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Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC).

Methods

Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes.

Results

Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019).

Conclusions

The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.

    Article  PubMed  Google Scholar 

  2. Kanda M, Shimizu D, Tanaka H, et al. Metastatic pathway-specific transcriptome analysis identifies MFSD4 as a putative tumor suppressor and biomarker for hepatic metastasis in patients with gastric cancer. Oncotarget. 2016;7:13667–79.

    PubMed  PubMed Central  Google Scholar 

  3. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet. 2009;374:477–90.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kanda M, Murotani K, Kobayashi D, et al. Postoperative adjuvant chemotherapy with S-1 alters recurrence patterns and prognostic factors among patients with stage II/III gastric cancer: a propensity score matching analysis. Surgery. 2015;158:1573–80.

    Article  PubMed  Google Scholar 

  5. Shen L, Shan YS, Hu HM, et al. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol. 2013;14:e535–47.

    Article  PubMed  Google Scholar 

  6. Kanda M, Kobayashi D, Tanaka C, et al. Adverse prognostic impact of perioperative allogeneic transfusion on patients with stage II/III gastric cancer. Gastric Cancer. 2016;19:255–63.

    Article  CAS  PubMed  Google Scholar 

  7. Chen WH, Tang LQ, Wang FW, et al. Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma. BMC Cancer. 2014;14:583.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Falanga A, Panova-Noeva M, Russo L. Procoagulant mechanisms in tumour cells. Best Pract Res Clin Haematol. 2009;22:49–60.

    Article  CAS  PubMed  Google Scholar 

  9. Gil-Bernabe AM, Lucotti S, Muschel RJ. Coagulation and metastasis: what does the experimental literature tell us? Br J Haematol. 2013;162:433–41.

    Article  CAS  PubMed  Google Scholar 

  10. Diao D, Wang Z, Cheng Y, et al. D-dimer: not just an indicator of venous thrombosis but a predictor of asymptomatic hematogenous metastasis in gastric cancer patients. PLoS One. 2014;9:e101125.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kilic M, Yoldas O, Keskek M, et al. Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis. 2008;10:238–41.

    Article  CAS  PubMed  Google Scholar 

  12. Batschauer AP, Figueiredo CP, Bueno EC, et al. D-dimer as a possible prognostic marker of operable hormone receptor-negative breast cancer. Ann Oncol. 2010;21:1267–72.

    Article  CAS  PubMed  Google Scholar 

  13. Sobin LH, Gospodarowicz MK, Wittekind C. International Union Against Cancer, TNM classification of malignant tumors. 7th ed. New York: Wiley-Blackwell; 2009.

    Google Scholar 

  14. Kanda M, Shimizu D, Fujii T, et al. Function and diagnostic value of Anosmin-1 in gastric cancer progression. Int J Cancer. 2016;138:721–30.

    Article  CAS  PubMed  Google Scholar 

  15. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113–23.

    Article  Google Scholar 

  16. Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93.

    Article  CAS  PubMed  Google Scholar 

  17. Kanda M, Kodera Y, Sakamoto J. Updated evidence on adjuvant treatments for gastric cancer. Expert Rev Gastroenterol Hepatol. 2015;9(12):1549–60.

    Article  PubMed  Google Scholar 

  18. Schirren R, Reim D, Novotny AR. Adjuvant and/or neoadjuvant therapy for gastric cancer? A perspective review. Ther Adv Med Oncol. 2015;7:39–48.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kanda M, Shimizu D, Nomoto S, et al. Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer. Gastric Cancer. 2015;18:288–96.

    Article  CAS  PubMed  Google Scholar 

  20. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.

    Article  PubMed  Google Scholar 

  21. Kanda M, Nomoto S, Oya H, et al. The expression of melanoma-associated antigen D2 both in surgically resected and serum samples serves as clinically relevant biomarker of gastric cancer progression. Ann Surg Oncol. 2016;23 Suppl 2:214–21.

    Article  Google Scholar 

  22. Samama MM, Horellou MH, Elalamy I, Mathieux V, Ombandza-Moussa E, Conard J. D-dimer levels, constitutional thrombophilia, and venous thrombosis prediction: clinical aspects and implications. Semin Vasc Med. 2005;5:371–4.

    Article  CAS  PubMed  Google Scholar 

  23. Yang SD, Liu H, Sun YP, et al. Prevalence and risk factors of deep vein thrombosis in patients after spine surgery: a retrospective case-cohort study. Sci Rep. 2015;5:11834.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Teke Z, Sacar M, Yenisey C, Atalay AO, Bicakci T, Erdem E. Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model. Am J Surg. 2008;196:774–87.

