Background and Aims: The texture of the pancreas is an important factor for the occurrence of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD). However, there are no objective evaluation criteria for estimating the hardness of the pancreatic texture. Studies have demonstrated that the activation of the pancreatic stellate cells (PSCs) is closely associated with the pancreatic fibrosis, and therefore, their activity may probably influence the texture of the pancreas. This study was designated to investigated the feasibility and effectiveness of using the degree of PSC activity for predicting the clinically relevant postoperative pancreatic fistula (CR-POPF) after PD. 
Methods: The surgical margin samples from 101 consecutive patients who underwent PD in the Department of Pancreatic Surgery, Xiangya Hospital, Central South University from December 2017 to September 2019 were prospectively collected. The degree of PSC activity was determined and graded by immunohistochemical staining of α-smooth muscle actin (α-SMA) protein. The relations of PSC activity with CR-POPF and the pancreatic texture, as well as the relations of other relevant clinicopathologic factors with CR-POPF were analyzed. The efficiency of PSC activity in predicting CR-POPF was determined by ROC analysis.
Results: In the 101 patients, CR-POPF occurred in 41 cases (40.6%). Results of analysis showed that the incidence of CR-POPF was decreased progressively with the increase of the grade of PSC activity, and the distributions of PSC activity grades were significantly different among different pancreatic textures (both P<0.001). Results of correlation analysis showed that the degree of PSC activity was positively correlated with the hardness of pancreatic texture (r=0.456, P<0.001), while was negatively correlated with the incidence of CR-POPF (r=–0.539, P<0.001). Results of univariate analysis showed that pancreatic texture, tumor pathology, PSC activity grade, preoperative body mass index, pancreatic duct diameter, preoperative total bilirubin, drainage fluid amylase on postoperative day 1 were significantly associated with the occurrence of CR-POPF (all P<0.05), and the results of multivariate Logistic regression analysis showed that the PSC activity (OR=0.24, 95% CI=0.10–0.56, P<0.001) and preoperative total bilirubin (OR=1.01, 95% CI=1.00–1.01, P=0.008) were the independent risk factors for CR-POPF. Results of ROC analysis showed that the AUC of the degree of PSC activity for predicting CR-POPF was 0.795 (95% CI=0.708–0.881), with a sensitivity of 63.3% and a specificity of 87.8%.
Conclusion: The degree of PSC activity can objectively and accurately reflect the hardness of the pancreatic texture. It is an effective index for predicting the CR-POPF following PD, and has certain clinical application value.