Pretreatment Plasma Fibrinogen Levels Research Articles

Elevated Plasma Fibrinogen Levels Are Associated with a Poor Prognosis in Patients with Hepatocellular Carcinoma

Objectives: Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in cancer patients. We investigated the prognostic value of pretreatment plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC). Methods: One hundred and thirteen patients with newly diagnosed HCC were retrospectively evaluated. We investigated the correlation between pretreatment plasma fibrinogen levels, clinicopathological parameters and overall survival. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with overall survival. Results: The median value of the pretreatment plasma fibrinogen level was 279 mg/dl. Elevated plasma fibrinogen levels were associated with larger tumor size, the presence of vascular invasion and higher Cancer Liver Italian Program scores. Lower plasma fibrinogen levels were associated with higher Child-Pugh grades. The overall survival rates in patients with pretreatment plasma fibrinogen levels ≥315 mg/dl were significantly lower than those with a pretreatment plasma fibrinogen level <315 mg/dl (p = 0.016). On multivariate analysis, the plasma fibrinogen levels (per 100 mg/dl) were found to be independently associated with overall survival (hazard ratio 1.236; p = 0.046). Conclusions: This study demonstrates that elevated pretreatment plasma fibrinogen levels are associated with tumor progression and are independently associated with a poor prognosis in patients with HCC.

The pretreatment platelet and plasma fibrinogen level correlate with tumor progression and metastasis in patients with pancreatic cancer

Cancer patients frequently present with activated coagulation pathways and thrombocytosis, which are potentially associated with tumor progression and prognosis. However, the prognostic value of abnormal plasma fibrinogen and platelet levels for the treatment of pancreatic cancer is unclear. The purpose of our study was to evaluate the prognostic value of plasma fibrinogen and platelet levels in pancreatic cancer, and to devise a prognostic model to identify the patients with greatest risk for a poor overall survival. One hundred and twenty-five patients diagnosed with pancreatic ductal adenocarcinoma in our hospital between May 2000 and June 2005 were included in this study. The plasma fibrinogen and platelet levels were examined before treatment and analyzed along with patient clinicopathological parameters and overall survival. The foundation of prognostic model was based on the risk factors according to the Cox proportional hazard model. The incidence of hyperfibrinogenemia and thrombocytosis was 24.8% (31/125) and 15.2% (19/125), respectively. The mean fibrinogen concentration differed significantly between the early (I/II) and late (III/IV) stage patients (3.19 ± 0.70 vs. 3.65 ± 0.90 g/l, p = 0.008). Patients with a higher concentration of plasma fibrinogen and platelets had a worse prognosis (p < 0.05). There also existed a significant correlation between higher fibrinogen/platelet levels and distant organ metastasis (p < 0.05, respectively). Bivariate correlation analysis showed that plasma fibrinogen levels correlated significantly with platelet levels (p = 0.000). Multivariate analysis revealed that pretreatment plasma fibrinogen levels (p = 0.027), tumor stage (p = 0.026) and distant metastasis (p = 0.027) were independent prognostic factors. The median survival time for the low-, intermediate-, and high-risk groups was 9.6 months (95% CI 6.2–13.0), 3.8 months (95% CI 2.3–5.3), and 2.3 months (95% CI 0.9–3.7), respectively (p = 0.000). Pretreatment plasma fibrinogen and platelet levels closely correlated with tumor progression, metastasis and overall survival in pancreatic cancer. The foundation of prognostic model may help us identify the greatest risk populations with pancreatic cancer.

Clinical significance of plasma fibrinogen level as a predictive marker for postoperative recurrence of esophageal squamous cell carcinoma in patients receiving neoadjuvant treatment