    Article  CAS  PubMed  Google Scholar 

  25. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11:123–34.

    Article  CAS  PubMed  Google Scholar 

  26. Palumbo JS, Talmage KE, Massari JV, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood. 2005;105:178–85.

    Article  CAS  PubMed  Google Scholar 

  27. Liu P, Zhu Y, Liu L. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma. Onco Targets Ther. 2015;8:1335–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Go SI, Lee MJ, Lee WS, et al. D-dimer can serve as a prognostic and predictive biomarker for metastatic gastric cancer treated by chemotherapy. Medicine (Baltimore). 2015;94:e951.

    Article  CAS  Google Scholar 

  29. Kanda M, Mizuno A, Fujii T, et al. Tumor infiltrative pattern predicts sites of recurrence after curative gastrectomy for stages 2 and 3 gastric cancer. Ann Surg Oncol. 2016;23:1934–40.

    Article  PubMed  Google Scholar 

  30. Blackwell K, Haroon Z, Broadwater G, et al. Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status. J Clin Oncol. 2000;18:600–8.

    CAS  PubMed  Google Scholar 

  31. Kasthuri RS, Taubman MB, Mackman N. Role of tissue factor in cancer. J Clin Oncol. 2009;27:4834–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bertagnolli MM, Eagle CJ, Zauber AG, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84.

    Article  CAS  PubMed  Google Scholar 

  33. Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69:7775–83.

    Article  CAS  PubMed  Google Scholar 

  34. Stewart CA, Vivier E, Colonna M. Strategies of natural killer cell recognition and signaling. Curr Top Microbiol Immunol. 2006;298:1–21.

    CAS  PubMed  Google Scholar 

  35. Im JH, Fu W, Wang H, et al. Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res. 2004;64:8613–9.

    Article  CAS  PubMed  Google Scholar 

  36. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20:576–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Palumbo JS, Kombrinck KW, Drew AF, et al. Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood. 2000;96:3302–9.

    CAS  PubMed  Google Scholar 

  38. Chiang AC, Massague J. Molecular basis of metastasis. N Engl J Med. 2008;359:2814–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Coupland LA, Chong BH, Parish CR. Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. Cancer Res. 2012;72:4662–71.

    Article  CAS  PubMed  Google Scholar 

  40. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379:1591–601.

    Article  CAS  PubMed  Google Scholar 

  41. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–80.

    Article  CAS  PubMed  Google Scholar 

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Disclosures

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Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan

    Mitsuro Kanda MD, PhD, FACS, Chie Tanaka MD, PhD, Daisuke Kobayashi MD, PhD, Akira Mizuno MD, Yuri Tanaka MD, Hideki Takami MD, PhD, Naoki Iwata MD, PhD, Masamichi Hayashi MD, PhD, Yukiko Niwa MD, PhD, Suguru Yamada MD, PhD, FACS, Tsutomu Fujii MD, PhD, FACS, Hiroyuki Sugimoto MD, PhD, Michitaka Fujiwara MD, PhD & Yasuhiro Kodera MD, PhD, FACS

  2. Center for Clinical Research, Aichi Medical University, Nagakute, Japan

    Kenta Murotani PhD

Authors
  1. Mitsuro Kanda MD, PhD, FACS
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  2. Chie Tanaka MD, PhD
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  3. Daisuke Kobayashi MD, PhD
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  4. Akira Mizuno MD
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  6. Hideki Takami MD, PhD
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  8. Masamichi Hayashi MD, PhD
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  10. Suguru Yamada MD, PhD, FACS
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  11. Tsutomu Fujii MD, PhD, FACS
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  14. Michitaka Fujiwara MD, PhD
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  15. Yasuhiro Kodera MD, PhD, FACS
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Corresponding author

Correspondence to Mitsuro Kanda MD, PhD, FACS.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2016_5544_MOESM1_ESM.tif

Survival analyses according to the Coagulation Score when patients with the Score of 1 are subdivided. a. Overall survival. b. Recurrence-free survival (TIFF 5194 kb)

Impact of the Coagulation Score on recurrence-free survival according to pathological nodal status (TIFF 5194 kb)

Supplementary material 3 (DOCX 19 kb)

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Kanda, M., Tanaka, C., Kobayashi, D. et al. Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer. Ann Surg Oncol 24, 502–509 (2017). https://doi.org/10.1245/s10434-016-5544-1

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  • DOI: https://doi.org/10.1245/s10434-016-5544-1

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