Skip to main content
Erschienen in: International Journal of Clinical Oncology 4/2018

24.03.2018 | Original Article

D-dimer predicts postoperative recurrence and prognosis in patients with liver metastasis of colorectal cancer

verfasst von: Akira Watanabe, Kenichiro Araki, Norihumi Harimoto, Norio Kubo, Takamichi Igarashi, Norihiro Ishii, Takahiro Yamanaka, Kei Hagiwara, Hiroyuki Kuwano, Ken Shirabe

Erschienen in: International Journal of Clinical Oncology | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Colorectal cancer is common, and its incidence is increasing throughout the world. The liver is a major metastatic site, and colorectal liver metastasis (CRLM) has a poor prognosis. Although liver resection is the most effective therapy for CRLM, postoperative recurrence is common. Thus, prognostic markers for CRLM are greatly needed. D-dimer, a fibrin cleavage product, has been shown to be related to colorectal tumor progression, and is also associated with malignant progression and recurrence in various cancers. Therefore, we evaluated the value of D-dimer in predicting the prognosis in CRLM.

Methods

We retrospectively evaluated 90 cases of resected CRLM to determine the correlation between D-dimer and patient survival. The cut-off value for D-dimer levels was determined using receiver operating characteristic curve analysis.

Results

Significant differences occurred in the recurrence group with higher D-dimer levels (P = 0.00736*), while the optimal cut-off value was 0.6 µg/mL. High D-dimer levels (≥ 0.6 µg/mL) were associated with poor recurrence-free survival (RFS; P = 0.0000841*) and cancer-specific survival (CSS; P = 0.00615*). In the multivariate analysis, D-dimer correlated with CRLM prognosis and independently predicted RFS (P = 0.0179*).