Among multidisciplinary therapies developed for advanced esophageal cancer, neoadjuvant chemotherapy and chemoradiotherapy have been established as standard treatments. To deliver cautious follow up and intense treatment for high-risk patients, a simple and instructive biomarker for the postoperative recurrence needs to be identified. Fibrinogen, a common component of hemostasis, has been suggested to not only play an important role in cancer metastasis, but also correlate with tumor recurrence. We aim to clarify the validity of plasma fibrinogen as a marker for predicting the postoperative recurrence of esophageal squamous cell carcinoma patients who received neoadjuvant treatment. We reviewed 72 consecutive patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy at the Keio University Hospital from 2001 to 2010. Of them, we retrospectively examined 68 patients who underwent plasma fibrinogen examination before and after neoadjuvant treatment and underwent transthoracic radical esophagectomy. We investigated patient characteristics, clinicopathological factors, neoadjuvant treatment effects, postoperative course, and plasma fibrinogen levels. We investigated pretreatment and preoperative (postneoadjuvant treatment) plasma fibrinogen levels, as well as changes in fibrinogen levels before and after neoadjuvant treatment. Patients with preoperative hyperfibrinogenemia (>350 mg/dL) and patients with increased plasma fibrinogen levels during neoadjuvant treatment showed significantly shorter postoperative disease-free survival (DFS) (P = 0.002 and P = 0.037, respectively). Moreover, we classified these patients into three classes on the basis of their preoperative fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment. Patients who had both high preoperative plasma fibrinogen and increased fibrinogen levels showed significantly shorter DFS than others. In contrast, patients who had normal preoperative plasma fibrinogen and decreased fibrinogen levels showed significantly longer DFS. Based on this fibrinogen classification, we could differentiate between significantly favorable and poor prognosis patients group. Overall, this classification (hazard ratio = 1.812, P = 0.013) and the response to neoadjuvant treatment (hazard ratio = 0.350, P = 0.007) were found to be significant determining factors for postoperative DFS. With the validity of preoperative plasma fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment, the plasma fibrinogen level was found to be a possible biomarker for postoperative recurrence in advanced esophageal cancer patients who received neoadjuvant treatment. Moreover, plasma fibrinogen classification could be a simple and valuable predictive marker for postoperative follow up.

The impact of plasma fibrinogen levels on patients with vulvar cancer

To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters. In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients' survival. Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p=0.001), lymph node involvement (pN0 vs. pN1, p=0.04), and histological grade (G1 vs. G2 vs. G3, p=0.03), but not with patients' age (≤ 70 years vs. >70 years, p=0.6). In a multivariate survival analysis, tumor stage (p=0.006/p=0.02) and lymph node involvement (p<0.001/p<0.001), but neither histological grade (p=0.2/p=0.9) nor plasma fibrinogen levels (p=0.6/p=0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤ 70 years vs. >70 years) was associated with overall survival (p=0.03) but not with disease-free survival (p=0.1). Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer.

Plasma fibrinogen as a biomarker in gynecologic cancers.

Personalized MedicineVol. 8, No. 5 EditorialPlasma fibrinogen as a biomarker in gynecologic cancersClemens B TempferClemens B TempferDepartment of Obstetrics & Gynecology, Marienhospital Herne, Ruhr University Bochum, Bochum, Hölkeskampring 40, D-44625 Herne, Germany. Search for more papers by this authorEmail the corresponding author at clemens.tempfer@marienhospital-herne.dePublished Online:9 Sep 2011https://doi.org/10.2217/pme.11.47AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View article"Plasma fibrinogen as a biomarker in gynecologic cancers." , 8(5), pp. 501–502Keywords: cancercoagulationfibrinogenhypercoagulabilitymetastasispredictionprognosisBibliography1 Lawrence SO, Simpson-Haidaris PJ. Regulated de novo biosynthesis of fibrinogen in extrahepatic epithelial cells in response to inflammation. Thromb. Haemost.92,234–243 (2004).Crossref, Medline, CAS, Google Scholar2 Sahni A, Francis CW. Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. Blood96,3772–3778 (2000).Crossref, Medline, CAS, Google Scholar3 Sahni A, Khoranaa A, Baggs RB, Peng H, Francis CW. FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis. Blood107,126–131 (2006).Crossref, Medline, CAS, Google Scholar4 Simpson-Haidaris PJ, Rybarczyk B. Tumors and fibrinogen. The role of fibrinogen as an extracellular matrix protein. Ann. NY Acad. Sci.936,406–425 (2001).Crossref, Medline, CAS, Google Scholar5 Palumbo JS, Kombrinck KW, Drew AF et al. Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood96(10),3302–3309 (2000).Crossref, Medline, CAS, Google Scholar6 Palumbo JS, Potter JM, Kaplan LS, Talmage K, Jackson DG, Degen JL. Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res.62(23),6966–6972 (2002).Medline, CAS, Google Scholar7 Palumbo JS, Talmage KE, Massari JV et al. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood110(1),133–141 (2007).Crossref, Medline, CAS, Google Scholar8 Fibrinogen Studies Collaboration, Danesh J, Lewington S et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA294,1799–1809 (2005).Crossref, Medline, CAS, Google Scholar9 Woods A, Brull DJ, Humphries SE et al. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur. Heart J.21,1574–1583 (2000).Crossref, Medline, CAS, Google Scholar10 Takeuchi H, Ikeuchi S, Kitagawa Y et al. Pretreatment plasma fibrinogen level correlates with tumor progression and metastasis in patients with squamous cell carcinoma of the esophagus. J. Gastroenterol. Hepatol.22,2222–2227 (2007).Crossref, Medline, CAS, Google Scholar11 Yamashita H, Kitayama J, Kanno N et al. Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer6,147 (2006).Crossref, Medline, Google Scholar12 Wojtukiewicz MZ, Zacharski LR, Moritz TE et al. Prognostic significance of blood coagulation tests in carcinoma of the lung and colon. Blood Coagul. Fibrinolysis3,429–437 (1992).Crossref, Medline, CAS, Google Scholar13 Polterauer S, Grimm C, Seebacher V et al. Plasma fibrinogen levels and prognosis in patients with ovarian cancer: a multicenter study. Oncologist14(10),979–985 (2009).Crossref, Medline, Google Scholar14 Seebacher V, Polterauer S, Grimm C, Husslein H, Leipold H, Hefler-Frischmuth K. The prognostic value of plasma fibrinogen levels in patients with endometrial cancer: a multi-centre trial. Br. J. Cancer102(6),952–956 (2010).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByCurrent World LiteratureCurrent Opinion in Obstetrics & Gynecology, Vol. 25, No. 1 Vol. 8, No. 5 Follow us on social media for the latest updates Metrics Downloaded 114 times History Published online 9 September 2011 Published in print September 2011 Information© Future Medicine LtdKeywordscancercoagulationfibrinogenhypercoagulabilitymetastasispredictionprognosisFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

