**5. Fibrinogen and D-dimers in pancreatic ductal adenocarcinoma**

Extensive alterations of blood clotting have been demonstrated in pancreatic cancer patients. Sun et al. characterised different coagulation parameters in 139 patients diagnosed with pancreatic cancer and compared the data to forty age- and gender-matched controls. Cancer patients had significantly higher level of fibrinogen (p < 0.01), D-dimers (p < 0.01), antithrombin III (p = 0.015), factor VIII (p < 0.01), as well as increased international normalised ratio (p = 0.022), longer prothrombin time (p < 0.01) and prolonged activated partial thromboplastin time; p < 0.01 [73].

by preoperative imaging, high preoperative level of D-dimers might suggest the presence of occult liver metastases or unresectability of other cause, and the surgery should be started with diagnostic laparoscopy in contrast to laparotomy that might turn out to become explor-

Systemic Inflammatory Response in Pancreatic Ductal Adenocarcinoma

http://dx.doi.org/10.5772/intechopen.78954

19

Considering the complexity of carcinogenesis and inflammation, any single parameter has limitations and shortcomings, reflected in the controversial reports. To improve the efficacy

In advanced PDAC, several teams have explored the combination of baseline NLR and dynamics upon the influence of chemotherapy [32]. The baseline value is scored as high or low in regard to threshold level. The cut-offs in SIR studies frequently are identified by ROC analysis or by median value. The dynamics is scored as either increase or decrease in response to the treatment; ratio between NLR in a predefined time point during treatment versus pre-treatment NLR (ratio < 1 is analogous to decrease) or high versus low value (against the threshold) in a predefined time point during treatment. The score is based on the count of

Combined SIR scores have been generated, including NLR and other SIR parameters. The results might be assessed by the count of adverse prognostic factors, for example high NLR or another parameter that exceeds the cut-off level. Summary score including NLR and PLR is the most obvious option that has been already successfully tested in other cancers, for example, gastric carcinoma [14]. This approach has been fruitful also in PDAC. In patients with locally advanced pancreatic cancer treated by chemoradiotherapy, it was noted that the combination of both elevated NLR and PLR is associated with especially low 1-year survival rate and 1-year progression-free survival rate [30]. Other combinations have been evaluated as well, for example, NLR and blood counts of regulatory T lymphocytes in resectable PDAC [79]. Combined index based on hypoalbuminemia and NLR has been advocated to evaluate the prognosis of gastric cancer [80]. Analogously, in patients receiving stereotactic radiotherapy for advanced PDAC, high NLR (>5) and low albumin levels were associated with shorter

Currently, there are only few data suggesting dependence of NLR on the tumour burden. The correlations with pT or size have been reported with some authors while corroborated by others.

adverse prognostic factors: high baseline NLR or increase of NLR upon treatment.

**6. Complex SIR-based scores in pancreatic ductal adenocarcinoma:** 

of SIR parameters, combinations of those have been tested.

**6.1. Combination of baseline and dynamic estimates of NLR**

atory laparotomy only.

**presence and future**

**6.2. NLR and other SIR parameters**

median overall survival [35].

**6.3. NLR and cancer burden**

Plasma fibrinogen levels are significantly higher in pancreatic cancer than in case of benign pancreatic tumours [74]. Hyperfibrinogenemia has been observed in 24.8% [19]–41.1% of pancreatic cancer patients [74]. In pancreatic cancer patients, levels of fibrinogen and D-dimers are higher before surgery, but significantly lower at the recurrence-free period after surgery; p < 0.01 [75]. Fibrinogen level in pancreatic cancer also correlates with NLR and PLR and shows negative correlation with lymphocyte to monocyte ratio [76]. Thus, in pancreatic tumours, hyperfibrinogenemia is associated with malignant course, depends on cancer presence in the body and correlates with SIR parameters. Therefore, elevated fibrinogen level can be considered a component of cancer-induced SIR. It is associated with patient's prognosis.

In 96 patients who underwent chemoradiotherapy for histologically confirmed, locally advanced PDAC, elevated fibrinogen level (≥400 mg/dL) was an independent predictor of worse overall and progression free survival [69]. Similarly, in 321 patients with locally advanced or metastatic pancreatic adenocarcinoma, high plasma fibrinogen was associated with shorter survival. It was confirmed an independent prognostic factor [76]. Wang et al. [19] also noted the association between higher levels of fibrinogen and worse prognosis. However, controversies remain. For instance, elevated preoperative concentrations of D-dimers but not fibrinogen were associated with shorter overall and progression-free survival in the study of Cao et al. [77].

In PDAC, plasma fibrinogen levels increase along with higher stage. In 125 PDAC patients, higher mean fibrinogen concentration was found in stage III/ IV patients compared to those diagnosed at stage I/II. Higher levels of fibrinogen correlated with the presence of distant metastasis [19, 74].

D-dimers represent another blood clotting parameter that is widely studied in pancreatic cancer, including the prognostic role. Thus, elevated preoperative concentrations of D-dimers were associated with shorter overall and progression-free survival [77]. D-dimers also reflect tumour burden. Higher D-dimer levels in plasma were associated with higher stage and grade [73].

Higher concentration of D-dimers predicts shorter survival and non-resectability [75]. The association between non-resectability and elevated D-dimer levels in peripheral blood was also confirmed by Durczynski et al. [78] who assessed 64 patients. The concentration of D-dimers was higher in those who had metastatic cancer in comparison with patients suffering from locally advanced disease [78]. Thus, if the pancreatic tumour seems resectable by preoperative imaging, high preoperative level of D-dimers might suggest the presence of occult liver metastases or unresectability of other cause, and the surgery should be started with diagnostic laparoscopy in contrast to laparotomy that might turn out to become exploratory laparotomy only.
