Top

International Journal of Colorectal Disease

Published in:

01-11-2014 | Original Article

Prognostic value of preoperative d-dimer and carcinoembryonic antigen levels in patients undergoing intended curative resection for colorectal cancer: a prospective cohort study

Authors: Ehsan Motavaf, Kåre Gotschalck Sunesen, Mogens Tornby Stender, Ole Thorlacius-Ussing

Published in: International Journal of Colorectal Disease | Issue 11/2014

Abstract

Purpose

Carcinoembryonic antigen (CEA) has limited value as an isolated predictor for survival among colorectal cancer (CRC) patients. d-dimer (DD) is a strong predictor of survival among metastatic CRC patients, but the prognostic value in non-metastatic CRC patients remains controversial. We examined the prognostic value of preoperative DD levels in relation to CEA levels in non-metastatic, resectable CRC patients.

Methods

Between October 2003 and November 2005, 166 patients were included. We used the Kaplan-Meier method to compute 5-year mortality rates, stratified by preoperative DD and CEA levels. Adjusted Cox regression analysis was used to compute mortality rate ratios (MRRs) during postoperative years 0–1 and 1–5 based on the preoperative CEA and DD levels.

Results

The cumulative 5-year mortality rate was 15 % (95 % confidence interval [CI], 9–25 %) in patients with normal DD and CEA levels, 30 % (CI, 16–53 %) in patients with isolated elevated CEA levels, 37 % (CI, 25–53 %) in patients with isolated elevated DD levels, and 60 % (CI, 37–83 %) in patients with elevated CEA and DD levels. Elevated CEA was associated with an approximately ten-fold increase in mortality within the first postoperative year (adjusted MRR 9.8, CI 2.5–38.3); this association was lost during postoperative years 1–5 (adjusted MRR 1.1, CI 0.5–2.7). Elevated DD was associated with a greater than two-fold increase in mortality during postoperative years 0–1 (adjusted MRR 2.8, CI 0.7–11.0) and 1–5 (adjusted MRR 2.2, CI 1.1–4.8).

Conclusion

DD is a strong predictor of survival among non-metastatic curatively resected CRC patients, particularly in combination with CEA.

Katoh H, Yamashita K, Kokuba Y et al (2008) Diminishing impact of preoperative carcinoembryonic antigen (CEA) in prognosis of Dukes’ C colorectal cancer. Anticancer Res 28:1933–1941PubMed

Yamashita K, Watanabe M (2009) Clinical significance of tumor markers and an emerging perspective on colorectal cancer. Cancer Sci 100:195–199. doi:10.1111/j.1349-7006.2008.01022.x PubMedCrossRef

Duffy MJ, van Dalen A, Haglund C et al (2007) Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer 43:1348–1360. doi:10.1016/j.ejca.2007.03.021 PubMedCrossRef

Locker GY, Hamilton S, Harris J et al (2006) ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 24:5313–5327. doi:10.1200/JCO.2006.08.2644 PubMedCrossRef

Kilic M, Yoldas O, Keskek M et al (2008) Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Color Dis 10:238–241. doi:10.1111/j.1463-1318.2007.01374.x CrossRef

Stender MT, Larsen TB, Sørensen HT, Thorlacius-Ussing O (2012) Preoperative plasma D-dimer predicts 1-year survival in colorectal cancer patients with absence of venous thromboembolism (VTE): a prospective clinical cohort study. J Thromb Haemost 10:2027–2031. doi:10.1111/j.1538-7836.2012.04887.x PubMedCrossRef

Oya M, Akiyama Y, Okuyama T, Ishikawa H (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 31:388–394PubMedCrossRef

Ay C, Dunkler D, Pirker R et al (2012) High D-dimer levels are associated with poor prognosis in cancer patients. Haematologica 97:1158–1164. doi:10.3324/haematol.2011.054718 PubMedCrossRefPubMedCentral

Knowlson L, Bacchu S, Paneesha S et al (2010) Elevated D-dimers are also a marker of underlying malignancy and increased mortality in the absence of venous thromboembolism. J Clin Pathol 63:818–822. doi:10.1136/jcp.2010.076349 PubMedCrossRef

10.

Hoke M, Dieckmann K, Koppensteiner R et al (2011) Prognostic value of plasma d-dimer levels in patients with glioblastoma multiforme—results from a pilot study. Wien Klin Wochenschr 123:199–203. doi:10.1007/s00508-011-1556-9 PubMedCrossRef

11.

Ay C, Vormittag R, Dunkler D et al (2009) D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 27:4124–4129. doi:10.1200/JCO.2008.21.7752 PubMedCrossRef

12.

Batschauer AP, Figueiredo CP, Bueno EC et al (2010) D-dimer as a possible prognostic marker of operable hormone receptor-negative breast cancer. Ann Oncol 21:1267–1272. doi:10.1093/annonc/mdp474

13.

Kwon H-C, Oh SY, Lee S et al (2008) Plasma levels of prothrombin fragment F1 + 2, D-dimer and prothrombin time correlate with clinical stage and lymph node metastasis in operable gastric cancer patients. Jpn J Clin Oncol 38:2–7. doi:10.1093/jjco/hym157 PubMedCrossRef

14.