The prognostic value of plasma fibrinogen levels in patients with endometrial cancer: a multi-centre trial

Background:To analyse the correlation between pre-treatment plasma fibrinogen levels and clinical–pathological parameters in patients with endometrial cancer and to assess the value of plasma fibrinogen as a prognostic parameter.Methods:Within a retrospective multi-centre study, the records of 436 patients with endometrial cancer were reviewed and pre-treatment plasma fibrinogen levels were correlated with clinical–pathological parameters and patients’ survival.Results:The mean (s.d.) pre-treatment plasma fibrinogen level was 388.9 (102.4) mg per 100 ml. Higher plasma fibrinogen levels were associated with advanced tumour stage (FIGO I vs II vs III and IV, P=0.002), unfavourable histological subtype (endometrioid vs non-endometrioid histology, P=0.03), and higher patients’ age (⩽67 years vs >67 years, P=0.04), but not with higher histological grade (G1 vs G2 vs G3, P=0.2). In a multivariate analysis, tumour stage (P<0.001 and P<0.001), histological grade (P=0.009 and P=0.002), patients’ age (P=0.001 and P<0.001), and pre-treatment plasma fibrinogen levels (P=0.04 and P=0.02) were associated with disease-free and overall survival, respectively.Conclusion:Plasma fibrinogen levels can be used as an independent prognostic parameter for the disease-free and overall survival of patients with endometrial cancer.

Pretreatment plasma fibrinogen level correlates with tumor progression and metastasis in patients with squamous cell carcinoma of the esophagus

Hypercoagulation has been reported to be associated with tumor progression and a poor prognosis in various carcinomas. In this study, we examined fibrinogen levels in pretreated patients with esophageal squamous cell carcinoma (ESCC) and assessed its correlation with clinicopathological factors and prognosis in patients with ESCC. Pretreatment fibrinogen levels were examined prior to surgery or other treatments (e.g. endoscopic mucosal resection and chemoradiotherapy [CRT]) in 105 patients with primary ESCC. We investigated the association of fibrinogen levels with clinicopathological background factors and the survival of ESCC patients. The plasma fibrinogen concentration (PFC) ranged from 209.4 to 781.6 mg/dL. Pretreatment PFC correlated significantly with the depth of invasion (T factor). There also existed a significant correlation between higher fibrinogen levels and lymph node metastasis (N factor) and distant organ metastasis. Patients with a higher fibrinogen level experienced a significantly worse overall survival (P = 0.006). Fibrinogen levels strongly correlated with platelet counts, white blood cell counts and tumor length. Pretreatment PFC were observed to have a significant correlation with CRT responsiveness in ESCC patients in stages II and III (P = 0.005). This study revealed that higher levels of fibrinogen correlated with tumor progression, metastasis and poor responsiveness to CRT in ESCC patients.