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Harry J, Bucciol R, Finnigan D, Hashem H, Araki A, Othman M. The incidence of venous thromboembolism by type of solid cancer worldwide: A systematic review. Cancer Epidemiol 2025; 95:102764. [PMID: 39919489 DOI: 10.1016/j.canep.2025.102764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 12/21/2024] [Accepted: 02/02/2025] [Indexed: 02/09/2025]
Abstract
There is a well-established relationship between cancer and venous thromboembolism (VTE). Thrombosis in cancer is of major concern as it is a leading cause of mortality, impairs quality of life, and can adversely impact treatment protocols. Despite the role of thrombosis in cancer, no singular source consolidates data on VTE incidence by cancer type worldwide. This systematic review aims to report the incidence of VTE by type of solid cancer worldwide. The current analysis used three databases (MEDLINE, Embase, Cochrane Library) to identify relevant articles. All articles were written in English, assessed solid cancers in adults (≥18; males, females), and reported the incidence of VTE, or information that could be used to calculate incidence. After completing the search and removing duplicates, 3077 articles were assessed. All articles were screened by title and abstract, followed by a full-text review. A total of 124 articles were included in the final evaluation. The cumulative reported incidence of VTE across all types of solid cancer was 9.74 %. The highest reported incidence of VTE was in gastroesophageal cancer (15.43 %), whereas the lowest incidence was in prostate cancer (1.58 %). The two most reported cancers by country within our study cohort were colorectal (n = 23) and lung cancer (n = 23). The reported incidence of VTE in colorectal cancer was highest in Mexico (22.10 %), and lung cancer was highest in Canada (32.91 %). In conclusion, gathering data on global VTE rates in solid cancer identified high-risk cancers and highlighted under-investigated areas that require attention to reduce VTE occurrence in cancer patients.
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Affiliation(s)
- Jordan Harry
- School of Baccalaureate Nursing, St Lawrence College, Kingston, Canada
| | - Regan Bucciol
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada
| | - Deirdre Finnigan
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada
| | - Hussein Hashem
- School of Medicine, University of Galway, Galway, Ireland
| | - Ahmad Araki
- College of Medicine, Sulaiman Al Rajhi University, Saudi Arabia
| | - Maha Othman
- School of Baccalaureate Nursing, St Lawrence College, Kingston, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada; Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt.
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Pergialiotis V, Vogiatzi Vokotopoulou L, Vlachos DE, Liontos M, Kontomanolis E, Thomakos N. Pre-treatment thrombocytosis and ovarian cancer survival: A meta-analysis. Eur J Obstet Gynecol Reprod Biol X 2024; 22:100312. [PMID: 38745890 PMCID: PMC11091518 DOI: 10.1016/j.eurox.2024.100312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 03/16/2024] [Accepted: 04/27/2024] [Indexed: 05/16/2024] Open
Abstract
An association between thrombocytosis and cancer progression and decreased survival has been observed for various forms of cancer. The aim of this study was to evaluate the impact of pre-treatment thrombocytosis on ovarian cancer survival. Medline, Scopus, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar were searched systematically for studies that compared survival outcomes of patients with ovarian cancer who had pre-treatment thrombocytosis with survival outcomes of patients with normal platelet counts. Fourteen articles were retrieved, with a total of 5414 patients with ovarian cancer. The methodological quality of included studies ranged between moderate and high. Patients with advanced stage disease were more likely to have pre-treatment thrombocytosis, and this was associated with lower rates of optimal debulking. Thrombocytosis was also associated with increased likelihood of recurrence of ovarian cancer [hazard ratio (HR) 2.01, 95 % confidence interval (CI) 1.34-3.01] and increased risk of death from ovarian cancer (HR 2.29, 95 % CI 1.35-3.90). The incidence of deep vein thrombosis was comparable in both groups (odds ratio 1.62, 95 % CI 0.48-5.46). Considering these findings, it is evident that pre-treatment thrombocytosis in patients with ovarian cancer is associated with increased risk of recurrence and death. Pre-treatment thrombocytosis is a potential sign of advanced stage disease, and may be predictive of suboptimal tumour debulking during surgery. Its association with other factors that affect survival, including platinum resistance and response to targeted therapy, remains poorly explored, although preliminary data suggest a potential correlation.
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Affiliation(s)
- Vasilios Pergialiotis
- First Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, ‘Alexandra’ General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Lito Vogiatzi Vokotopoulou
- First Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, ‘Alexandra’ General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios-Efthymios Vlachos
- First Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, ‘Alexandra’ General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Michalis Liontos
- Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emmanuel Kontomanolis
- Department of Obstetrics and Gynaecology, Democritus University of Thrace, Alexandroupole, Greece
| | - Nikolaos Thomakos
- First Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, ‘Alexandra’ General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Kou J, Gao L, Ni L, Shao T, Ding J. Mechanism of Hirudin-Mediated Inhibition of Proliferation in Ovarian Cancer Cells. Mol Biotechnol 2024; 66:1062-1070. [PMID: 38184808 DOI: 10.1007/s12033-023-01003-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 11/22/2023] [Indexed: 01/08/2024]
Abstract
To investigate the inhibitory effect of hirudin on the cell proliferation of human ovarian cancer A2780 cells by preventing thrombin and its underlying molecular mechanism. Cell Counting Kit-8 (CCK-8) method was used to detect the effect of different concentrations of hirudin and thrombin on the cell proliferation of A2780 cells. PAR-1 wild-type overexpression plasmid was constructed utilizing enzyme digestion identification, and it was transferred to A2780 cells. Sequencing and Western blot were used to detect the changes in PAR-1 protein expression. Western blot detection of PKCα protein phosphorylation in A2780 cells was performed. We also implemented quantitative PCR to detect the mRNA expression levels of epithelial-mesenchymal transition (EMT)-related genes, CDH2, Snail, and Vimentin, in A2780 cells. 1 μg/ml hirudin treatment maximally inhibited the promotion of A2780 cell proliferation by thrombin. Hirudin inhibited the binding of thrombin to the N-terminus of PAR-1, hindered PKCα protein phosphorylation in A2780 cells, and downregulated the mRNA expression levels of CDH2, Snail, and Vimentin. In conclusion, hirudin inhibits the cell proliferation of ovarian cancer A2780 cells, and the underlying mechanism may be through downregulating the transcription level of EMT genes, CDH2, Snail, and Vimentin. This study indicates that hirudin may have a therapeutic potential as an anti-cancer agent for ovarian cancer.
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Affiliation(s)
- Junyan Kou
- Oncology Department of Integrated Traditional Chinese and Western Medicine, Hangzhou Cancer Hospital, No. 34 Yanguan Lane, Ziyang Street, Shangcheng District, Hangzhou, 310000, Zhejiang Province, China
| | - Liujie Gao
- Department of Oncology & Hematology, Hangzhou Red Cross Hospital, Hangzhou, 310003, Zhejiang Province, China
| | - Liwei Ni
- Oncology Department of Integrated Traditional Chinese and Western Medicine, Hangzhou Cancer Hospital, No. 34 Yanguan Lane, Ziyang Street, Shangcheng District, Hangzhou, 310000, Zhejiang Province, China
| | - Tingting Shao
- Oncology Department of Integrated Traditional Chinese and Western Medicine, Hangzhou Cancer Hospital, No. 34 Yanguan Lane, Ziyang Street, Shangcheng District, Hangzhou, 310000, Zhejiang Province, China
| | - Jiyuan Ding
- Department of Oncology & Hematology, Hangzhou Red Cross Hospital, Hangzhou, 310003, Zhejiang Province, China.
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Malte AL, Højbjerg JA, Larsen JB. Platelet Parameters as Biomarkers for Thrombosis Risk in Cancer: A Systematic Review and Meta-analysis. Semin Thromb Hemost 2024; 50:360-383. [PMID: 36921613 DOI: 10.1055/s-0043-1764381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in various settings while knowledge on platelet activation parameters is sparse. This report provides a systematic review and meta-analysis on available literature on associations between platelet count and/or function and arterial and venous thrombosis in adult cancer patients. The review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed and Embase were searched up to March 2022. The National Heart, Lung, and Blood Institute's tools were used for quality assessment. In total, 100 studies were included which investigated the association between CAT and platelet count (n = 90), platelet indices (n = 19), and platelet function/activation markers (n = 13) in patients with solid cancers (n = 61), hematological cancers (n = 17), or mixed cancer types (n = 22). Eighty-one studies had venous thrombosis as their outcome measure, while 4 had arterial thrombosis and 15 studies had both. We found significantly elevated odds ratio of 1.50 (95% confidence interval: 1.19-1.88) for thrombosis with higher platelet counts. We saw a tendency toward an association between markers of platelet activation in forms of mean platelet volume and soluble P selectin and both arterial and venous thrombosis. Only one study investigated dynamic platelet function using flow cytometry. In conclusion, platelet count is associated with CAT across different cancer types and settings. Platelet function or activation marker analysis may be valuable in assisting thrombosis risk assessment in cancer patients but is sparsely investigated so far.
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Affiliation(s)
- Anne Lind Malte
- Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Johanne Andersen Højbjerg
- Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Julie Brogaard Larsen
- Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Zhifei L, Yuexiang L, Shaofei C, Shuo L, Hongwei W, Chuntao G. Elevated preoperative plasma D-dimer level was an independent prognostic factor for patients with PDAC after curative resection: a retrospective analysis. Jpn J Clin Oncol 2023; 53:1058-1067. [PMID: 37539583 DOI: 10.1093/jjco/hyad090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/11/2023] [Indexed: 08/05/2023] Open
Abstract
OBJECTIVE In this study, the relationship between preoperative plasma D-dimer level and overall survival and recurrence free survival were evaluated in patients with curative resection of pancreatic ductal adenocarcinoma. METHODS Preoperative plasma D-dimer level of 573 patients with pancreatic ductal adenocarcinoma were collected. The univariate and multivariate Cox hazard models were used to identify independent variables associated with overall survival and recurrence free survival in this study. The Kaplan-Meier method was used to evaluate overall survival and recurrence free survival, and the differences between survival curves were analyzed using the Log-rank test. Continuous variables were presented as $\overline{x}\pm s$, parametric analysis was performed using t-test. Categorical variables were analyzed by means of the chi-square or Fisher's exact test. RESULTS Based on the analysis for the whole study, the results showed that patients in the elevated plasma D-dimer levels had a tendency to have an elder mean age (58.69 ± 8.32 years vs. 63.05 ± 8.44 years, P < 0.001), larger tumour size ≥4 cm (P = 0.006), advanced T stage (P = 0.024), N stage (P = 0.041), Tumor, Node and Metastasis (TNM) stage (P = 0.029) and postoperative complications (P = 0.042) was more likely occurred. Besides, according to the results of Cox multivariate analysis, elevated preoperative plasma D-dimer level was an independent prognostic factor not only for overall survival (Hazard Ratio (HR):1.430, 95% Confidence Interval (CI) (1.163-1.759), P = 0.001) but also for recurrence free survival (HR:1.236, 95% CI (1.018-1.500), P = 0.032). CONCLUSION In our study, the elevated preoperative plasma D-dimer level may act as an independent prognostic factor for overall survival and recurrence free survival in patients with pancreatic ductal adenocarcinoma after curative resection. Pancreatic ductal adenocarcinoma patients with elevated preoperative plasma D-dimer level had a worse prognosis than those with normal plasma D-dimer level; and the elevated preoperative plasma D-dimer level may imply heavy tumour burden and provide supplementary information regarding disease status.
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Affiliation(s)
- Li Zhifei
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Hexi District, Tianjin, China
- Department of Hepatobiliary-Pancreatic-Splenic Surgery, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China
| | - Liang Yuexiang
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Hexi District, Tianjin, China
| | - Chang Shaofei
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Hexi District, Tianjin, China
| | - Li Shuo
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Hexi District, Tianjin, China
| | - Wang Hongwei
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Hexi District, Tianjin, China
| | - Gao Chuntao
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Hexi District, Tianjin, China
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Tietie LE, Okunade KS, SoibI-Harry AP, John-Olabode SO, Anorlu RI. Potential clinical utility of plasma D-dimer levels among women with cervical cancer in Lagos, Nigeria. Ecancermedicalscience 2023; 17:1501. [PMID: 36816787 PMCID: PMC9937069 DOI: 10.3332/ecancer.2023.1501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Indexed: 02/01/2023] Open
Abstract
The link between plasma D-dimer levels and underlying malignancy has been established. How this translates in clinical practice as a marker of detection and prognosis of cervical cancer (CC) is still unknown. This study compared the plasma D-dimer levels in women with and without CC and assessed the associations between plasma D-dimer levels and the stage and grade of CC. It was a comparative cross-sectional study of 65 women with histological diagnosis of CC and an equal number of age-matched cancer-free women enrolled at the University Teaching Hospital in Lagos, Nigeria. Participants' sociodemographic and clinical data as well as venous blood samples for estimation of plasma D-dimer were collected for statistical analyses. A receiver operating characteristic (ROC) analysis is performed to select the cut-off value of plasma D-dimer for differentiating CC from non-cancer. There was a statistically significant difference in the median levels of plasma D-dimer of women with CC and their cancer-free comparison groups (3,120 (1,189-4,515) versus 210 (125-350) ng/mL; p = 0.001). A plasma D-dimer value of 543 ng/mL was chosen in a ROC analysis as the discriminatory cut-off to differentiate CC from non-cancer. There were significant associations between plasma D-dimer levels and the International Federation of Gynaecology and Obstetrics stage (p = 0.001) or grade (p = 0.001) of CC. The study, therefore, demonstrated the potential clinical usefulness of plasma D-dimer as a diagnostic and prognostic marker of CC.