Conclusion

High D-dimer levels were associated with poor RFS and CSS. D-dimer was an independent prognostic factor of RFS. Therefore, D-dimer may help predict recurrence and prognosis in patients with CRLM.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Zurück zum Zitat McNally SJ, Parks RW (2013) Surgery for colorectal liver metastases. Dig Surg 30(4–6):337–347CrossRefPubMed McNally SJ, Parks RW (2013) Surgery for colorectal liver metastases. Dig Surg 30(4–6):337–347CrossRefPubMed
3.
Zurück zum Zitat Simmonds PC, Primrose JN, Colquitt JL et al (2006) Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer 94(7):982–999CrossRefPubMedPubMedCentral Simmonds PC, Primrose JN, Colquitt JL et al (2006) Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer 94(7):982–999CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Fong Y, Fortner J, Sun RL et al (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 230(3):309–318 (discussion 318–321) CrossRefPubMedPubMedCentral Fong Y, Fortner J, Sun RL et al (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 230(3):309–318 (discussion 318–321) CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Nagashima I, Takada T, Adachi M et al (2006) Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. World J Gastroenterol 12(39):6305–6309CrossRefPubMedPubMedCentral Nagashima I, Takada T, Adachi M et al (2006) Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. World J Gastroenterol 12(39):6305–6309CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Pulivarthi S, Gurram MK (2014) Effectiveness of d-dimer as a screening test for venous thromboembolism: an update. N Am J Med Sci 6(10):491–499CrossRefPubMedPubMedCentral Pulivarthi S, Gurram MK (2014) Effectiveness of d-dimer as a screening test for venous thromboembolism: an update. N Am J Med Sci 6(10):491–499CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Motavaf E, Sunesen KG, Stender MT et al (2014) Prognostic value of preoperative D-dimer and carcinoembryonic antigen levels in patients undergoing intended curative resection for colorectal cancer: a prospective cohort study. Int J Colorectal Dis 29(11):1427–1432CrossRefPubMed Motavaf E, Sunesen KG, Stender MT et al (2014) Prognostic value of preoperative D-dimer and carcinoembryonic antigen levels in patients undergoing intended curative resection for colorectal cancer: a prospective cohort study. Int J Colorectal Dis 29(11):1427–1432CrossRefPubMed
8.
Zurück zum Zitat Yamamoto M, Yoshinaga K, Matsuyama A et al (2012) Plasma D-dimer level as a mortality predictor in patients with advanced or recurrent colorectal cancer. Oncology 83(1):10–15CrossRefPubMed Yamamoto M, Yoshinaga K, Matsuyama A et al (2012) Plasma D-dimer level as a mortality predictor in patients with advanced or recurrent colorectal cancer. Oncology 83(1):10–15CrossRefPubMed
9.
Zurück zum Zitat Zhou YX, Yang ZM, Feng J et al (2013) High plasma D-dimer level is associated with decreased survival in patients with lung cancer: a meta-analysis. Tumour Biol 34(6):3701–3704CrossRefPubMed Zhou YX, Yang ZM, Feng J et al (2013) High plasma D-dimer level is associated with decreased survival in patients with lung cancer: a meta-analysis. Tumour Biol 34(6):3701–3704CrossRefPubMed
10.
Zurück zum Zitat Ma X, Li Y, Zhang J et al (2014) Prognostic role of D-dimer in patients with lung cancer: a meta-analysis. Tumour Biol 35(3):2103–2109CrossRefPubMed Ma X, Li Y, Zhang J et al (2014) Prognostic role of D-dimer in patients with lung cancer: a meta-analysis. Tumour Biol 35(3):2103–2109CrossRefPubMed
11.
Zurück zum Zitat Khoury JD, Adcock DM, Chan F et al (2010) Increases in quantitative D-dimer levels correlate with progressive disease better than circulating tumor cell counts in patients with refractory prostate cancer. Am J Clin Pathol 134(6):964–969CrossRefPubMed Khoury JD, Adcock DM, Chan F et al (2010) Increases in quantitative D-dimer levels correlate with progressive disease better than circulating tumor cell counts in patients with refractory prostate cancer. Am J Clin Pathol 134(6):964–969CrossRefPubMed
12.
Zurück zum Zitat Go SI, Lee MJ, Lee WS et al (2015) D-dimer can serve as a prognostic and predictive biomarker for metastatic gastric cancer treated by chemotherapy. Med (Baltimore) 94(30):e951CrossRef Go SI, Lee MJ, Lee WS et al (2015) D-dimer can serve as a prognostic and predictive biomarker for metastatic gastric cancer treated by chemotherapy. Med (Baltimore) 94(30):e951CrossRef
13.
Zurück zum Zitat Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458CrossRefPubMed Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458CrossRefPubMed
14.
Zurück zum Zitat Zacharski LR, Wojtukiewicz MZ, Costantini V et al (1992) Pathways of coagulation/fibrinolysis activation in malignancy. Semin Thromb Hemost 18(1):104–116CrossRefPubMed Zacharski LR, Wojtukiewicz MZ, Costantini V et al (1992) Pathways of coagulation/fibrinolysis activation in malignancy. Semin Thromb Hemost 18(1):104–116CrossRefPubMed
