suzuki, T., Shimada, H., Nanami, T. et al. Hyperfibrinogenemia is associated with inflammatory mediators and poor prognosis in patients with gastric cancer. Surg Today 46, 1394–1401 (2016). https://doi.org/10.1007/s00595-016-1339-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00595-016-1339-z