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Affiliation(s)
- Lucky E Tietie
- Oncology and Pathological Studies Unit, Lagos University Teaching Hospital, Lagos 102215, Nigeria
| | - Kehinde S Okunade
- Oncology and Pathological Studies Unit, Lagos University Teaching Hospital, Lagos 102215, Nigeria,Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, PMB 12003, Lagos, Nigeria
| | - Adaiah P SoibI-Harry
- Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, PMB 12003, Lagos, Nigeria
| | - Sarah O John-Olabode
- Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, PMB 12003, Lagos, Nigeria
| | - Rose I Anorlu
- Oncology and Pathological Studies Unit, Lagos University Teaching Hospital, Lagos 102215, Nigeria,Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, PMB 12003, Lagos, Nigeria
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7
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Deng RX, Zhu XL, Zhang AB, He Y, Fu HX, Wang FR, Mo XD, Wang Y, Zhao XY, Zhang YY, Han W, Chen H, Chen Y, Yan CH, Wang JZ, Han TT, Chen YH, Chang YJ, Xu LP, Huang XJ, Zhang XH. Machine learning algorithm as a prognostic tool for venous thromboembolism in allogeneic transplant patients. Transplant Cell Ther 2023; 29:57.e1-57.e10. [PMID: 36272528 DOI: 10.1016/j.jtct.2022.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 11/15/2022]
Abstract
As a serious complication after allogenic hematopoietic stem cell transplantation (allo-HSCT), venous thromboembolism (VTE) is significantly related to increased nonrelapse mortality. Therefore distinguishing patients at high risk of death who should receive specific therapeutic management is key to improving survival. This study aimed to establish a machine learning-based prognostic model for the identification of post-transplantation VTE patients who have a high risk of death. We retrospectively evaluated 256 consecutive VTE patients who underwent allo-HSCT at our center between 2008 and 2019. These patients were further randomly divided into (1) a derivation (80%) cohort of 205 patients and (2) a test (20%) cohort of 51 patients. The least absolute shrinkage and selection operator (LASSO) approach was used to choose the potential predictors from the primary dataset. Eight machine learning classifiers were used to produce 8 candidate models. A 10-fold cross-validation procedure was used to internally evaluate the models and to select the best-performing model for external assessment using the test cohort. In total, 256 of 7238 patients were diagnosed with VTE after transplantation. Among them, 118 patients (46.1%) had catheter-related venous thrombosis, 107 (41.8%) had isolated deep-vein thrombosis (DVT), 20 (7.8%) had isolated pulmonary embolism (PE), and 11 (4.3%) had concomitant DVT and PE. The 2-year overall survival (OS) rate of patients with VTE was 68.8%. Using LASSO regression, 8 potential features were selected from the 54 candidate variables. The best-performing algorithm based on the 10-fold cross-validation runs was a logistic regression classifier. Therefore a prognostic model named BRIDGE was then established to predict the 2-year OS rate. The areas under the curves of the BRIDGE model were 0.883, 0.871, and 0.858 for the training, validation, and test cohorts, respectively. The Hosmer-Lemeshow goodness-of-fit test showed a high agreement between the predicted and observed outcomes. Decision curve analysis indicated that VTE patients could benefit from the clinical application of the prognostic model. A BRIDGE risk score calculator for predicting the study result is available online (47.94.162.105:8080/bridge/). We established the BRIDGE model to precisely predict the risk for all-cause death in VTE patients after allo-HSCT. Identifying VTE patients who have a high risk of death can help physicians treat these patients in advance, which will improve patient survival.
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Affiliation(s)
- Rui-Xin Deng
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiao-Lu Zhu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Ao-Bei Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Yun He
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Hai-Xia Fu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Feng-Rong Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiao-Dong Mo
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiang-Yu Zhao
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Yuan-Yuan Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Wei Han
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Huan Chen
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Yao Chen
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Chen-Hua Yan
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Jing-Zhi Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Ting-Ting Han
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Yu-Hong Chen
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Ying-Jun Chang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Lan-Ping Xu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiao-Jun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiao-Hui Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China.
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8
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Moik F, Ay C. Hemostasis and cancer: Impact of haemostatic biomarkers for the prediction of clinical outcomes in patients with cancer. J Thromb Haemost 2022; 20:2733-2745. [PMID: 36106749 PMCID: PMC9827869 DOI: 10.1111/jth.15880] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 01/13/2023]
Abstract
Patients with cancer are characterized by a dysregulation of the hemostatic system and systemic hypercoagulability. Different components of the hemostatic system are involved in tumor-promoting mechanisms including primary tumor growth, cancer cell invasion, immune evasion, angiogenesis, and the metastatic process. Therefore, different degrees of systemic hemostatic activation in patients with cancer can reflect distinct underlying biological phenotypes of cancer and seem to correlate with cancer aggressiveness. Peripheral blood levels of hemostatic biomarkers, indicating the activation status of different parts of the hemostatic system including the coagulation cascade, fibrinolytic activity, platelet activation, or endothelial activation, can be used to reflect cancer-associated systemic hypercoagulability. Thereby, hemostatic biomarkers represent promising candidates to investigate as surrogate markers for underlying cancer activity and progression dynamics and therefore as biomarkers for the prediction of clinical outcomes in cancer patients. In the present review, we provide an up-to-date summary of available data on hemostatic biomarkers for prognostication of overall survival and prediction of therapy response in patients with cancer, including specific oncologic treatment settings for potential clinical application. We provide a thorough discussion on potential clinical implementation and current limitations and highlight the most promising emerging biomarkers that might be used to contribute to risk-stratified, personalized oncologic decision making in the future.
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Affiliation(s)
- Florian Moik
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of ViennaViennaAustria
- Clinical Division of Oncology, Department of Internal Medicine, Medical University of GrazGrazAustria
| | - Cihan Ay
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of ViennaViennaAustria
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9
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Peng F, Yuan H, Zhou YF, Wu SX, Long ZY, Peng YM. Diagnostic Value of Combined Detection via Protein Induced by Vitamin K Absence or Antagonist II, Alpha-Fetoprotein, and D-Dimer in Hepatitis B Virus-Related Hepatocellular Carcinoma. Int J Gen Med 2022; 15:5763-5773. [PMID: 35770053 PMCID: PMC9236167 DOI: 10.2147/ijgm.s362359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 06/15/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose We aimed to explore the clinical diagnostic value of combined detection via protein induced by vitamin K absence or antagonist II (PIVKA-II), alpha-fetoprotein (AFP), and D-dimer (D-D) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Materials and Methods We analyzed PIVKA-II, AFP, and D-D levels in 291 subjects comprising liver cirrhosis (LC) patients (n = 143) and HCC patients (n = 148). Receiver operating characteristic (ROC) curves were used to analyze and compare the clinical diagnostic value of the three biomarkers for HBV-related HCC alone and in combination. Results The levels of PIVKA-II, AFP, and D-D were positively correlated with tumor size in HCC patients. The levels of PIVKA-II and AFP in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients were higher than those in LC patients, while the levels of D-D were lower. The area under the curve for combined detection was greater than that for single-index detection in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients. Conclusion D-D may be a useful biomarker for the diagnosis of HBV-related HCC. The combined detection of PIVKA-II, AFP, and D-D had better diagnostic value for different types of HCC than the detection of individual biomarkers.
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Affiliation(s)
- Fang Peng
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Hao Yuan
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
- Correspondence: Hao Yuan, Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China, Tel +8613677366519, Email
| | - Yi-Feng Zhou
- Operating Room, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Si-Xian Wu
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Zhen-Yi Long
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Ya-Meng Peng
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
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10
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Tamura R, Yoshihara K, Enomoto T. Therapeutic Strategies Focused on Cancer-Associated Hypercoagulation for Ovarian Clear Cell Carcinoma. Cancers (Basel) 2022; 14:2125. [PMID: 35565252 PMCID: PMC9099459 DOI: 10.3390/cancers14092125] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 04/22/2022] [Accepted: 04/23/2022] [Indexed: 02/04/2023] Open
Abstract
Ovarian clear cell carcinoma (OCCC) is associated with chemotherapy resistance and poor prognosis, especially in advanced cases. Although comprehensive genomic analyses have clarified the significance of genomic alterations such as ARID1A and PIK3CA mutations in OCCC, therapeutic strategies based on genomic alterations have not been confirmed. On the other hand, OCCC is clinically characterized by a high incidence of thromboembolism. Moreover, OCCC specifically shows high expression of tissue factor and interleukin-6, which play a critical role in cancer-associated hypercoagulation and may be induced by OCCC-specific genetic alterations or the endometriosis-related tumor microenvironment. In this review, we focused on the association between cancer-associated hypercoagulation and molecular biology in OCCC. Moreover, we reviewed the effectiveness of candidate drugs targeting hypercoagulation, such as tissue factor- or interleukin-6-targeting drugs, anti-inflammatory drugs, anti-hypoxia signaling drugs, anticoagulants, and combined immunotherapy with these drugs for OCCC. This review is expected to contribute to novel basic research and clinical trials for the prevention, early detection, and treatment of OCCC focused on hypercoagulation.
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Affiliation(s)
| | - Kosuke Yoshihara
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; (R.T.); (T.E.)
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11
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Tamura R, Yoshihara K, Matsuo K, Yachida N, Miyoshi A, Takahashi K, Sugino K, Yamaguchi M, Mori Y, Suda K, Ishiguro T, Okuda S, Motoyama T, Nakaoka H, Kikuchi A, Ueda Y, Inoue I, Enomoto T. Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma. Gynecol Oncol 2021; 163:327-333. [PMID: 34452748 DOI: 10.1016/j.ygyno.2021.08.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/12/2021] [Accepted: 08/14/2021] [Indexed: 01/26/2023]
Abstract
BACKGROUND Although ovarian clear cell carcinoma (CCC) is associated with high incidence of thromboembolism, the clinicopathological and biological significance of hypercoagulable status in CCC remains unclear. MATERIALS AND METHODS We retrospectively analyzed pretreatment D-dimer levels, thromboembolic status, and clinical outcome of 125 CCCs in the discovery set and 143 CCCs in two other independent validation sets. Next, we performed RNA sequencing of 93 CCCs and compared coagulation-related gene profiles with 2492 pan-cancer data. We investigated differences in molecular characteristics of CCC subclasses based on coagulation status. RESULTS In the discovery dataset, D-dimer elevation above the normal range was significantly associated with shorter progression-free and overall survival, irrespective to thromboembolic status. Multivariate analysis identified D-dimer elevation and clinical stage as an independent prognostic factors. We confirmed the prognostic significance of D-dimer elevation in the validation sets. Tissue factor and IL6, which are considered key elements of cancer-induced hypercoagulation, were highly expressed in CCC than in other cancers regardless of D-dimer level. Higher activity of various oncogenic pathways was observed in CCC with compared to without D-dimer elevation. Moreover, hierarchical cluster analysis divided 57 CCCs with D-dimer elevation into immunologically hot and cold tumor subtypes. Hot tumors were characterized by enrichment of T-cell inflamed phenotype, inflammation, the epithelial-mesenchymal transition, and high serum levels of CRP, and cold tumors by enrichment of cell cycle and MYC pathways. CONCLUSIONS CCC represents hypercoagulable disease and elevate D-dimer is a prognostic factor for decreased survival in CCC. D-dimer high CCC has distinct molecular characteristics into the inflammatory-driven pathway (hot tumor) and the immune-suppressive pathway (cold tumor). Treatment implication of our proposed molecular classification merits further investigation.