15.
Zurück zum Zitat Caine GJ, Lip GY, Stonelake PS et al (2004) Platelet activation, coagulation and angiogenesis in breast and prostate carcinoma. Thromb Haemost 92(1):185–190PubMed Caine GJ, Lip GY, Stonelake PS et al (2004) Platelet activation, coagulation and angiogenesis in breast and prostate carcinoma. Thromb Haemost 92(1):185–190PubMed
16.
Zurück zum Zitat Mytnik M, Stasko J (2011) D-dimer, plasminogen activator inhibitor-1, prothrombin fragments and protein C—role in prothrombotic state of colorectal cancer. Neoplasma 58(3):235–238CrossRefPubMed Mytnik M, Stasko J (2011) D-dimer, plasminogen activator inhibitor-1, prothrombin fragments and protein C—role in prothrombotic state of colorectal cancer. Neoplasma 58(3):235–238CrossRefPubMed
17.
Zurück zum Zitat Edwards CM, Warren J, Armstrong L et al (1993) D-dimer: a useful marker of disease stage in surgery for colorectal cancer. Br J Surg 80(11):1404–1405CrossRefPubMed Edwards CM, Warren J, Armstrong L et al (1993) D-dimer: a useful marker of disease stage in surgery for colorectal cancer. Br J Surg 80(11):1404–1405CrossRefPubMed
18.
Zurück zum Zitat Kilic M, Yoldas O, Keskek M et al (2008) Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis 10(3):238–241CrossRefPubMed Kilic M, Yoldas O, Keskek M et al (2008) Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis 10(3):238–241CrossRefPubMed
19.
Zurück zum Zitat Xu G, Zhang YL, Huang W (2004) Relationship between plasma D-dimer levels and clinicopathologic parameters in resectable colorectal cancer patients. World J Gastroenterol 10(6):922–923CrossRefPubMedPubMedCentral Xu G, Zhang YL, Huang W (2004) Relationship between plasma D-dimer levels and clinicopathologic parameters in resectable colorectal cancer patients. World J Gastroenterol 10(6):922–923CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat 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(1):77–82CrossRefPubMed 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(1):77–82CrossRefPubMed
21.
Zurück zum Zitat Oya M, Akiyama Y, Yanagida T et al (1998) Plasma D-dimer level in patients with colorectal cancer: its role as a tumor marker. Surg Today 28(4):373–378CrossRefPubMed Oya M, Akiyama Y, Yanagida T et al (1998) Plasma D-dimer level in patients with colorectal cancer: its role as a tumor marker. Surg Today 28(4):373–378CrossRefPubMed
22.
Zurück zum Zitat Mochizuki S, Yoshino T, Kojima T et al (2010) Therapeutic significance of a D-dimer cut-off level of > 3 microg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab. Jpn J Clin Oncol 40(10):933–937CrossRefPubMed Mochizuki S, Yoshino T, Kojima T et al (2010) Therapeutic significance of a D-dimer cut-off level of > 3 microg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab. Jpn J Clin Oncol 40(10):933–937CrossRefPubMed
23.
Zurück zum Zitat Beppu T, Sakamoto Y, Hasegawa K et al (2012) A nomogram predicting disease-free survival in patients with colorectal liver metastases treated with hepatic resection: multicenter data collection as a Project Study for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 19(1):72–84CrossRefPubMed Beppu T, Sakamoto Y, Hasegawa K et al (2012) A nomogram predicting disease-free survival in patients with colorectal liver metastases treated with hepatic resection: multicenter data collection as a Project Study for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 19(1):72–84CrossRefPubMed
24.
Zurück zum Zitat Inanc M, Er O, Karaca H et al (2013) D-dimer is a marker of response to chemotherapy in patients with metastatic colorectal cancer. J BUON 18(2):391–397PubMed Inanc M, Er O, Karaca H et al (2013) D-dimer is a marker of response to chemotherapy in patients with metastatic colorectal cancer. J BUON 18(2):391–397PubMed
25.
Zurück zum Zitat Zhu L, Liu B, Zhao Y et al (2014) High levels of D-dimer correlated with disease status and poor prognosis of inoperable metastatic colorectal cancer patients treated with bevacizumab. J Cancer Res Ther 10(Suppl):246–251CrossRefPubMed Zhu L, Liu B, Zhao Y et al (2014) High levels of D-dimer correlated with disease status and poor prognosis of inoperable metastatic colorectal cancer patients treated with bevacizumab. J Cancer Res Ther 10(Suppl):246–251CrossRefPubMed
26.
Zurück zum Zitat Tomimaru Y, Yano M, Takachi K et al (2008) Correlation between pretherapeutic d-dimer levels and response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. Dis Esophagus 21(4):281–287CrossRefPubMed Tomimaru Y, Yano M, Takachi K et al (2008) Correlation between pretherapeutic d-dimer levels and response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. Dis Esophagus 21(4):281–287CrossRefPubMed
27.
