Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUND Inflammation plays an important role in tumor progression,and growing evidence has confirmed that the fibrinogen-to-albumin ratio(FAR)is an important prognostic factor for overall survival in malignant tumors.AIM To investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma(PDAC).METHODS We retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019.The surv_cutpoint function of the R package survminer via RStudio software(version 1.3.1073,http://www.rstudio.org)was used to determine the optimal cut-off values of biological markers,such as preoperative FAR.The Kaplan-Meier method and log-rank tests were used for univariate survival analysis,and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTS The optimal cut-off value of FAR was 0.08 by the surv_cutpoint function.Higher preoperative FAR was significantly correlated with clinical symptoms(P=0.001),tumor location(P<0.001),surgical approaches(P<0.001),preoperative plasma fibrinogen concentration(P<0.001),and preoperative plasma albumin level(P<0.001).Multivariate analysis showed that degree of tumor differentiation(P<0.001),number of metastatic lymph nodes[hazard ratio(HR):0.678,95%confidence interval(CI):0.509-0.904,P=0.008],adjuvant therapy(HR:1.604,95%CI:1.214-2.118,P=0.001),preoperative cancer antigen 19-9 level(HR:1.740,95%CI:1.288-2.352,P<0.001),and preoperative FAR(HR:2.258,95%CI:1.720-2.963,P<0.001)were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSION The increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC.Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection

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.

Advances in understanding the molecular mechanism of pancreatic cancer metastasis

BACKGROUND： Pancreatic cancer（PC） is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis.DATA SOURCES： Relevant articles on PC metastasis were searched in MEDLINE via Pub Med prior to April 2015. The search was limited in English publications.RESULTS： PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inflammation, stress response, and circulating tumor cells.CONCLUSIONS： Analyses of relevant gene functions and signaling pathways are needed to establish the gene regulatory network and to define the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of personalized therapy by identifying specific markers and targets.