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Affiliation(s)
- Ryo Tamura
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Kosuke Yoshihara
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Koji Matsuo
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Nozomi Yachida
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Ai Miyoshi
- Department of Obstetrics and Gynecology, Osaka University School of Medicine, Suita, Japan
| | - Kotaro Takahashi
- Department of Gynecology, Niigata Cancer Center Hospital, Niigata, Japan
| | - Kentaro Sugino
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Manako Yamaguchi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yutaro Mori
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Kazuaki Suda
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tatsuya Ishiguro
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Shujiro Okuda
- Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Japan; Medical AI Center, Niigata University School of Medicine, Niigata, Japan
| | - Teiichi Motoyama
- Department of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hirofumi Nakaoka
- Department of Cancer Genome Research, Sasaki Institute, Tokyo, Japan
| | - Akira Kikuchi
- Department of Gynecology, Niigata Cancer Center Hospital, Niigata, Japan
| | - Yutaka Ueda
- Department of Obstetrics and Gynecology, Osaka University School of Medicine, Suita, Japan
| | - Ituro Inoue
- Human Genetics Laboratory, National Institute of Genetics, Mishima, Japan
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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12
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Falanga A, Marchetti M, Russo L. Hemostatic Biomarkers and Cancer Prognosis: Where Do We Stand? Semin Thromb Hemost 2021; 47:962-971. [PMID: 34450680 DOI: 10.1055/s-0041-1733925] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cancer patients are characterized by hypercoagulable state and an increased rate of thrombotic events, the most common being venous thromboembolism. Several hemostatic pathways that are significantly implicated in mechanisms of thromboembolic disease are also involved in growth, invasion, and metastatic spread of malignant cells as well in tumor-induced neo-angiogenesis. This close connection between cancer and the hemostatic system has prompted numerous studies on the role of alterations in the level plasma biomarkers of the different compartments of hemostasis in predicting cancer prognosis. In this review, we collect the results of several exemplificative studies that have evaluated clotting activation biomarkers in relation to different cancer outcomes with a final emphasis on current research and forthcoming directions in this field.
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Affiliation(s)
- Anna Falanga
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.,Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy
| | - Marina Marchetti
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Laura Russo
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
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13
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Ke X, Jin B, You W, Chen Y, Xu H, Zhao H, Lu X, Sang X, Zhong S, Yang H, Mao Y, Du S. Comprehensive analysis of coagulation indices for predicting survival in patients with biliary tract cancer. BMC Cancer 2021; 21:953. [PMID: 34433454 PMCID: PMC8390227 DOI: 10.1186/s12885-021-08684-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 08/12/2021] [Indexed: 11/10/2022] Open
Abstract
Background Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC. Methods The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram. Results Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging. Conclusions The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08684-w.
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Affiliation(s)
- Xindi Ke
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.,Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences & PUMC, Beijing, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Wen You
- Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences & PUMC, Beijing, China
| | - Yang Chen
- Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences & PUMC, Beijing, China
| | - Haifeng Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Shouxian Zhong
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.
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14
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Wang Y, Wang Y, Chen R, Tang Z, Peng Y, Jin Y, Lan A, Ding N, Dai Y, Jiang L, Liu S. Plasma fibrinogen acts as a predictive factor for pathological complete response to neoadjuvant chemotherapy in breast cancer: a retrospective study of 1004 Chinese breast cancer patients. BMC Cancer 2021; 21:542. [PMID: 33980202 PMCID: PMC8114717 DOI: 10.1186/s12885-021-08284-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 05/04/2021] [Indexed: 01/04/2023] Open
Abstract
Background The aim of this study was to evaluate the relationship between pre-treatment plasma fibrinogen (Fib) level and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and to assess the role of plasma Fib as a predictive factor. Methods Data from 1004 consecutive patients with invasive breast cancer who received NAC and subsequent surgery were retrospectively analysed. Both univariate and multivariate analyses based on logistic regression model were performed to identify clinicopathological factors associated with pCR to NAC. Cox regression model was used to determine the correlation between clinical or pathological parameters and recurrence-free survival (RFS). The Kaplan-Meier method and the log-rank test were applied in the survival analysis. Results The median value of Fib, rather than other plasma coagulation parameters, was significantly increased in non-pCR patients compared with pCR patients (P = 0.002). Based on the cut-off value estimated by the receiver operating characteristic (ROC) curve analysis, patients were divided into low or high Fib groups (Fib < 3.435 g/L or ≥ 3.435 g/L). Low Fib levels were significantly associated with premenopausal or perimenopausal status (P < 0.001), tumour size ≤5 cm (P = 0.002), and positive hormone receptor status (P = 0.002). After adjusted for other clinicopathological factors in the multivariate logistic regression model, low Fib status was strongly associated with pCR to NAC (OR = 3.038, 95% CI 1.667–5.537, P < 0.001). Survival analysis showed that patients with low Fib levels exhibited better 3-year RFS compared with patients with high Fib levels in the tumour size>5 cm group (77.5% vs 58.4%, log-rank, P = 0.0168). Conclusions This study demonstrates that low pre-treatment plasma Fib (Fib < 3.435 g/L) is an independent predictive factor for pCR to NAC in breast cancer patients. Moreover, T3-featured breast cancer patients with lower Fib level exhibit better RFS outcomes after NAC compared with high Fib status. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08284-8.
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Affiliation(s)
- Yihua Wang
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yu Wang
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Rui Chen
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China.,Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou Province, China
| | - Zhenrong Tang
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yang Peng
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yudi Jin
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Ailin Lan
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Nan Ding
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yuran Dai
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Linshan Jiang
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Shengchun Liu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
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15
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Liang YJ, Mei XY, Zeng B, Zhang SE, Yang L, Lao XM, Liao GQ. Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma. BMC Cancer 2021; 21:122. [PMID: 33546637 PMCID: PMC7863521 DOI: 10.1186/s12885-021-07841-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 01/26/2021] [Indexed: 12/20/2022] Open
Abstract
Background The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC. Methods We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed. Results Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC (P = 0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR = 2.1, P = 0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery (P = 0.005, 0.001 and 0.244, respectively). Conclusion In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-07841-5.
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Affiliation(s)
- Yu-Jie Liang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Xue-Ying Mei
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Bin Zeng
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Si-En Zhang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Le Yang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Xiao-Mei Lao
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China. .,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China.
| | - Gui-Qing Liao
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
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16
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Fang L, Xu Q, Qian J, Zhou JY. Aberrant Factors of Fibrinolysis and Coagulation in Pancreatic Cancer. Onco Targets Ther 2021; 14:53-65. [PMID: 33442266 PMCID: PMC7797325 DOI: 10.2147/ott.s281251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/11/2020] [Indexed: 12/13/2022] Open
Abstract
Aberrant factors associated with fibrinolysis and thrombosis are found in many cancer patients, which can promote metastasis and are associated with poor prognosis. The relationship between tumor-associated fibrinolysis and thrombosis is poorly understood in pancreatic cancer. This review provides a brief highlight of existing studies that the fibrinolysis and coagulation systems were activated in pancreatic cancer patients, along with aberrant high concentrations of tissue plasminogen activator (t-PA), urine plasminogen activator (u-PA), D-dimer, fibrinogen, or platelets. These factors cooperate with each other, propelling tumor cell shedding, localization, adhesion to distant metastasis. The relationship between thrombosis or fibrinolysis and cancer immune escape is also investigated. In addition, the potential prevention and therapy strategies of pancreatic cancer targeting factors in fibrinolysis and coagulation systems are also been discussed, in which we highlight two effective agents aspirin and low-molecular weight heparin (LMWH). Summarily, this review provides new directions for the research and treatment of pancreatic cancer.
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Affiliation(s)
- Lianghua Fang
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
| | - Qing Xu
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210029, People's Republic of China
| | - Jun Qian
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
| | - Jin-Yong Zhou
- Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
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17
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Guo Y, Jiang T, Ouyang L, Li X, He W, Zhang Z, Shen H, You Z, Yang G, Lai H. A novel diagnostic nomogram based on serological and ultrasound findings for preoperative prediction of malignancy in patients with ovarian masses. Gynecol Oncol 2020; 160:704-712. [PMID: 33357959 DOI: 10.1016/j.ygyno.2020.12.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/06/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVE To develop a novel diagnostic nomogram model to predict malignancy in patients with ovarian masses. METHODS In total, 1277 patients with ovarian masses were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was performed to identify valuable predictive factors. Univariate and multivariate logistic regression analyses were used to identify risk factors for ovarian cancer. Subsequently, a predictive nomogram model was developed. The performance of the nomogram model was assessed by its calibration and discrimination in a validation cohort. Decision curve analysis (DCA) was applied to assess the clinical net benefit of the model. RESULTS Overall, 496 patients (38.8%) had ovarian cancer. Eighteen parameters were significantly different between the malignant and benign groups. Five parameters were identified as being most optimal for predicting malignancy, including age, carbohydrate antigen 125, fibrinogen-to-albumin ratio, monocyte-to-lymphocyte ratio, and ultrasound result. These parameters were incorporated to establish a nomogram model, and this model exhibited an area under the ROC curve (AUC) of 0.937 (95% confidence interval [CI], 0.920-0.954). The model was also well calibrated in the validation cohort and showed an AUC of 0.925 (95%CI, 0.896-0.953) at the cut-off point of 0.298. DCA confirmed that the nomogram model achieved the best clinical utility with almost the entire range of threshold probabilities. The model has demonstrated superior efficacy in predicting malignancy compared to currently available models, including the risk of ovarian malignancy algorithm, copenhagen index, and the risk of malignancy index. More importantly, the nomogram established here showed potential value in identification of early-stage ovarian cancer. CONCLUSION The cost-effective and easily accessible nomogram model exhibited favorable accuracy for preoperative prediction of malignancy in patients with ovarian masses, even at early stages.
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Affiliation(s)
- Yunyun Guo
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Tengjia Jiang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, PR China
| | - Linglong Ouyang
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Xiaohui Li
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Weipeng He
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Zuwei Zhang
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Hongwei Shen
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Zeshan You
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China
| | - Guofen Yang
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China.
| | - Huiling Lai
- Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510060, Guangdong, PR China.
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18
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Li H, Wang H, Shao S, Gu Y, Yao J, Huang J. Pretreatment Albumin-to-Fibrinogen Ratio Independently Predicts Chemotherapy Response and Prognosis in Patients with Locally Advanced Rectal Cancer Undergoing Total Mesorectal Excision After Neoadjuvant Chemoradiotherapy. Onco Targets Ther 2020; 13:13121-13130. [PMID: 33380802 PMCID: PMC7767700 DOI: 10.2147/ott.s288265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 12/11/2020] [Indexed: 12/13/2022] Open
Abstract
Background Neoadjuvant chemoradiotherapy (nCRT) followed by surgery of total mesorectal excision (TME) is currently accepted as the standard treatment for locally advanced rectal cancer (LARC). This study aimed to investigate the potential prognostic factors, including the albumin-to-fibrinogen ratio (AFR) for LARC patients. Methods We retrospectively recruited LARC patients (cT3-4 and/or cN1-2) who underwent nCRT followed by TME between January 2011 and January 2015. The cut-off value of pretreatment AFR for overall survival (OS) was determined by the receiver operating characteristic (ROC) curve. The potential predictive factors for prognosis in the LARC patients were assessed by the univariate and multivariate Cox’s proportional hazard regression and Kaplan–Meier curve analyses. Results AFR was a significant predictor for OS with a cut-off value of 8.65 and an AUC of 0.882 (P<0.001). The pretreatment AFR level was the only independent risk factor for pathologic response to nCRT (HR: 2.44, 95% CI: 1.43–4.17, P=0.003), 5-year OS (HR: 3.31, 95% CI: 1.51–6.77, P=0.005) and disease-free survival (DFS) (HR: 2.73, 95% CI: 1.34–5.47, P=0.007) in LARC patients. A low pretreatment AFR level was significantly associated with a poor 5-year OS and DFS by the Log rank test (P=0.003 and 0.006, respectively). Conclusion Pretreatment AFR level was an independent prognostic factor in LARC patients undergoing TME after nCRT.
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Affiliation(s)
- Hongzhi Li
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China
| | - Honggang Wang
- Department of General Surgery, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China
| | - Shanshan Shao
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China
| | - Yawen Gu
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China
| | - Juan Yao
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China
| | - Junxing Huang
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China
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19
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Hufnagel DH, Cozzi GD, Crispens MA, Beeghly-Fadiel A. Platelets, Thrombocytosis, and Ovarian Cancer Prognosis: Surveying the Landscape of the Literature. Int J Mol Sci 2020; 21:ijms21218169. [PMID: 33142915 PMCID: PMC7663176 DOI: 10.3390/ijms21218169] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 10/26/2020] [Accepted: 10/27/2020] [Indexed: 12/16/2022] Open
Abstract
Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from in vitro, in vivo, and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease.