Zurück zum Zitat Dirix LY, Vermeulen PB, Pawinski A et al (1997) Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients. Br J Cancer 76(2):238–243CrossRefPubMedPubMedCentral Dirix LY, Vermeulen PB, Pawinski A et al (1997) Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients. Br J Cancer 76(2):238–243CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Sakamoto Y, Miyamoto Y, Beppu T et al (2015) Post-chemotherapeutic CEA and CA19-9 are prognostic factors in patients with colorectal liver metastases treated with hepatic resection after oxaliplatin-based chemotherapy. Anticancer Res 35(4):2359–2368PubMed Sakamoto Y, Miyamoto Y, Beppu T et al (2015) Post-chemotherapeutic CEA and CA19-9 are prognostic factors in patients with colorectal liver metastases treated with hepatic resection after oxaliplatin-based chemotherapy. Anticancer Res 35(4):2359–2368PubMed
29.
Zurück zum Zitat Zhang D, Yu M, Xu T et al (2013) Predictive value of serum CEA, CA19-9 and CA125 in diagnosis of colorectal liver metastasis in Chinese population. Hepatogastroenterology 60(126):1297–1301PubMed Zhang D, Yu M, Xu T et al (2013) Predictive value of serum CEA, CA19-9 and CA125 in diagnosis of colorectal liver metastasis in Chinese population. Hepatogastroenterology 60(126):1297–1301PubMed
30.
Zurück zum Zitat Loupakis F, Yang D, Yau L et al (2015) Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107(3):pii: dju427CrossRef Loupakis F, Yang D, Yau L et al (2015) Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107(3):pii: dju427CrossRef
31.
Zurück zum Zitat Shen H, Yang J, Huang Q et al (2015) Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol 21(21):6470–6478CrossRefPubMedPubMedCentral Shen H, Yang J, Huang Q et al (2015) Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol 21(21):6470–6478CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Kirwan CC, Clarke AC, Howell SJ et al (2016) PO-31—circulating tumour cells and hypercoagulability: a lethal relationship in metastatic breast cancer. Thromb Res 140(Suppl 1):S188CrossRefPubMed Kirwan CC, Clarke AC, Howell SJ et al (2016) PO-31—circulating tumour cells and hypercoagulability: a lethal relationship in metastatic breast cancer. Thromb Res 140(Suppl 1):S188CrossRefPubMed
33.
Zurück zum Zitat Seeberg LT, Brunborg C, Waage A et al (2017) Survival impact of primary tumor lymph node status and circulating tumor cells in patients with colorectal liver metastases. Ann Surg Oncol 24(8):2113–2121CrossRefPubMedPubMedCentral Seeberg LT, Brunborg C, Waage A et al (2017) Survival impact of primary tumor lymph node status and circulating tumor cells in patients with colorectal liver metastases. Ann Surg Oncol 24(8):2113–2121CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Zhao R, Cai Z, Li S et al (2017) Expression and clinical relevance of epithelial and mesenchymal markers in circulating tumor cells from colorectal cancer. Oncotarget 8(6):9293–9302PubMed Zhao R, Cai Z, Li S et al (2017) Expression and clinical relevance of epithelial and mesenchymal markers in circulating tumor cells from colorectal cancer. Oncotarget 8(6):9293–9302PubMed
35.
Zurück zum Zitat Tieken C, Versteeg HH (2016) Anticoagulants versus cancer. Thromb Res 140(Suppl 1):S148–S153CrossRefPubMed Tieken C, Versteeg HH (2016) Anticoagulants versus cancer. Thromb Res 140(Suppl 1):S148–S153CrossRefPubMed
36.
Zurück zum Zitat Klerk CP, Smorenburg SM, Otten HM et al (2005) The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 23(10):2130–2135CrossRefPubMed Klerk CP, Smorenburg SM, Otten HM et al (2005) The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 23(10):2130–2135CrossRefPubMed
37.
Zurück zum Zitat van Doormaal FF, Di Nisio M, Otten HM et al (2011) Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol 29(15):2071–2076CrossRefPubMed van Doormaal FF, Di Nisio M, Otten HM et al (2011) Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol 29(15):2071–2076CrossRefPubMed
38.
Zurück zum Zitat Rothwell PM, Wilson M, Elwin CE et al (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376(9754):1741–1750CrossRefPubMed Rothwell PM, Wilson M, Elwin CE et al (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376(9754):1741–1750CrossRefPubMed
Metadaten
Titel
D-dimer predicts postoperative recurrence and prognosis in patients with liver metastasis of colorectal cancer
verfasst von
Akira Watanabe
Kenichiro Araki
Norihumi Harimoto
Norio Kubo
Takamichi Igarashi
Norihiro Ishii
Takahiro Yamanaka
Kei Hagiwara
Hiroyuki Kuwano
Ken Shirabe
Publikationsdatum
24.03.2018
Verlag
Springer Japan
Erschienen in
International Journal of Clinical Oncology / Ausgabe 4/2018
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-018-1271-x

Weitere Artikel der Ausgabe 4/2018

International Journal of Clinical Oncology 4/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.