At present, surgery is still the only curative treatment for pancreatic cancer. An increasing number of studies have shown that VTE is an important cause of postoperative mortality and the second leading cause of death in cancer patients [3, 15, 16]. For patients with BRPC, the tumor is more aggressive and the length of surgery is longer, which also means a higher risk of VTE. Therefore, we conducted this study to explore the prevalence and related factors of VTE after BRPC, and to construct a VTE prediction model, which attracted the attention of clinicians and also provided a reference for screening people at high risk of VTE in clinical work. The incidence of VTE in the present study was 45.9%. Age, ALB, operation time, tumor diameter and preoperative D-dimer were independent related factors.
Multiple patient related risk factors consistent with activation of coagulation and contributing significantly to the risk of VTE in cancer patients, including age, gender, race, common comorbidities, etc [17, 18]. In this study, we obtained similar results that age (OR: 1.076, 95% CI: 1.024-1.131, P=0.004) is an independent risk factor for VTE in patients after BRPC surgery. In addition, this study concluded that patients' preoperative plasma ALB level was a protective factor. Previous studies have shown that cancer patients with lower serum ALB levels have a significantly increased risk of VTE and death compared to cancer patients with higher serum ALB levels [19]. The study showed that ALB was less than 44.2 g/L, the risk of VTE increased approximately 2-fold, and the risk of VTE continued to increase with decreasing ALB levels. BRPC patients often suffer from hypoproteinemia due to poor digestive function and tumor consumption resulting in malnutrition. This increases the risk of developing VTE perioperatively. At the same time, the mechanisms involved also need to be explored by further studies.
The risk of developing VTE is most influenced by recent surgery. In the Olmstead County series, patients who had recently been hospitalized for surgery had a 22-fold (95% CI, 9.4-49.9) higher risk of VTE compared with those who had not recently been hospitalized or had not undergone surgery [20]. Surgery-related factors include body position, operation site, operation duration, operation method, blood loss, blood transfusion volume, vascular occlusion time, etc. For patients undergoing BRPC surgery, portal system occlusion and reconstruction are often performed during surgery, which inevitably causes local arteriovenous injury, while vascular endothelial injury exposes collagen and basement membrane, releases tissue factor (TF), promotes platelet aggregation, and leads to thrombosis [21]. Prolonged operation time will lead to prolonged recumbency, but also lead to lower limb muscle pump reflux weakened, lower limb venous dilatation in patients with venous return blocked, blood stasis, prone to VTE events. In addition, massive bleeding and blood transfusion due to complex surgery can also lead to coagulation disorders [22]. Surgery can also stimulate the body 's inflammatory response, stimulate neutrophil activation, and promote thrombosis and tumor metastasis [23, 24]. More than surgery, in cancer therapy, treatment modalities such as platinum-based chemotherapy (e.g., cisplatin) and antiangiogenic therapy (e.g., bevacizumab) are often associated with VTE [25-28]. Tumor-related factors include tumor type, primary site, cancer stage, grade and so on. It is generally believed that the types of cancer most associated with VTE are gastric and pancreatic cancers [29, 30]. More and more studies have shown that tumor cells directly or grounded to activate the coagulation process by expressing procoagulant factors, cell surface adhesion molecules, as well as activating platelets and inflammatory cells, resulting in a hypercoagulable state of the blood, thereby promoting the occurrence of VTE. On the one hand, tumor cells can secrete factors such as TF, cell adhesion molecules (I-CAM), which is directly involved in the coagulation process and promotes the formation of CAT [31-34]. On the other hand, tumor cells activate normal cells (endothelial cells, platelets, leukocytes, etc.) by synthesizing and releasing soluble regulators or adhesion, so that they undergo corresponding procoagulant changes and promote the formation of VTE [35-38]. In this study, the tumor diameter was independently associated with the occurrence of VTE and was somewhat consistent with it.
Among haematologic biomarkers, an elevated D-dimer is strongly and independently associated with VTE in cancer patients [39-41]. D-dimer is the degradation product of cross-linked fibrin, indicating the global coagulation activation and fibrinolysis. Elevated levels of D-dimer most probably reflect the hypercoagulable state (induced activation of hemostasis: effect of a low molecular weight heparin [42]. Because D-dimer levels tend to fluctuate greatly due to factors such as surgery, we selected the results of preoperative D-dimer in patients, which can also more acutely reflect the coagulation status of patients. The results showed that preoperative D-dimer level (OR: 9.227, 95% CI: 1.062-80.126, P=0.044) was an independent risk factor for VTE in patients undergoing BRCP surgery. In addition, other biomarkers independently associated with VTE in cancer patients including plasma soluble P-selectin (sP-selectin) and prothrombin fragment 1 + 2 (F1 + 2), are also worthy of further study.
The Caprini RAM is often used to assess VTE risk in patients after surgical procedures [43]. However, all patients undergoing BRPC surgery were at high risk of Caprini RAM, which also means that Caprini RAM does not distinguish well between this truly high-risk group. Therefore, in this study, we constructed a nomogram based on the independent factors derived from the analysis in order to help clinicians identify people at high risk of VTE and provide a reference for the next step of VTE prevention.
Our study also has some limitations as follows. First, this was a single-center retrospective study and the study results required external validation. Second, the study sample size is small, because of the difficulty of surgery, difficulty in obtaining allogeneic vessels and other reasons, a multicenter study with a large sample size is still needed to further explore in the future. Finally, this study included patients who underwent BRPC surgery, so whether the results could be applicable in other types of patients also needs to be confirmed by more studies.