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Affiliation(s)
- Demetra H. Hufnagel
- Vanderbilt University School of Medicine, 2209 Garland Avenue, Nashville, TN 37240, USA; (D.H.H.); (G.D.C.)
| | - Gabriella D. Cozzi
- Vanderbilt University School of Medicine, 2209 Garland Avenue, Nashville, TN 37240, USA; (D.H.H.); (G.D.C.)
| | - Marta A. Crispens
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA;
- Vanderbilt-Ingram Cancer Center, 1301 Medical Center Drive, Nashville, TN 37232, USA
| | - Alicia Beeghly-Fadiel
- Vanderbilt-Ingram Cancer Center, 1301 Medical Center Drive, Nashville, TN 37232, USA
- Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, 2525 West End Avenue, Nashville, TN 37203, USA
- Correspondence:
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20
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Okunade KS, Dawodu O, Adenekan M, Nwogu CM, Awofeso O, Ugwu AO, Salako O, John-Olabode S, Olowoselu OF, Anorlu RI. Prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer. Niger J Clin Pract 2020; 23:1141-1147. [PMID: 32788493 PMCID: PMC8104071 DOI: 10.4103/njcp.njcp_134_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Aims This study was aimed at investigating the prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer (EOC) patients in Lagos, Nigeria. Methods This was a retrospective cohort study involving the review of the clinical record of 72 patients with histologically confirmed EOC who were managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. Information on the sociodemographic data and platelet counts at diagnosis of EOC were retrieved from the patients' medical records. Descriptive statistics were then computed for all baseline patients' characteristics. Survival analyses were carried out using the Kaplan-Meier estimates. Multivariate analysis of these data was performed with the Cox proportional hazards model. Results This study revealed that the prevalence of pretreatment thrombocytosis was 41.7% among the women with EOC. Fifty-three (73.6%) of the women had the advanced-stage disease (FIGO stage III-IV) while 52 (72.2%) had high-grade disease (II-III). The majority (66.7%) of the women had a serous histological type of EOC while 76.4% had documented recurrence. Pretreatment thrombocytosis was significantly associated with the women's parity (P = 0.009), serum carbohydrate antigen 125 levels (P = 0.018), median progression-free survival (PFS) (P < 0.001), 3-year median overall survival (OS) (P < 0.001), type of primary treatment (P = 0.002), extent of cytoreduction (P < 0.001), presence of ascites (P = 0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008), and histological type (P = 0.011). Pretreatment thrombocytosis was negatively associated with PFS (hazard ratio [HR] = 0.25; 95% CI 0.83, 0.75; P = 0.014) and 3-year OS (HR = 0.03; 95% CI 0.03, 0.27; P = 0.002). Conclusions The study suggests that pretreatment thrombocytosis may be a useful predictor of survivals in EOC patients.
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Affiliation(s)
- K S Okunade
- Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos; Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - O Dawodu
- Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - M Adenekan
- Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - C M Nwogu
- Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - O Awofeso
- Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - A O Ugwu
- Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - O Salako
- Department of Radiotherapy and Radiation Oncology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - S John-Olabode
- Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria
| | - O F Olowoselu
- Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria
| | - R I Anorlu
- Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos; Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
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21
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Li Z, Zhang G, Zhang M, Mei J, Weng H, Peng Z. Development and Validation of a Risk Score for Prediction of Venous Thromboembolism in Patients With Lung Cancer. Clin Appl Thromb Hemost 2020; 26:1076029620910793. [PMID: 32162530 PMCID: PMC7288811 DOI: 10.1177/1076029620910793] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A total of 827 patients with lung cancer from February 2013 to February 2018 in our hospital were retrospectively analyzed. Demographic and clinicopathological variables independently correlated to VTE were applied to develop the risk score in the development group while examined in the validation group. The regression coefficients of multivariable logistic regression test were applied to assign a risk score system. The incidence of VTE was 12.3%, 12.7%, and 11.8% in all patients, in the development and validation groups, respectively. The 496 patients in the development group were classified into 3 groups: low risk (scores ≤3), moderate risk (scores 4-5), and high risk (scores ≥6). The risk of VTE was significantly and positively related to the risk scores in both development and validation groups. The risk score system aided proper stratification of patients with either high or low risk of VTE in the development and validation groups (c statistic = 0.819 and 0.827, respectively). This risk score system based on the factors with most significant correlation showed good predictive ability and is potentially useful for predicting VTE in patients with lung cancer. However, it was developed and validated by a retrospective analysis and has significant limitations, and a prospective validation with all the classic variables assessing the thrombotic risk is needed for a solid conclusion.
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Affiliation(s)
- Zilun Li
- Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guolong Zhang
- Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mengping Zhang
- Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Mei
- Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huiwen Weng
- Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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22
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Marchetti M, Giaccherini C, Masci G, Verzeroli C, Russo L, Celio L, Sarmiento R, Gamba S, Tartari CJ, Diani E, Vignoli A, Malighetti P, Spinelli D, Kuderer NM, Nichetti F, Minelli M, Tondini C, Barni S, Giuliani F, Petrelli F, D'Alessio A, Gasparini G, Labianca R, Santoro A, De Braud F, Falanga A. Thrombin generation predicts early recurrence in breast cancer patients. J Thromb Haemost 2020; 18:2220-2231. [PMID: 32397009 DOI: 10.1111/jth.14891] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 04/28/2020] [Accepted: 04/30/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Cancer patients present with a hypercoagulable state often associated with poor disease prognosis. OBJECTIVES This study aims to evaluate whether thrombin generation (TG), a global coagulation test, may be a useful tool to improve the identification of patients at high risk of early disease recurrence (ie, E-DR within 2 years) after breast cancer surgery. PATIENTS/METHODS A cohort of 522 newly diagnosed patients with surgically resected high-risk breast cancer were enrolled in the ongoing prospective HYPERCAN study. TG potential was measured in plasma samples collected before starting systemic chemotherapy. Significant predictive hemostatic and clinic-pathological parameters were identified in the derivation cohort by Cox regression analysis. A risk prognostic score for E-DR was generated in the derivation and tested in the validation cohort. RESULTS After a median observation period of 3.4 years, DR occurred in 51 patients, 28 of whom were E-DR. E-DR subjects presented with the highest TG values as compared to both late-DR (from 2 to 5 years) and no relapse subjects (P < .01). Multivariate analysis in the derivation cohort identified TG, mastectomy, triple negative and Luminal B HER2-neg molecular subtypes as significant independent predictors for E-DR, which were utilized to generate a risk assessment score. In the derivation and validation cohorts, E-DR rates were 2.3% and 0% in the low-risk, 10.1% and 6.3% in the intermediate-risk, and 18.2% and 16.7%, in the high-risk categories, respectively. CONCLUSIONS Inclusion of TG in a risk-assessment model for E-DR significantly helps the identification of operated breast cancer patients at high risk of very early relapse.
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Affiliation(s)
- Marina Marchetti
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Cinzia Giaccherini
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Giovanna Masci
- Oncology Unit, IRCCS Humanitas Institute, Rozzano, Italy
| | - Cristina Verzeroli
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Laura Russo
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Luigi Celio
- Oncology Unit, IRCCS National Cancer Institute, Milan, Italy
| | | | - Sara Gamba
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Carmen J Tartari
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Erika Diani
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Alfonso Vignoli
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Paolo Malighetti
- Department of Management, Information and Production Engineering, University of Bergamo, Bergamo, Italy
| | - Daniele Spinelli
- Department of Management, Information and Production Engineering, University of Bergamo, Bergamo, Italy
| | | | | | - Mauro Minelli
- Oncology Unit, Hospital San Giovanni Addolorata, Rome, Italy
| | - Carlo Tondini
- Oncology Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Sandro Barni
- Oncology Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | | | - Fausto Petrelli
- Oncology Unit, Hospital Treviglio-Caravaggio, Treviglio, Italy
| | - Andrea D'Alessio
- Medical Oncology and Internal Medicine, Policlinico San Marco, Bergamo, Italy
| | | | - Roberto Labianca
- Department Oncology Bergamo Province, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | | | | | - Anna Falanga
- Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
- School of Medicine, University of Milan Bicocca, Italy
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23
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Hu Q, Hada A, Han L. Platelet count as a biomarker for monitoring treatment response and disease recurrence in recurrent epithelial ovarian cancer. J Ovarian Res 2020; 13:78. [PMID: 32682445 PMCID: PMC7368983 DOI: 10.1186/s13048-020-00682-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 07/07/2020] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES We sought to determine the impact of pretreatment plasma platelet levels, dimerized plasmin fragment (D-dimer) and fibrinogen in recurrent epithelial ovarian cancer (EOC) and the impact of platelet levels on SKOV3 cell lines growth and responsiveness to chemotherapy. METHODS Under approval of ethical committee, we identified 104 women with recurrent EOC who underwent treatment between January 2010 and February 2015. Reviewing clinical, laboratory, and pathologic records from this retrospective cohort, we analyzed the correlation between pretreatment plasma D-dimer, fibrinogen, platelet levels and clinicopathological parameters, progression free survival (PFS) and overall survival (OS). Inco-culture experiments human ovarian cancer SKOV3 cell lines were used to test the effect of platelet levels on tumor growth and responsiveness to docetaxel. RESULTS Of the 104 recurrent EOC, thrombocytosis at diagnosis and the decrease of platelet count by less than 25% after primary therapy were associated with worse median progression free survival (P = 0.003;P = 0.021) and median overall survival (P = 0.009;P = 0.009). Mean platelet levels declined at the end of primary therapy(P < 0.001) and rose at recurrence(P = 0.007). In multivariate analysis, elevated platelet levels at primary therapy and the decrease of platelet count less than 25% after primary therapy were unfavorable prognostic factor for PFS(P = 0.022; P = 0.015) and OS(P = 0.013;P = 0.007) in recurrent EOC, but elevated plasma D-dimer and fibrinogen were not. In SKOV-3 ovarian cancer cell lines, suitable concentration platelet co-culture protected against apoptosis (P < 0.05). CONCLUSIONS Platelet count during treatment could be used as a biomarker used for monitoring the disease recurrence and predicting treatment response. And platelet with suitable concentration co-culture protected against apoptosis in SKOV3 cell line, which may explain clinical observations.
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Affiliation(s)
- Qinghong Hu
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450002, People's Republic of China
| | - Abha Hada
- B.P. Koirala Institute of Health Sciences, Sunsari, Dharan, Nepal
| | - Liping Han
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, No.1, Jianshe East Road, Zhengzhou, Henan, 450002, P.R. China.
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24
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Cao X, Kong YL, Wang L, Zhu HY, Liang JH, Xia Y, Fan L, Shi WY, Liu H, Li JY, Xu W. High plasma D-dimer level is a poor prognostic factor for patients with waldenström macroglobulinemia. Leuk Lymphoma 2020; 61:1140-1146. [PMID: 31928271 DOI: 10.1080/10428194.2019.1709837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Waldenström Macroglobulinemia (WM) is a rare form of non-Hodgkin lymphoma with great heterogeneity, and data on the role of D-dimer in the progression of WM are limited. We retrospectively searched medical records for 110 newly diagnosed WM patients who were admitted to the department of hematology of the First Affiliated Hospital of Nanjing Medical University from January 2009 to December 2018. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Characteristics associated with elevated D-dimer level in WM patients were high serum beta-2 macroglobulin, elevated serum lactic dehydrogenase, cytogenetic abnormalities and late stage of the international stage system of WM. Patients with D-dimer >0.55 mg/L had worse OS and PFS. In conclusion, high level of D-dimer was associated with poor survival and acted as a negative predictor for untreated WM patients.
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Affiliation(s)
- Xin Cao
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Hematology, Affiliated Hospital of Nantong University, Nantong, China
| | - Yi-Lin Kong
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Li Wang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Hua-Yuan Zhu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Jin-Hua Liang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Yi Xia
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Lei Fan
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Wen-Yu Shi
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, China
| | - Hong Liu
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, China
| | - Jian-Yong Li
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Wei Xu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.,Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.,Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
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25
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Shiina Y, Nakajima T, Yamamoto T, Tanaka K, Sakairi Y, Wada H, Suzuki H, Yoshino I. The D-dimer level predicts the postoperative prognosis in patients with non-small cell lung cancer. PLoS One 2019; 14:e0222050. [PMID: 31877562 PMCID: PMC6932866 DOI: 10.1371/journal.pone.0222050] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 08/19/2019] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Carcinoma cells often modulate coagulation and fibrinolysis among cancer patients. Plasma dimerized plasmin fragment D (D-dimer) has been reported as a prognostic marker of various types of malignancies, including non-small cell lung cancer (NSCLC). However, the associations between the plasma D-dimer level and peripheral small NSCLC remain unclear. METHODS Three hundred and sixty-two patients with NSCLC who underwent radical surgery were retrospectively reviewed. Patients who received anticoagulation therapy before surgery or who lacked preoperative D-dimer data were excluded. The other 235 patients were divided into a high D-dimer (over 1.0 μg/mL) group (HDD group, n = 47) and a normal D-dimer group (NDD group, n = 188) and investigated for their clinical characteristics, computed tomography (CT) findings, pathological findings, and clinical outcomes. RESULTS The mean D-dimer levels was 2.49±2.58 μg/ml in the HDD group and 0.42±0.23 μg/ml in the NDD group. The HDD group was characterized by a predominance of male gender, older age, pure solid appearance on chest CT, vascular invasion in pathology, and a large solid part of the tumor. The HDD group showed a worse overall survival, disease-free survival, and disease-specific survival than the NDD group (p<0.001, <0.001, <0.001, respectively). These survival features were also observed in p-Stage IA disease. There was no marked survival difference when tumors showed ground-glass opacity on CT. CONCLUSION In NSCLC patients with a solid tumor appearance on CT, high D-dimer levels predict a poor survival and early recurrence.