Xu G, Zhang Y, Huang W (2004) Relationship between plasma D-dimer levels and clinicopathologic parameters in resectable colorectal cancer patients. World J Gastroenterol 10:922–923PubMed

15.

Lee AY (2002) Cancer and thromboembolic disease: pathogenic mechanisms. Cancer Treat Rev 28:137–140. doi:10.1016/S0305-7372(02)00044-0 PubMedCrossRef

16.

Danish Colorectal Cancer Group (2005) annual report

17.

Stender MT, Frøkjaer JB, Larsen TB et al (2009) Preoperative plasma D-dimer is a predictor of postoperative deep venous thrombosis in colorectal cancer patients: a clinical, prospective cohort study with 1-year follow-up. Dis Colon Rectum 52:446–451. doi:10.1007/DCR.0b013e318197e2b2 PubMedCrossRef

18.

Edge SB, Byrd DR, Compton CC, Fritx AG, Greene FL et al (2010) AJCC cancer staging manual, 7th edn. NY Springer, New York

19.

Jespersen J, Bertina RM HF (1999) Laboratory techniques in Thrombosis. A manual, 2nd revised edition of ECAT assay procedures. Kluwer Academic, Dordecht/Boston/London

20.

Grann AF, Erichsen R, Nielsen AG et al (2011) Existing data sources for clinical epidemiology: the clinical laboratory information system (LABKA) research database at Aarhus University, Denmark. Clin Epidemiol 3:133–138. doi:10.2147/CLEP.S17901 PubMedCrossRefPubMedCentral

21.

Stevens DP, Mackay IR (1973) Increased carcinoembryonic antigen in heavy cigarette smokers. Lancet 2:1238–1239PubMedCrossRef

22.

Bjerner J, Høgetveit A, Wold Akselberg K et al (2008) Reference intervals for carcinoembryonic antigen (CEA), CA125, MUC1, alfa-foeto-protein (AFP), neuron-specific enolase (NSE) and CA19.9 from the NORIP study. Scand J Clin Lab Invest 68:703–713. doi:10.1080/00365510802126836 PubMedCrossRef

23.

Blackwell K, Hurwitz H, Liebérman 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 101:77–82. doi:10.1002/cncr.20336 PubMedCrossRef

24.

Pedrazzani C, Cerullo G, Marrelli D et al (2010) Is circulating D-dimer level a better prognostic indicator than CEA in resectable colorectal cancer? Our experience on 199 cases. Int J Biol Markers 25:171–176PubMed

25.

O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 96:1420–1425. doi:10.1093/jnci/djh275 PubMedCrossRef

26.

Salluh JIF, Rabello LSCF, Rosolem MM et al (2011) The impact of coagulation parameters on the outcomes of patients with severe community-acquired pneumonia requiring intensive care unit admission. J Crit Care 26:496–501. doi:10.1016/j.jcrc.2011.02.001 PubMedCrossRef

27.

Maeda K, Hirota M, Ichihara A et al (2006) Applicability of disseminated intravascular coagulation parameters in the assessment of the severity of acute pancreatitis. Pancreas 32:87–92PubMedCrossRef

28.

Morange PE, Bickel C, Nicaud V et al (2006) Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study. Arterioscler Thromb Vasc Biol 26:2793–2799. doi:10.1161/01.ATV.0000249406.92992.0d PubMedCrossRef

29.

Folsom AR, Delaney JA, Lutsey PL et al (2009) Associations of factor VIIIc, D-dimer, and plasmin-antiplasmin with incident cardiovascular disease and all-cause mortality. Am J Hematol 84:349–353. doi:10.1002/ajh.21429

30.

Di Castelnuovo A, de Curtis A, Costanzo S et al (2013) Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study. Haematologica 98:1476–1480. doi:10.3324/haematol.2012.083410 PubMedCrossRefPubMedCentral

31.

Dempfle CE, Zips S, Ergül H, Heene DL (2001) The fibrin assay comparison trial (FACT): evaluation of 23 quantitative D-dimer assays as basis for the development of D-dimer calibrators. FACT study group. Thromb Haemost 85:671–678PubMed

32.

Bülow S, Christensen H (2005) Retningslinier for diagnostik og behandling af colorectal cancer

Title: Prognostic value of preoperative d-dimer and carcinoembryonic antigen levels in patients undergoing intended curative resection for colorectal cancer: a prospective cohort study
Authors: Ehsan Motavaf
Kåre Gotschalck Sunesen
Mogens Tornby Stender
Ole Thorlacius-Ussing
Publication date: 01-11-2014
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 11/2014
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-014-2000-1

2024 ASCO Annual Meeting

Springer Medicine

Prognostic value of preoperative d-dimer and carcinoembryonic antigen levels in patients undergoing intended curative resection for colorectal cancer: a prospective cohort study

Abstract

Purpose

Methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2014

Development and validation of a practical score to predict pain after excisional hemorrhoidectomy

Acute lower gastrointestinal bleeding originating from an arteriovenous fistula of superior rectal artery

Anorectal manometric parameters are influenced by gender and age in subjects with normal bowel function

Ultrapure alginate gel reduces adhesion reformation after adhesiolysis

Endothelin and vascular remodelling in colitis pathogenesis—Appendicitis and appendectomy limit colitis by suppressing endothelin pathways

Survival after acute colon diverticulitis treated in hospital