Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Mar 27, 2021; 13(3): 279-302
Published online Mar 27, 2021. doi: 10.4240/wjgs.v13.i3.279
Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection
Li-Peng Zhang, Hu Ren, Yong-Xing Du, Xiao-Hao Zheng, Zong-Ming Zhang, Cheng-Feng Wang
Li-Peng Zhang, Hu Ren, Yong-Xing Du, Xiao-Hao Zheng, Cheng-Feng Wang, Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Zong-Ming Zhang, Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing 100073, China
Cheng-Feng Wang, State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Author contributions: Zhang LP was involved in study conception, data analysis, and production of tables, wrote the first draft, and revised it critically in light of comments from other authors; Ren H, Du YX and Zheng XH helped to collect the clinical data and followed up with the patients; Wang CF and Zhang ZM were involved in study conception and design, data interpretation, manuscript revision, and discussion; all authors approved the final version submitted.
Supported by the National Natural Science Foundation of China, No. 81972314; and the Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences, No. 2016-I2M-1-001.
Institutional review board statement: The study was reviewed and approved by the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cheng-Feng Wang, MD, Chief Doctor, Professor, Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. ywwangchengfeng@163.com
Received: November 10, 2020
Peer-review started: November 10, 2020
First decision: December 20, 2020
Revised: January 1, 2021
Accepted: January 21, 2021
Article in press: January 21, 2021
Published online: March 27, 2021
Abstract
BACKGROUND

Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies.

AIM

To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection.

METHODS

We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values.

RESULTS

The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection.

CONCLUSION

Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

Keywords: Pancreatic ductal adenocarcinoma, R0 resection, Fibrinogen, D-dimer, Prognosis, Survival

Core Tip: Both fibrinogen and D-dimer have been demonstrated to be independent predictors of overall survival (OS) in many patients with solid malignancies. We retrospectively analyzed the medical records of 282 patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical R0 resection. Our study confirms the synergistic value of fibrinogen and D-dimer in predicting OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.