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Affiliation(s)
- Yuki Shiina
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
| | - Takahiro Nakajima
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
- * E-mail:
| | - Takayoshi Yamamoto
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
| | - Kazuhisa Tanaka
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
| | - Yuichi Sakairi
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
| | - Hironobu Wada
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
| | - Hidemi Suzuki
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
| | - Ichiro Yoshino
- Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba Japan
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26
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Jin LJ, Chen WB, Zhang XY, Bai J, Zhao HC, Wang ZY. Analysis of factors potentially predicting prognosis of colorectal cancer. World J Gastrointest Oncol 2019; 11:1206-1217. [PMID: 31908725 PMCID: PMC6937433 DOI: 10.4251/wjgo.v11.i12.1206] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/05/2019] [Accepted: 08/26/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer. However, there is no systematic analysis of factors affecting the prognosis of colorectal cancer currently.
AIM To systematically analyze the influence of clinical data and serological and histological indicators on the prognosis of patients with colorectal cancer, and to explore the indicators that can accurately assess the prognosis of patients with colorectal cancer.
METHODS A total of 374 patients with colorectal cancer were enrolled. The clinical data, tumor-node-metastasis (TNM) stage, and Dukes stage were recorded. All patients received examinations including carcinoembryonic antigen (CEA), carbohydrate antigen 199, C-reactive protein, albumin, D-dimer, and fibrinogen as well as routine blood tests one week before surgery. The tumor location, size, depth of invasion, lymph node metastasis, and distant metastasis were recorded during surgery. The pathological tissue typing and expression of proliferating cell nuclear antigen (PCNA) and p53 were observed. All patients were followed for 3 years, and patients with endpoint events were defined as a poor prognosis group, and the remaining patients were defined as a good prognosis group. The differences in clinical data, serology, and histology were analyzed between the two groups. Multivariate COX regression was used to analyze the independent influencing factors for the prognosis of colorectal cancer. The receiver operating characteristic curve was used to evaluate the predictive value of each of the independent influencing factors and their combination for the prognosis of colorectal cancer.
RESULTS The follow-up outcomes showed that 81 patients were in the good prognosis group and 274 patients in the poor prognosis group. The TNM stage, PCNA, Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), D-dimer, and CEA were independent influencing factors for the prognosis of colorectal cancer (P = 0.000). NLR had the highest predictive power for colorectal cancer prognosis [area under the receiver operating characteristic curve (AUC) = 0.925], followed by D-dimer (AUC = 0.879) and GPS (AUC = 0.872). The accuracy of the combination of all indicators in predicting the prognosis of colorectal cancer was the highest (AUC = 0.973), which was significantly higher than that of any of the indicators alone (P < 0.05). The sensitivity and specificity of the combination were 92.59% and 90.51%, respectively.
CONCLUSION The independent influence factors for the prognosis of colorectal cancer include TNM stage, PCNA, GPS, NLR, CAR, D-dimer, and CEA. The combined assessment of the independent factors is the most accurate predictor of the prognosis after colorectal cancer surgery.
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Affiliation(s)
- Li-Jun Jin
- Department of Surgical Oncology (Division III), Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
| | - Wei-Bin Chen
- Department of Radiology, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei Province, China
| | - Xiao-Yu Zhang
- Department of Surgical Oncology (Division III), Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
| | - Jie Bai
- Department of Surgical Oncology (Division III), Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
| | - Hao-Chen Zhao
- Department of Anesthesiology (Division II), Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
| | - Zun-Yi Wang
- Department of Surgical Oncology (Division III), Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
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Yan M, Pan XT, Cheng X, Lu Y. Characteristics and significance of changes of thrombomodulin and plasma protein C in patients with cancer before and after PICC. Indian J Cancer 2019; 57:27-30. [PMID: 31736467 DOI: 10.4103/ijc.ijc_252_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Objective This study aimed to evaluate the changes and clinical significance of thrombomodulin (TM) and plasma protein C (PC) in patients with cancer before and after peripherally inserted central catheter placement (PICC). Materials and Methods The levels of plasma TM and PC in 35 patients with cancer before and after PICC were measured by enzyme-linked immunosorbent assay, and the significance of the differences was analyzed. Results TM was 3.57 ± 1.01 μg/L at 1 day after catheterization, which was significantly lower than the value of 4.41 ± 1.26 μg/L before catheterization; these values were 4.30 ± 1.81 and 4.73 ± 0.97 μg/L at 30 and 90 days after catheterization, respectively (F = 4.14,P < 0.05). PC was 3.32 ± 1.35 μg/L at 1 day after catheterization, which was significantly lower than the value of 5.32 ± 2.12 μg/L before catheterization; these values were 4.64 ± 2.44 and 5.83 ± 3.14 μg/L at 30 and 90 days after catheterization, respectively (F = 6.28,P < 0.01). There were no significant differences in platelet (PLT) counts, plasma D-D, and coagulation parameters among the four time points before and after catheterization. There was a positive correlation between TM and PC (r = 0.5420,P < 0.01) on day 1 after PICC line insertion. The levels of TM and PC were not related to PLT, plasma D-dimer, or various coagulation parameters. Conclusions The levels of TM and PC in the patients 1 day after PICC were significantly decreased and showed a positive correlation, but were not related to PLT, plasma D-dimer, or coagulation function.
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Affiliation(s)
- Min Yan
- Department of Hematology and Oncology, Taicang Hospital Affiliated to Suzhou University, Taicang, China
| | - Xiang-Tao Pan
- Department of Hematology and Oncology, Taicang Hospital Affiliated to Suzhou University, Taicang, China
| | - Xu Cheng
- Department of Hematology and Oncology, Taicang Hospital Affiliated to Suzhou University, Taicang, China
| | - Ye Lu
- Department of Hematology and Oncology, Taicang Hospital Affiliated to Suzhou University, Taicang, China
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Jin LJ, Chen WB, Zhang XY, Bai J, Zhao HC, Wang ZY. Analysis of factors potentially predicting prognosis of colorectal cancer. World J Gastrointest Oncol 2019. [DOI: 10.4251/wjgo.v11.i11.1206] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Fibrinogen and Albumin Score Changes during Preoperative Treatment Can Predict Prognosis in Patients with Locally Advanced Rectal Cancer. Gastroenterol Res Pract 2019; 2019:3514586. [PMID: 31814824 PMCID: PMC6877962 DOI: 10.1155/2019/3514586] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 10/21/2019] [Indexed: 12/24/2022] Open
Abstract
Background Fibrinogen (Fib) and albumin (Alb) levels are indicators of systemic inflammatory responses. Elevated Fib and decreased Alb levels are considered negative prognostic factors in different types of cancer. Here, we explored the prognostic value of changes in pre- and post- neoadjuvant chemoradiotherapy (NCRT) plasma fibrinogen and serum albumin (FA) scores in patients with locally advanced rectal cancer (LARC). Methods A total of 106 patients with LARC who underwent NCRT followed by surgical resection at Jinhua Municipal Central Hospital between 2011 and 2015 were analyzed. In addition, plasma Fib and serum Alb levels before and after NCRT were collected. FA scores were calculated based on the Fib and Alb levels dichotomized by clinical reference values. Patients were classified into two groups based on the changes in FA scores during NCRT: in group A, FA scores decreased or remained unchanged (n = 84), and in group B, FA scores increased (n = 22). Changes in FA scores were compared with patient outcomes. Results Increased FA scores were associated with worse disease-free survival (DFS) and overall survival (OS) in patients with LARC. The occurrence of systemic failure was higher in group B than in group A (40.9% vs. 19%, P = 0.032). In multivariate analysis, changes in FA scores, pretreatment carcinoembryonic antigen (CEA) levels, and pathologic differentiation were independent prognostic parameters for DFS and changes in FA scores and pretreatment CEA levels were independent prognostic parameters for OS. Conclusions Increased FA score after NCRT was an independent negative prognostic factor for DFS and OS in patients with NCRT-treated LARC.
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Differential Expression and Diagnostic Significance of Pre-Albumin, Fibrinogen Combined with D-Dimer in AFP-Negative Hepatocellular Carcinoma. Pathol Oncol Res 2019; 26:1669-1676. [PMID: 31578661 DOI: 10.1007/s12253-019-00752-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 09/12/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most malignant cancers with high morbidity and mortality. Nowadays, AFP-negative hepatocellular carcinoma (AFP-NHCC) has been found in many HCC patients and AFP analysis can't be used to screen HCC in these cases. In this study, we have examined the expression patterns of pre-albumin (PA), fibrinogen, D-Dimer and their clinical significance in AFP-NHCC. We recruited 214 AFP-NHCC patients and 210 controls in the study. PA, fibrinogen and D-Dimer levels were detected by turbidimetry, clauss and immunoturbidimetry methods, respectively. Serum PA levels were significantly lower in AFP-NHCC (84.5 ± 24.7 mg/L) than that in the controls (240.6 ± 59.4 mg/L, P < 0.05). For plasma fibrinogen levels, there was no difference between the controls (2.9 ± 0.7 g/L) and AFP-NHCC (2.5 ± 0.7 g/L). Compared with AFP-NHCC (0.8 ± 0.2 mg/L), plasma D-Dimer levels were significantly lower in controls (0.1 ± 0.0 mg/L, P < 0.05). The levels of PA, fibrinogen and D-Dimer were significantly correlated with differentiation (P < 0.01), and the PA and D-Dimer values were correlated with TNM stage (P < 0.05). Moreover, PA levels were correlated with tumor size (P = 0.034). Receiver operating characteristic curve (ROC) analyses elaborated that combination of PA, fibrinogen and D-Dimer possessed a higher sensitivity (93.4%) for differentiating AFP-NHCC from the controls, but the diagnostic specificity was reduced due to the combination of fibrinogen. After adjusting for all significant outcome predictors of the univariate logistic regression analysis, low levels of PA and high levels of D-Dimer were remained independent unfavorable outcome predictors (P < 0.05). Our data suggested that the expression levels of PA, fibrinogen and D-Dimer played critical roles in AFP-NHCC tumorigenesis. Moreover, PA and D-Dimer might be considered as potential diagnostic indicators in AFP-NHCC.
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Abstract
Metastatic cancers impose significant burdens on patients, affecting quality of life, morbidity, and mortality. Even during remission, microscopic metastases can lurk, but few therapies directly target tumor cell metastasis. Agents that interfere with this process would represent a new paradigm in cancer management, changing the 'waiting game' into a time of active prevention. These therapies could take multiple forms based on the pathways involved in the metastatic process. For example, a phenome-wide association study showed that a single nucleotide polymorphism in the gene TBXA2R is associated with increased metastasis in multiple primary cancers (P = 0.003), suggesting clinical applicability of TBXA2R antagonists. Emerging data related to the role of platelets in metastasis are concordant with our sense that these pathways present significant opportunities for therapeutic development. However, before real progress can be made toward clinical targeting of the metastatic process, foundational work is needed to define informative measures of critical elements such as circulating tumor cells and tumor DNA, and circulatory vs. lymphatic spread. These challenges require an expansion of team science and composition to obtain competitive funding. At our academic medical center, we have implemented a Cancer Metastasis Inhibition (CMI) program investigating this approach across multiple cancers.
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Stukan M, Badocha M, Ratajczak K. Development and validation of a model that includes two ultrasound parameters and the plasma D-dimer level for predicting malignancy in adnexal masses: an observational study. BMC Cancer 2019; 19:564. [PMID: 31185938 PMCID: PMC6558858 DOI: 10.1186/s12885-019-5629-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Accepted: 04/23/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Pre-operative discrimination of malignant from benign adnexal masses is crucial for planning additional imaging, preparation, surgery and postoperative care. This study aimed to define key ultrasound and clinical variables and develop a predictive model for calculating preoperative ovarian tumor malignancy risk in a gynecologic oncology referral center. We compared our model to a subjective ultrasound assessment (SUA) method and previously described models. METHODS This prospective, single-center observational study included consecutive patients. We collected systematic ultrasound and clinical data, including cancer antigen 125, D-dimer (DD) levels and platelet count. Histological examinations served as the reference standard. We performed univariate and multivariate regressions, and Bayesian information criterion (BIC) to assess the optimal model. Data were split into 2 subsets: training, for model development (190 observations) and testing, for model validation (n = 100). RESULTS Among 290 patients, 52% had malignant disease, including epithelial ovarian cancer (72.8%), metastatic disease (14.5%), borderline tumors (6.6%), and non-epithelial malignancies (4.6%). Significant variables were included into a multivariate analysis. The optimal model, included three independent factors: solid areas, the color score, and the DD level. Malignant and benign lesions had mean DD values of 2.837 and 0.354 μg/ml, respectively. We transformed established formulae into a web-based calculator ( http://gin-onc-calculators.com/gynonc.php ) for calculating the adnexal mass malignancy risk. The areas under the curve (AUCs) for models compared in the testing set were: our model (0.977), Simple Rules risk calculation (0.976), Assessment of Different NEoplasias in the adneXa (ADNEX) (0.972), Logistic Regression 2 (LR2) (0.969), Risk of Malignancy Index (RMI) 4 (0.932), SUA (0.930), and RMI3 (0.912). CONCLUSIONS Two simple ultrasound predictors and the DD level (also included in a mathematical model), when used by gynecologist oncologist, discriminated malignant from benign ovarian lesions as well or better than other more complex models and the SUA method. These parameters (and the model) may be clinically useful for planning adequate management in the cancer center. The model needs substantial validation.
