Prognostic Impact of Coagulation Activity in Patients Undergoing Curative Resection for Pancreatic Ductal Adenocarcinoma

Abstract

Background/Aim: The aim of this study was to elucidate the clinical impact of coagulation disorders on outcomes after curative resection of pancreatic ductal adenocarcinoma. Patients and Methods: Preoperative coagulation activity in 135 patients, who had undergone curative resections for pancreatic ductal adenocarcinoma was retrospectively evaluated and the impact on survival outcomes analyzed. Results: A prolonged prothrombin timeinternational normalized ratio (PT-INR) (≥1.1) was detected in 23/135 patients (17%). Univariate analysis that showed prolonged PT-INR was associated with worse relapse-free (hazard ratio=1.79, p=0.044) and overall (hazard ratio=2.18, p=0.004) survival. Multivariate analyses showed prolonged PT-INR, large tumor (>30 mm), and lymph node metastasis were independent predictors of poor overall survival. Conclusion: Prolonged PT-INR may be a predictor of poor prognosis in patients with pancreatic ductal adenocarcinoma who have undergone curative resection. Coagulation disorders may be a therapeutic target for improving outcomes of pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma (PDAC) comprises 85% of pancreatic cancer cases and remains one of the most common and aggressive malignancies, with a 5-year survival rate of approximately 20% despite improvements in achieving macroscopically curative resection with surgical procedures and adjuvant chemotherapy (1). Several clinical trials have shown that neoadjuvant therapies can prolong survival in patients with PDAC because such therapies can down-stage PDAC and thus improve the curative resection rate. However, it remains to be determined which regimen is the most suitable for PDAC according to each patient's clinical, genetic, and performance status (2). To improve selection of treatment strategies for PDAC and its outcomes, prognostic biomarkers that can be measured easily and reliably are needed to optimally evaluate tumor aggressiveness. A close association between cancer biology and coagulation disorders that has an impact on tumor progression has been reported (3). Hypercoagulability is more likely to occur in patients with pancreatic cancer than in those with other types of cancer (4). Patients with pancreatic cancer are predisposed to developing venous thromboembolic events (VTEs) (5). VTEs in patients with cancer are caused by hypercoagulable states and associated with a poor prognosis (6). Pancreatic resection is also associated with VTEs (7). In patients with hepatocellular carcinoma, coagulation disorders are associated with various complications and poor prognosis (8). Increased fibrinogen, fibrin split products, and D-dimer levels have been associated with worse survival outcomes in patients with breast and colorectal cancer (9-11). In patients with lung cancer, a prolonged prothrombin time-international normalized ratio (PT-INR) was found to be associated with worse survival outcomes (12). However, the clinical impact of coagulation disorders in PDAC is still unclear. Therefore, the purpose of this study was to ...

Association between PT, PT-INR, and in-hospital mortality in critically ill patients with tumors: A retrospective cohort study

“…( 15 ) In addition, extended PT-INR was related to shortened recurrence-free survival and overall survival, rendering it a predictive factor of overall survival in patients with pancreatic ductal adenocarcinoma who had undergone curative resection. ( 16 ) Our findings are somewhat compatible with the aforementioned findings; specifically, a greater PT-INR was shown to be related to an increased risk of in-hospital mortality in critically ill patients with tumors who were treated in the ICU. In contrast to previous investigations, our study cohort consisted of severely ill individuals with tumors, and the previous research findings cannot be generalized to this patient group, as it consists of diverse kinds of malignancies rather than specific malignancies in previous studies.…”

Construction and Validation of a Recurrent Risk Nomogram Model for Non-Small Cell Lung Cancer within 1 Year after Radical Resection

“…D-dimer was the end product of fibrinolytic degradation catalyzed by a fibrinolytic enzyme, which could reflect the synthesis status of fibrinolytic enzyme and thrombin in the body, and the increase of its level indicated the existence of hypercoagulability and secondary fibrinolytic hyperactivity in the body [ 15 ]. The increase of plasma D-dimer after surgery suggested that the patient's coagulation and fibrinolysis system were dysfunctional, and abnormal coagulation could induce tumor recurrence [ 16 ]. In addition, D-dimer was generally low in healthy people but high in lung cancer patients, and its level increased with the increase of TNM stage [ 17 ].…”

PANC-1 Cell Line as an Experimental Model for Characterizing PIVKA-II Production, Distribution, and Molecular Mechanisms Leading to Protein Release in PDAC

“…Although many serum markers for the diagnosis of PDAC have been evaluated, to date, no reliable biomolecules (such as CEA, CA19.9, CA242) [ 30 ] have been identified for optimal clinical management. A notable push in this direction has been provided by recent studies focused on new biomolecules showing more reliable diagnostic performance [ 6 , 31 , 32 ]. Among these, the most promising is PIVKA-II protein, a modified prothrombin whose expression is related to vitamin K deficiency.…”

“…In this scenario, circulating biomarkers, due to their availability, repr a powerful tool for early-stage diagnosis, prognosis, and follow up. Although many s markers for the diagnosis of PDAC have been evaluated, to date, no reliable biomole (such as CEA, CA19.9, CA242) [30] have been identified for optimal clinical managem A notable push in this direction has been provided by recent studies focused on new molecules showing more reliable diagnostic performance [6,31,32]. Among these, the…”