Prognostic Significance of Plasma Fibrinogen/Serum Albumin Ratio in the Postoperative Outcome of Pancreatic Ductal Adenocarcinoma

Patients and Methods

Ethics approval and informed consent. The procedures followed were in accordance with the ethical standards of the Institutional Review Board of Tokyo Medical University Hachioji Medical Center (T2020-0049) and with the Helsinki Declaration of 1975, as revised in 1983. Informed consent was obtained from all patients.

Patients. We retrospectively analysed clinical data of 111 patients who underwent surgical resection and had a postoperative histopathological diagnosis of PDAC at the Tokyo Medical University Hachioji Medical Center between July 2007 and May 2020. Patients with a histological diagnosis other than adenocarcinoma, including intraductal papillary mucinous carcinoma, neuroendocrine carcinoma, or benign tumour, were excluded. Patients with unresectable PDAC as per National Comprehensive Cancer Network (NCCN) guidelines (11) (distant metastasis or locally advanced tumour) were also excluded; only patients with resectable or borderline resectable PDA were included in our analysis. Additionally, we excluded patients who underwent neoadjuvant therapy (n=11) and those without preoperative fibrinogen or albumin assessments (n=33). We excluded neoadjuvant therapy patients because the proper evaluation timing of the FA score is unclear in these patients. After applying these criteria, 67 patients were eligible for inclusion.

Preoperative evaluation. A preoperative blood test was performed as close as possible to the time of surgery. All patients with obstructive jaundice and signs of cholangitis underwent biliary decompression before surgery. Endoscopic retrograde cholangiopancreatography was most often performed for bile reduction, and an endoscopic retrograde biliary drainage tube, metallic stent, or endoscopic naso-biliary drainage tube was inserted. No patients had signs of cholangitis at the time of surgery. Multiple prognostic indexes including the CAR (4), FA score, GPS (5), PLR (7), and PNI (12) were calculated based on blood tests. The FA score was calculated as follows: fibrinogen (mg/dl)/albumin (g/dl).

Surgical information. The resectability status (resectable and borderline resectable) was defined based on the NCCN guidelines (11). “Resectable” was defined as having no arterial superior mesenteric vein or portal vein contact, or as ≤180° contact without vein contour irregularity. “Borderline resectable” was defined as having more contact than a resectable tumour, but less than an unresectable tumour.

Pathological diagnosis. The pathological diagnosis was based on the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) guidelines (13), which include the tumour, nodes, and metastasis (TNM) classification, stage, and differentiation. Additionally, the microscopic lymphatic and venous invasion around the main tumour was evaluated in accordance with the AJCC/UICC guidelines. Microscopic histopathology including immunostaining (mainly D2-40 for lymphatic invasion and Elastica van Gieson for venous invasion) was used for diagnosis.

Postoperative course. The postoperative pancreatic fistula was graded according to the International Study Group on Pancreatic Fistula definition (14) as follows: grade A, transient fistula with no clinical impact; grade B, fistula requiring a change in management or an adjustment in the clinical pathway; grade C, fistula requiring a major change in clinical management or a deviation from the normal clinical pathway.

FA score evaluation. An FA score cut-off value was determined using a scatter plot of FA scores and postoperative survival. Two patient groups were defined based on whether the FA score was above or below the cut-off value, and patient characteristics were compared between the groups. The risk factors affecting overall survival (OS) and recurrence-free survival (RFS) were evaluated using multivariate analyses.

Statistical analysis. Continuous variables are expressed as the median and range (minimum to maximum); the Mann-Whitney U-test was used for comparisons between groups. Categorical variables are expressed as a count (%); they were compared using the chi-square test or Fisher’s exact test, as required. Univariate and multivariate analyses were performed using Cox proportional hazards regression analyses with forward-selection of the likelihood ratio. The prognosis was evaluated using the Kaplan-Meier method, and the statistical difference was evaluated using the log-rank test. Statistical tests were two-tailed, and significance was set at p<0.05. All statistical analyses were performed using IBM SPSS Statistics, version 26.0 (IBM Corp., Armonk, NY, USA).