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Affiliation(s)
- Maciej Stukan
- Department of Gynecologic Oncology, Gdynia Oncology Center, Pomeranian Hospitals, Gdynia, Poland, Postal address: ul. Powstania Styczniowego 1, 81-519 Gdynia, Poland
| | - Michał Badocha
- Department of Physical Chemistry, Gdańsk University of Technology, Gdańsk, Poland, Postal address: ul. Gabriela Narutowicza 11/12, 80-233 Gdańsk, Poland
| | - Karol Ratajczak
- Karol Ratajczak Consulting, ul. Damroki 1A, 80-175, Gdańsk, Poland
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Kawakami E, Tabata J, Yanaihara N, Ishikawa T, Koseki K, Iida Y, Saito M, Komazaki H, Shapiro JS, Goto C, Akiyama Y, Saito R, Saito M, Takano H, Yamada K, Okamoto A. Application of Artificial Intelligence for Preoperative Diagnostic and Prognostic Prediction in Epithelial Ovarian Cancer Based on Blood Biomarkers. Clin Cancer Res 2019; 25:3006-3015. [DOI: 10.1158/1078-0432.ccr-18-3378] [Citation(s) in RCA: 119] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 01/08/2019] [Accepted: 02/18/2019] [Indexed: 12/20/2022]
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Plasminogen Activator Inhibitor Type 1 in Blood at Onset of Chemotherapy Unfavorably Affects Survival in Primary Ovarian Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1153:47-54. [DOI: 10.1007/5584_2019_353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Song H, Kuang G, Zhang Z, Ma B, Jin J, Zhang Q. The Prognostic Value of Pretreatment Plasma Fibrinogen in Urological Cancers: A Systematic Review and Meta-analysis. J Cancer 2019; 10:479-487. [PMID: 30719143 PMCID: PMC6360290 DOI: 10.7150/jca.26989] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 10/21/2018] [Indexed: 12/30/2022] Open
Abstract
Objective: Growing evidence suggests pretreatment fibrinogen can serve as a prognostic marker in various malignancies. However, there are contradictory results about the prognostic role of fibrinogen in urological cancers. We conducted a meta-analysis to evaluate the association between pretreatment plasma fibrinogen and survival outcomes in urological cancers. Methods: After a systematic search of PubMed and Embase, we included 14 studies in our meta-analysis, and estimated hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS) using a fixed-effect model. Results: Our results indicate that pretreatment plasma fibrinogen is a prognostic factor in urological cancers (OS: HR=2.21, 95% CI=1.91-2.57, P<0.001, CSS: HR=2.67, 95% CI=2.23-3.19, P<0.001). Elevated pretreatment plasma fibrinogen is associated with poorer survival in prostate cancer (OS: HR=2.26, 95% CI=1.47-3.48, P<0.001; CSS: HR=2.42, 95% CI=1.44-4.07, P=0.001), renal cell carcinoma (OS: HR=2.13, 95% CI=1.75-2.61, P<0.001; CSS: HR=2.99, 95% CI=2.29-3.89, P<0.001) and upper tract urothelial carcinoma (OS: HR=2.34, 95% CI=1.81-3.02, P<0.001; CSS: HR=2.43, 95% CI=1.84-3.20, P<0.001). Subgroup analyses showed that plasma fibrinogen has a more negative impact on survival in Caucasian patients (OS: HR=2.52, 95% CI=1.95-3.25, P<0.001; CSS: HR=2.83, 95% CI=1.92-4.17, P<0.001) than Asian patients (OS: HR=2.07, 95% CI=1.73-2.49, P<0.001; CSS: HR=2.63, 95% CI=2.14-3.22, P<0.001). The prognostic value of fibrinogen is also consistent when stratified by different cut-off values. Conclusions: These results show that high pretreatment plasma fibrinogen levels can predict poorer OS and CSS in patients with urological cancers.
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Affiliation(s)
- Haifeng Song
- Department of Urology, Peking University First Hospital, Beijing 100034, China.,Institute of Urology, Peking University, Beijing 100034, China.,National Research Center for Genitourinary Oncology, Beijing 100034, China
| | - Guanyu Kuang
- Institute of Urology, Peking University, Beijing 100034, China.,National Research Center for Genitourinary Oncology, Beijing 100034, China
| | - Zhenan Zhang
- Department of Urology, Peking University First Hospital, Beijing 100034, China.,Institute of Urology, Peking University, Beijing 100034, China.,National Research Center for Genitourinary Oncology, Beijing 100034, China
| | - Binglei Ma
- Department of Urology, Peking University First Hospital, Beijing 100034, China.,Institute of Urology, Peking University, Beijing 100034, China.,National Research Center for Genitourinary Oncology, Beijing 100034, China
| | - Jie Jin
- Department of Urology, Peking University First Hospital, Beijing 100034, China.,Institute of Urology, Peking University, Beijing 100034, China.,National Research Center for Genitourinary Oncology, Beijing 100034, China
| | - Qian Zhang
- Department of Urology, Peking University First Hospital, Beijing 100034, China.,Institute of Urology, Peking University, Beijing 100034, China.,National Research Center for Genitourinary Oncology, Beijing 100034, China
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Falanga A, Marchetti M. Hemostatic biomarkers in cancer progression. Thromb Res 2018; 164 Suppl 1:S54-S61. [PMID: 29703485 DOI: 10.1016/j.thromres.2018.01.017] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 01/08/2018] [Accepted: 01/10/2018] [Indexed: 02/06/2023]
Abstract
Malignant disease is characterized by a hemostatic imbalance, usually shifted towards a procoagulant direction, and a high incidence of thrombotic complications. The mechanisms of hemostasis that are critically involved in thrombosis are also implicated in tumor progression, angiogenesis, and metastatic spread. As there is a close relationship between cancer and the clotting system, circulating biomarkers of activation of various hemostasis compartments (i.e. coagulation, fibrinolysis, platelets, endothelium, and other blood cells) have been extensively studied to predict cancer outcomes along with predicting the thrombotic risk. In this review, we will summarize the results of published studies and will focus on ongoing research and future directions of clotting activation bioproducts as biomarkers of cancer disease and progression.
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Affiliation(s)
- Anna Falanga
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| | - Marina Marchetti
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
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Malaguarnera M, Latteri S, Bertino G, Madeddu R, Catania VE, Currò G, Borzì AM, Drago F, Malaguarnera G. D-dimer plasmatic levels as a marker for diagnosis and prognosis of hepatocellular carcinoma patients with portal vein thrombosis. Clin Exp Gastroenterol 2018; 11:373-380. [PMID: 30323642 PMCID: PMC6174900 DOI: 10.2147/ceg.s172663] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose Portal vein thrombosis (PVT) is one of the severe complications of hepatocellular carcinoma (HCC). PVT deteriorates the liver, and its dysfunction increases the risk of bleeding, influencing the prognosis of patients with liver cirrhosis and HCC. The aim of our study was to investigate whether D-dimer testing could be a sensitive marker for the diagnosis and prognosis of HCC patients with PVT. Patients and methods Between June 2010 and December 2015, 118 HCC patients were admitted to Cannizzaro Hospital, Catania, and 50 controls were recruited from their relatives for health examinations. All enrolled patients were diagnosed and pathologically confirmed as having HCC. D-dimer was measured with an enzyme-linked immunosorbent assay using 2 monoclonal antibodies against nonoverlapping determinants of D-dimer. Results D-dimer levels in HCC patients with PVT were significantly higher vs HCC patients without PVT, P<0.002, and vs controls, P<0.001. Conclusion Plasma D-dimer is a sensitive marker of fibrin turnover and allows for the recognition of activated coagulation which may be manifested in HCC with PVT.
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Affiliation(s)
- Michele Malaguarnera
- Department of Biomedical and Biotechnological Science, University of Catania, Catania, Italy, .,Research Center "The Great Senescence", University of Catania, Catania, Italy
| | - Saverio Latteri
- Department of Medical, Surgical Sciences and Advanced Technologies "Gian Filippo Ingrassia", University of Catania, Catania, Italy
| | - Gaetano Bertino
- Department of Experimental and Clinical Medicine, University of Catania, Catania, Italy
| | - Roberto Madeddu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Vito Emanuele Catania
- Department of Medical, Surgical Sciences and Advanced Technologies "Gian Filippo Ingrassia", University of Catania, Catania, Italy
| | - Giuseppe Currò
- Department of Human Pathology, University of Messina, Messina, Italy
| | - Antonio Maria Borzì
- Research Center "The Great Senescence", University of Catania, Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Science, University of Catania, Catania, Italy,
| | - Giulia Malaguarnera
- Department of Biomedical and Biotechnological Science, University of Catania, Catania, Italy,
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Ye Q, Cheng J, Ye M, Liu D, Zhang Y. Association of pretreatment thrombocytosis with prognosis in ovarian cancer: a systematic review and meta-analysis. J Gynecol Oncol 2018; 30:e5. [PMID: 30479089 PMCID: PMC6304413 DOI: 10.3802/jgo.2019.30.e5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 08/20/2018] [Accepted: 09/05/2018] [Indexed: 01/30/2023] Open
Abstract
Objective To investigate the association between pre-treatment thrombocytosis and prognosis in patients with ovarian cancer (OC). Methods PubMed, EMBASE, and the Cochrane Library were searched for articles regarding the prognosis of OC patients with pre-treatment thrombocytosis by the end of March 2018. Pooled estimates for overall survival (OS) and progression-free survival (PFS) events were calculated as hazard ratios (HRs) either on a fixed or random effect model by Stata 13.0 software. Funnel plot and Egger's test were applied to evaluate publication bias and sensitivity analyses were undertaken to estimate the strength of outcomes. Results Eleven studies that met the inclusion criteria were enrolled, including a total of 4,953 patients. Pooled results showed that pre-treatment thrombocytosis was significantly associated with OS (HR=1.722; 95% confidence interval [CI]=1.437–2.064) and PFS (HR=1.452; 95% CI=1.323–1.593) in the cohort. Significant correlation was found in OS and PFS between pre-treatment thrombocytosis and both epithelial OC (all stages and differentiation degrees of OC) and advanced epithelial OC (III or IV) by subgroup analyses, which were performed according to publication year, country, case numbers, OC category, International Federation of Gynecology and Obstetrics stage, and cut-off value. However, subgroup analyses indicated no significant correlation between pre-treatment thrombocytosis and OS for patients with high-grade serous (poorly differentiated or undifferentiated) OC (HR=1.220; 95% CI=0.946–1.573; p=0.125). Egger's test demonstrated no obvious publication bias in the articles enrolled in this study (OS: p=0.226; PFS: p=0.071). Conclusion Pre-treatment thrombocytosis might be taken as an independent prognostic indicator for patients with OC.
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Affiliation(s)
- Qingjian Ye
- Department of Gynecology, the Third Affiliate Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Juan Cheng
- Department of Gynecology, the Third Affiliate Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Minjuan Ye
- Department of Gynecology, the Third Affiliate Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Dong Liu
- Department of Gynecology, the Third Affiliate Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yu Zhang
- Department of Gynecology, the Third Affiliate Hospital of Sun Yat-Sen University, Guangzhou, China.
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Serhan K, Gartung A, Panigrahy D. Drawing a link between the thromboxane A 2 pathway and the role of platelets and tumor cells in ovarian cancer. Prostaglandins Other Lipid Mediat 2018; 137:40-45. [PMID: 29933028 DOI: 10.1016/j.prostaglandins.2018.06.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 06/13/2018] [Accepted: 06/18/2018] [Indexed: 12/21/2022]
Abstract
Ovarian cancer is the most lethal gynecologic malignancy among women. Due to the heterogeneity and complexity of the disease, as well as the insidious onset of symptoms, timely diagnosis remains extremely challenging. Despite recent advances in chemotherapy regimens for ovarian cancer patients, many still suffer from recurrence and ultimately succumb to the disease; thus, there is an urgent need for the identification of novel therapeutic targets. Within this rapidly evolving field, the role of platelets in the ovarian cancer tumor microenvironment has garnered increased attention. It is well-established that platelets and tumor cells exhibit bidirectional communication in which platelets enhance tumor cell invasion, extravasation, and protection from host system defenses, while tumor cells serve as platelet agonists, increasing platelet adhesion, aggregation, and degranulation. This mini-review focuses on the platelet-tumor cell relationship in ovarian cancer, specifically highlighting the essential role of bioactive lipid mediators at this interface.
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Affiliation(s)
- Karolina Serhan
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
| | - Allison Gartung
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Dipak Panigrahy
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
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Li C, Jia L, Wang Z, Niu L, An X. Therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia and the risk factors for postoperative recurrence. Exp Ther Med 2018; 15:4431-4435. [PMID: 29725383 PMCID: PMC5920273 DOI: 10.3892/etm.2018.5986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 02/27/2018] [Indexed: 11/17/2022] Open
Abstract
The present study investigated the therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia (SVT), and explored the risk factors for postoperative recurrence. A total of 312 patients with pediatric SVT were selected in the Affiliated Children's Hospital of Xuzhou Medical University from April, 2011 to March, 2017. All the patients were subjected to radiofrequency ablation, and clinical data were retrospectively analyzed. Tilt table test was performed before and after treatment, and heart rate, systolic and diastolic blood pressure before and after treatment were compared. Plasma levels of D-dimer (D-D), platelet α-granule membrane protein (GMP-140) and thrombin-antithrombin III complex (TAT) were detected by enzyme-linked immunosorbent assay before treatment, immediately after radiofrequency oblation, and at 1, 3 and 7 days after treatment. Treatment outcomes were compared between the atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT) groups. Risk factors for postoperative recurrence were analyzed. Supine position heart rate after treatment was not significantly different from that before treatment (P>0.05), while the upright position heart rate was significantly increased after treatment (P<0.05). Systolic pressures of the supine and upright positions were significantly reduced after treatment compared with the levels before (P<0.05), but no significant differences were found in diastolic blood pressure of supine and the upright position (P>0.05). No significant difference in radiofrequency ablation rate, recurrence rate and incidence of complications were found between the AVRT and AVNRT groups (P>0.05). After radiofrequency, the levels of D-D, GMP-140 and TAT ablation showed an upward trend, but decreased at day 7 to reach preoperative levels. Logistic regression analysis revealed that residual slow pathway (OR=6.718, P=0.005) and inaccurate targeting (OR=2.815, P=0.007) were independent risk factors for postoperative recurrence (P<0.05). Although radiofrequency ablation can damage the cardiac vagal nerve, resulting in an increase in the heart rate after ablation during the course of the tilt table test and changed hemagglutination state within one week after ablation, those changes returned to normal after one week. The efficacy of radiofrequency ablation in the treatment of pediatric SVT is clear, and recurrence rate is low. Residual slow pathway and inaccurate targeting were independent risk factors for postoperative recurrence.
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Affiliation(s)
- Chunli Li
- Department of Cardiovascular Medicine, The Affiliated Children's Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China
| | - Libo Jia
- Department of Cardiovascular Medicine, The Affiliated Children's Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China
| | - Zhenzhou Wang
- Department of Cardiovascular Medicine, The Affiliated Children's Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China
| | - Ling Niu
- Department of Cardiovascular Medicine, The Affiliated Children's Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China
| | - Xinjiang An
- Department of Cardiovascular Medicine, The Affiliated Children's Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China
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Zhou Q, Huang F, He Z, Zuo MZ. Clinicopathological and prognostic significance of platelet count in patients with ovarian cancer. Climacteric 2017; 21:60-68. [PMID: 29231068 DOI: 10.1080/13697137.2017.1406911] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
AIM Increasing evidence indicates that platelet count is a useful biomarker of long-term outcomes in patients with ovarian cancer. However, the prognostic value of platelet count in patients with ovarian cancer remains controversial. We therefore conducted a meta-analysis aimed to investigate the prognostic role of the platelet count in patients with ovarian cancer. METHOD A comprehensive search was performed from the databases of PubMed, Embase and the Cochrane Library until June 20, 2017. A total of 18 studies with 6754 patients were included. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) and odds ratios and 95% CIs from each study were pooled. RESULTS The results demonstrated that elevated pretreatment platelet count was significantly related to poor survival from ovarian cancer; the pooled HRs for overall, progression-free and disease-free survival were 1.81 (95% CI 1.52-2.15), 1.48 (95% CI 1.24-1.75) and 1.39 (95% CI 1.19-1.61), respectively. Subgroup analyses were divided by ethnicity, sample size, FIGO stage, cut-off value of the platelet count, analysis method and Newcastle Ottawa Scale score, but the results did not show any significant change in the main results. Increased platelet count was also significantly associated with the FIGO stage, tumor differentiation, ascites, residual tumor mass, CA125 level, recurrence and metastasis. CONCLUSION This meta-analysis revealed that an elevated platelet count pretreatment denotes a predictive factor of poor prognosis and unfavorable clinicopathological parameters for ovarian cancer patients.
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Affiliation(s)
- Q Zhou
- a Department of Gynecology and Obstetrics , The People's Hospital of Three Gorges University/The First People's Hospital of Yichang , Yichang , China
| | - F Huang
- a Department of Gynecology and Obstetrics , The People's Hospital of Three Gorges University/The First People's Hospital of Yichang , Yichang , China
| | - Z He
- a Department of Gynecology and Obstetrics , The People's Hospital of Three Gorges University/The First People's Hospital of Yichang , Yichang , China
| | - M-Z Zuo
- a Department of Gynecology and Obstetrics , The People's Hospital of Three Gorges University/The First People's Hospital of Yichang , Yichang , China
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Mege D, Crescence L, Ouaissi M, Sielezneff I, Guieu R, Dignat-George F, Dubois C, Panicot-Dubois L. Fibrin-bearing microparticles: marker of thrombo-embolic events in pancreatic and colorectal cancers. Oncotarget 2017; 8:97394-97406. [PMID: 29228619 PMCID: PMC5722571 DOI: 10.18632/oncotarget.22128] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 08/04/2017] [Indexed: 12/16/2022] Open
Abstract
Background Microparticles (MPs) are plasma membrane-derived extracellular vesicles present in the bloodstream. We have described a specific signature of MPs, called microparticulosome, in colorectal (CRC) and pancreatic (PC) cancers. We observed that levels of fibrin-bearing MPs were significantly increased in patients suffering from PC and CRC in comparison with control groups. Here, we hypothesised that fibrin-MPs may constitute a relevant biomarker of thrombosis associated with cancer. The objective was to compare the microparticulosome signature between patients presenting with thrombo-embolic event and those without. Methods Patients with CRC and PC were prospectively included and divided in those with thrombo-embolic events (Group A) and those without (Group B). MPs were analyzed by flow cytometer, combining the analysis of Annexin V-positive with characterization of their origin and determination of their procoagulant activities. D-dimer levels were measured in the same samples. Results We included 118 patients, divided in 19 patients with thrombo embolic event and 99 patients without. Fibrin-bearing MPs levels were significantly higher in presence of thrombo-embolic events, contrary to D-dimers levels. Fibrin-bearing MPs were more frequently produced by erythrocytes, endothelial cells or Ep-CAM+cells than platelets or leukocytes. Overall survival was shorter in case of thrombo-embolic events than without. The most frequent genes expressed by MPs derived from PC or CRC were implicated in metastatic diffusion of tumor cells, drug resistance, coagulation and inflammation. Conclusion Circulating MPs, particularly fibrin-bearing MPs, could be used as a new biomarker to predict cancer-associated thrombo-embolic events and poor survival.
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Affiliation(s)
- Diane Mege
- Aix Marseille Univ, INSERM UMR-S1076, VRCM, Marseille, France.,Department of digestive surgery, Timone University Hospital, Marseille, France
| | - Lydie Crescence
- Aix Marseille Univ, INSERM UMR-S1076, VRCM, Marseille, France
| | - Mehdi Ouaissi
- Department of digestive surgery, Timone University Hospital, Marseille, France
| | - Igor Sielezneff
- Aix Marseille Univ, INSERM UMR-S1076, VRCM, Marseille, France.,Department of digestive surgery, Timone University Hospital, Marseille, France
| | - Regis Guieu
- Aix Marseille Univ, UMR MD2, Laboratory of Biochemistry, Timone University Hospital, Marseille, France
| | - Françoise Dignat-George
- Aix Marseille Univ, INSERM UMR-S1076, VRCM, Marseille, France.,Laboratory of Hematology, Conception University Hospital, Marseille, France
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Liu Z, Guo H, Gao F, Shan Q, Li J, Xie H, Zhou L, Xu X, Zheng S. Fibrinogen and D-dimer levels elevate in advanced hepatocellular carcinoma: High pretreatment fibrinogen levels predict poor outcomes. Hepatol Res 2017; 47:1108-1117. [PMID: 27914119 DOI: 10.1111/hepr.12848] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Revised: 11/21/2016] [Accepted: 11/27/2016] [Indexed: 12/22/2022]
Abstract
AIM Plasma fibrinogen and D-dimer have been reported to predict survival in several types of malignancies. The aim of this study is to investigate their predictive value in patients with hepatocellular carcinoma (HCC). METHODS We retrospectively analyzed plasma fibrinogen and D-dimer levels from 252 subjects: control (n = 20), hepatitis (n = 20), cirrhosis (n = 20), and HCC (n = 192) subjects. The clinical involvement and prognostic value of fibrinogen and D-dimer was analyzed in HCC subjects. To confirm the effects of tumor on hypercoagulability and fibrinolysis, fibrinogen and D-dimer levels were measured in nude mice following HCC inoculation. RESULTS Fibrinogen decreased and D-dimer increased in cirrhosis subjects relative to other groups. In HCC subjects, elevated fibrinogen and D-dimer levels were significantly associated with adverse tumor features (increased size, stage, and grade) and systemic inflammation. Patients with HCC with either elevated fibrinogen or D-dimer levels had significantly higher 3-year tumor recurrence rates (65% vs. 41%, P < 0.001 for fibrinogen; 67% vs. 40%, P = 0.011 for D-dimer) and significantly lower 3-year overall survival rates (57% vs. 79%, P < 0.001 for fibrinogen; 56% vs. 80%, P = 0.001 for D-dimer). After multivariate analysis, elevated fibrinogen levels remained an independent predictor of poor prognosis in HCC patients. Finally, elevated levels of fibrinogen and D-dimer were confirmed in nude mice following tumor inoculation. CONCLUSION The fibrinogen and D-dimer levels, elevating after carcinogenesis, may serve as simple but effective predictors of adverse tumor profiles and outcomes in HCC.
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Affiliation(s)
- Zhikun Liu
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Haijun Guo
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Feng Gao
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Qiaonan Shan
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Jie Li
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Haiyang Xie
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Lin Zhou
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China
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Yang X, Zhang H, Kong F, Wang G, Gu Q, Zhao Z, Li T, Ren M, Li Z, Guo Y. Effect of Huisheng oral solution on coagulation function in perioperative period in patients with primary lung cancer. J Thorac Dis 2017; 9:1891-1902. [PMID: 28839987 PMCID: PMC5542976 DOI: 10.21037/jtd.2017.06.64] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 06/01/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND The incidence of venous thromboembolism (VTE) is about 4-10% in lung cancer patients. Huisheng oral solution (HSOS) has been previously demonstrated to inhibit carageenan induced acute thrombosis in rats, reduce the incidence of thrombosis in the lungs and mesentery of tumor-bearing mice and inhibit tumor cell metastasis. The purpose of this study was to assess the anticoagulant effect of HSOS in lung cancer patients in the perioperative period. METHODS This study was a multicenter, randomized, single-blind, blank-controlled clinical trial. A total of patients at five hospitals in Hebei Province, China were included. The patients were randomly divided into study group or control group according to random number table. The primary outcome was the blood test indices in both groups. The study group was given oral HSOS (20 mL, bid) from admission until 24 h before surgery. If no active bleeding was observed, the patients were given oral HSOS (20 mL, tid) from 24 h to 24 d postoperatively. The patients in the study group did not receive any other anticoagulation therapy during the study period and the control group only underwent surgery. The study protocol was approved by the local ethics committee of principal investigator hospital. Blood samples were taken at admission (before therapy), 24 h, 72 h, 10 d (before discharge) and 24 d (first visit after discharge) after surgery. Routine blood tests [red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (HGB), and platelet (PLT) count] and coagulation function test [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and plasma D-dimer] were performed. The changes in outcome measures over time were analyzed by repeated measures analysis of variance to compare the differences between groups and between different time points and assess the impact of tumor stage and mode of surgery on them. All tests were two-tailed, and P values <0.05 were considered statistically significant. RESULTS The results differed between different tumor stage groups. In stage III-IV group, there was no significant difference in various indices between the study group and control group. In stage I-II group, there was significant difference in hemoglobin (P=0.004), platelet count (P=0.007), fibrinogen (P=0.046), and plasma D-dimer (24 d: P=0.032) between two groups. Fibrinogen reach the peak 72 h after surgery, and other indices reach the peak 7-10 d postoperatively and declined one month after surgery, and the decline tendency was different between two groups. In addition, no adverse drug reaction was observed in both the study group and control group. CONCLUSIONS HSOS (20 mL, tid) is of good safety profile and does not increase the risk of bleeding. With its unique characteristic of convenience for being taken, HSOS (20 mL, tid) could be a proper treatment for lung cancer patients in the perioperative period.
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Affiliation(s)
| | - Helin Zhang
- The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Fanyi Kong
- Cangzhou Central Hospital, Cangzhou 061001, China
| | - Guochen Wang
- North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China
| | - Qianyu Gu
- Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province, Shijiazhuang 050000, China
| | - Zheng Zhao
- Handan Central Hospital, Handan 056001, China
| | - Tiezhi Li
- The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Mingming Ren
- Cangzhou Central Hospital, Cangzhou 061001, China
| | - Zuosheng Li
- North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China
| | - Yang Guo
- Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province, Shijiazhuang 050000, China
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Wu J, Fu Z, Liu G, Xu P, Xu J, Jia X. Clinical significance of plasma D-dimer in ovarian cancer: A meta-analysis. Medicine (Baltimore) 2017; 96:e7062. [PMID: 28640083 PMCID: PMC5484191 DOI: 10.1097/md.0000000000007062] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 05/02/2017] [Accepted: 05/03/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND D-dimer has been widely used for the diagnosis and prognosis of ovarian cancer, but there is still controversy on its prediction value of ovarian cancer. OBJECTIVES To explore the clinical significance of plasma D-dimer level on ovarian cancer systematically. METHODS Using PubMed, Cochrane Library, and Web of Science libraries, all the relevant studies for the diagnostic and prognostic value of plasma D-dimer for ovarian cancer and the relationship between elevated D-dimer level and venous thromboembolism (VTE) risk of ovarian cancer were searched till May 30, 2016. Standardized mean difference (SMD), odds ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) were appropriately pooled. RESULTS A total of 15 eligible studies involving a total of 1437 cancer patients were included. No significant association was found between high D-dimer level and overall survival of patients with ovarian cancer (HR 1.32, 95% CI: 0.90-1.95, P = .044). However, subgroup analysis indicated that the sample sizes could explain the heterogeneity between studies. And elevated D-dimer could predict increased risk of mortality when the sample sizes were >100 (HR 1.800, 95% CI: 1.283-2.523, P = .845). Besides, plasma D-dimer level was significantly higher in malignant ovarian cancer patients compared with benign controls (SMD 0.774, 95% CI: 0.597-0.951, P = .39), higher in advanced ovarian cancer patients (International Federation of Gynecology and Obstetrics [FIGO] classification III and IV) than in early stage ovarian cancer patients (FIGO classification I and II, SMD 0.611, 95% CI: 0.373-0.849, P = .442). And high D-dimer level indicated high VTE risk (OR 4.068, 95% CI: 2.423-6.829, P = .629) of ovarian cancer patients. CONCLUSION The plasma D-dimer level in ovarian cancer patients can predict the changes that correlated with disease progression and the VTE risk. But its predictive value for the prognosis of ovarian cancer was significantly dependent on the sample sizes. More well-designed studies with large sample sizes are needed to validate and update the findings of present study.
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Affiliation(s)
- Jiacong Wu
- Nantong Maternity and Child Health Care Hospital, Nantong
| | - Ziyi Fu
- Nanjing Maternity and Child Health Medical Institute, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing
| | - Guangquan Liu
- Department of Obstetrics and Gynecology, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Pengfei Xu
- Nanjing Maternity and Child Health Medical Institute, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing
| | - Juan Xu
- Department of Obstetrics and Gynecology, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Xuemei Jia
- Department of Obstetrics and Gynecology, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China
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Xu L, He F, Wang H, Gao B, Wu H, Zhao S. A high plasma D-dimer level predicts poor prognosis in gynecological tumors in East Asia area: a systematic review and meta-analysis. Oncotarget 2017; 8:51551-51558. [PMID: 28881667 PMCID: PMC5584268 DOI: 10.18632/oncotarget.17936] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 02/15/2017] [Indexed: 12/14/2022] Open
Abstract
High pre-treatment plasma D-dimer levels have been reported as a factor associated with a poor prognosis in different types of malignancies, including pancreatic, gastric, colorectal, lung, and nasopharyngeal carcinoma. Here, we performed a meta-analysis to determine the association of plasma D-dimer levels and long term survival in gynecological cancers, including ovarian, cervical and endometrial carcinoma. We searched all eligible publications in PubMed and Web of Science Databases up to August 2016. Primary outcomes, including overall survival (OS), disease-free survival and hazard ratios (HR) of were extracted and analyzed. Heterogeneity and publication bias were also assessed. A total of 7 eligible studies with 1112 cases were included in this study and all included studies are conducted in East Asia area. We found that gynecological cancer patients with high D-dimer demonstrates a much lower 5-year survival rate than those with low D-dimer levels (OR 4.12, 95% CI 3.04-5.58, P<0.00001). No significant heterogeneity is found (I2 = 10 %; P = 0.35). Importantly, pooled analysis showed that high plasma D-dimer levels are predictive of a shorter OS in gynecological cancers (HR 2.09, 95% CI 1.59-2.74). No heterogeneity is observed (I2=5%, P=0.39). Additionally, a subgroup analysis of ovarian cancer is conducted. In conclusion, this meta-analysis showed that a high plasma D-dimer level predicts poor prognosis in gynecological tumors.
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Affiliation(s)
- Lei Xu
- Gynecology Department, Qingdao University Affiliated Qingdao Women's and Children's Hospital, Qingdao, China.,Gynecology Department, Maternal and Child Health Hospital of Zibo City, Shandong, China
| | - Fan He
- Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Hongcai Wang
- Gynecology Department, Maternal and Child Health Hospital of Zibo City, Shandong, China
| | - Bei Gao
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Huini Wu
- Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Shuping Zhao
- Gynecology Department, Qingdao University Affiliated Qingdao Women's and Children's Hospital, Qingdao, China
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Luo Y, Kim HS, Kim M, Lee M, Song YS. Elevated plasma fibrinogen levels and prognosis of epithelial ovarian cancer: a cohort study and meta-analysis. J Gynecol Oncol 2017; 28:e36. [PMID: 28382799 PMCID: PMC5391395 DOI: 10.3802/jgo.2017.28.e36] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 01/06/2017] [Accepted: 02/08/2017] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE To evaluate the effect of elevated plasma fibrinogen levels on the prognosis of epithelial ovarian cancer (EOC). METHODS We reviewed the data of 217 patients with advanced-stage EOC between 2000 and 2012, and investigated the prognostic role of elevated plasma fibrinogen levels compared with serum CA-125 levels, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). For further evaluation, we performed a meta-analysis using 5 cohort studies published to July 2015, including our cohort study after a literature review. RESULTS Among the four biomarkers, only plasma fibrinogen levels >485.2 mg/dL were correlated with impaired progression-free survival (PFS) and overall survival (OS) (median, 13.9 vs. 20.3 months and 42.2 vs. 55.4 months; p<0.010). Elevated plasma fibrinogen levels were an independent factor for poor PFS with marginal significance and OS (adjusted hazard ratios [HRs]=1.389 and 1.581; 95% confidence intervals [CIs]=0.979-1.972 and 1.032-2.423, respectively). Furthermore, crude and subgroup meta-analyses demonstrated that elevated plasma fibrinogen levels were associated with impaired PFS and OS in patients with all stage EOC. CONCLUSION Elevated plasma fibrinogen levels be more important for predicting survival than serum CA-125 levels, NLR and PLR in patients with EOC, in particular, advanced-stage disease. Moreover, it may be related to poor prognosis of EOC.
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Affiliation(s)
- Yanlin Luo
- Department of Gynecologic Oncology, Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Miseon Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoungnam, Korea
| | - Maria Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Yong Sang Song
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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Lee S, Huh SJ, Oh SY, Koh MS, Kim SH, Lee JH, Han JY, Choi HJ, Kim SJ, Kim HJ. Clinical significance of coagulation factors in operable colorectal cancer. Oncol Lett 2017; 13:4669-4674. [PMID: 28599468 PMCID: PMC5452961 DOI: 10.3892/ol.2017.6058] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 02/17/2017] [Indexed: 12/27/2022] Open
Abstract
Abnormal hemostasis in cancer patients has prev iously been studied. The primary objective of the present study was to evaluate the association between preoperative hemostasis markers and clinicopathological parameters, and to identify a hemostasis marker affecting survival in patients following curative resection for colorectal cancer. A total of 170 patients who underwent curative surgery for colorectal carcinoma were evaluated. Preoperative coagulation tests included platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and fibrinogen degradation product (FDP). The clinicopathological variables, including age, gender, tumor location (rectum/colon), tumor size (≥5 cm vs. <5 cm), depth of tumor invasion, lymph node metastasis, stage, lymphovascular invasion, margin involvement and histological differentiation were analyzed. The median age of analyzed patients was 63 years (range, 28-84). The male to female ratio was 62:38. Increased levels of plasma fibrinogen, PT and platelet count (PLT) were associated with larger tumor size (P<0.001, P=0.015 and P=0.002, respectively). Increased plasma fibrinogen levels were significantly associated with depth of tumor invasion and stage (P=0.014 and P=0.048, respectively). Increased plasma D-dimer and FDP levels were significantly associated with tumor node metastasis stage (P=0.031 and P=0.002, respectively). Prolonged PT level (≥11.7 sec), hyper-fibrinogenemia (≥327 mg/dl), high D-dimer level (≥1.3 µg/ml) and increased FDP level (≥2.7 µg/ml) were the prognostic factors associated with shorter survival. Preoperative plasma fibrinogen level was significantly associated with tumor size and depth of tumor invasion. Preoperative plasma prolonged PT level, hyperfibrinogenemia, high D-dimer level and increased FDP level may function as hemostasis markers that predict overall survival in operable patients with colorectal cancer.
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Affiliation(s)
- Suee Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Seok Jae Huh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Myeong Seok Koh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Sung-Hyun Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Ji Hyun Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Jin Young Han
- Department of Laboratory Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Hong Jo Choi
- Department of Surgery, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Su Jin Kim
- Department of Pathology, Dong-A University College of Medicine, Busan 49201, Republic of Korea
| | - Hyo-Jin Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea
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Cui J, Yu M, Zhang N, Wang S, Zhu Y, Chen S, Zhu K, Du J, Zhao H, Liu X, Chen P, Wang W, Zhang D, Shi B. Prognostic scores based on the preoperative plasma fibrinogen and serum albumin level as a prognostic factor in patients with upper urinary tract urothelial carcinoma. Oncotarget 2017; 8:68964-68973. [PMID: 28978171 PMCID: PMC5620311 DOI: 10.18632/oncotarget.16483] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 03/15/2017] [Indexed: 01/12/2023] Open
Abstract
This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p<0.001; HR=5.521, 95%CI 2.074-14.697, p=0.001, respectively) was an independent predictor for overall survival and cancer specific survival. The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting overall survival and cancer specific survival in UTUC. The fibrinogen and albumin levels are low cost and easy accessibility in clinical practice.
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Affiliation(s)
- Jianfeng Cui
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Meng Yu
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Ning Zhang
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Shiyu Wang
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Yaofeng Zhu
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Shouzhen Chen
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Kejia Zhu
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Jian Du
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Hongda Zhao
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Xigao Liu
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Pengxiang Chen
- Department of Radiation Oncology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Wenbo Wang
- School of Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Dongqing Zhang
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Benkang Shi
- Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China
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50
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Swier N, Versteeg HH. Reciprocal links between venous thromboembolism, coagulation factors and ovarian cancer progression. Thromb Res 2016; 150:8-18. [PMID: 27988375 DOI: 10.1016/j.thromres.2016.12.002] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 11/23/2016] [Accepted: 12/03/2016] [Indexed: 02/06/2023]
Abstract
Ovarian cancer is the most lethal gynecological malignancy, which is due to late presentation. Treating advanced stage ovarian cancer is difficult, and tumor recurrence and chemoresistance frequently occur. In addition, early detection remains a major challenge as there are no early warning signs and no appropriate biomarkers. To reduce mortality rates of ovarian cancer patients, novel drug targets and biomarkers are needed. We postulate that hemostatic keyplayers are of importance when combatting ovarian cancer. The majority of ovarian cancer patients have abnormal hemostatic blood serum marker levels, which indicate an activated coagulation system. This makes patients more prone to experiencing venous thromboembolism (VTE), and the occurrence of VTE in ovarian cancer patients adversely affects survival. Coagulation activation also promotes tumor progression as it influences tumor biology at several stages and the decreased survival rates associated with ovarian cancer-associated thrombosis are more likely due to cancer metastasis rather than to fatal thromboembolic events. In this review, we will discuss; (1) Population studies that address the bidirectional relationship between VTE and ovarian cancer, and the most important risk factors involved; (2) The mechanisms of coagulation factors and platelets that are critically involved in the development of VTE, and the progression of ovarian cancer; (3) Roles and future directions of coagulation factors in ovarian cancer therapy, and in diagnosis and prognosis of ovarian cancer as biomarkers.
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Affiliation(s)
- Nathalie Swier
- Department of Internal Medicine, Thrombosis and Hemostasis Division, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands
| | - Henri H Versteeg
- Department of Internal Medicine, Thrombosis and Hemostasis Division, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
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