Objective ·To modify previous clinically relevant post-operative pancreatic fistula (CR-POPF) risk evaluation models with quantitative evaluation of pancreatic tissue stiffness by ultrasound shear wave elastography (SWE). Methods ·In this prospective study, the patients who were diagnosed as having pancreatic tumors and scheduled to undergo pancreatectomy at Zhongshan Hospital, Fudan University were initially enrolled, whose clinical information was collected. Virtual touch tissue imaging and quantification technology (VTIQ) assessment was applied to the patients within one week before the surgery to measure the shear wave velocity (SWV) of pancreatic lesions and the normal parenchyma of pancreatic body in the superficial layer of the portal vein. During the surgery, the surgeons qualitatively evaluated the stiffness of pancreases via direct palpation and divided them into soft pancreases and medium-hard pancreases. During the 3-week follow-up period after pancreatectomy, CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula (ISGPF) standard. Peri-operative risk factors of CR-POPF were analyzed by univariate and multivariate Logistic regression to build the prediction model. Evaluation and comparison of diagnostic efficacy and clinical benefits among different models were then performed via receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results ·From September 2021 to March 2022, 100 patients were enrolled in this study, including 33 patients (33.0%) who received pancreaticoduodenectomy (PD) and 67 patients (67.0%) who received distal pancreatectomy. CR-POPF was diagnosed in 35 patients (35.0%) during the 3-week post-pancreatectomy follow-up. Multivariate Logistic regression analysis revealed that the SWV value of the body part of pancreatic parenchyma in the superficial layer of the portal vein [lgOR=-2.934 (95%CI -4.387?-1.479), P=0.000] and the presence of a non-dilated main pancreatic duct (≤3 mm) [lgOR=0.805 (95%CI 0.274?1.335), P=0.003] were independent risk factors that significantly correlated with the occurrence of CR-POPF after pancreatectomy. The modified model based on the SWE parameter achieved the area under the ROC curve of 0.842, with the sensitivity, the specificity, the positive predictive value, the negative predictive value and the likelihood ratio of 85.7%, 64.6%, 70.5%, 81.8% and 2.422 in predicting CR-POPF. DCA revealed a better clinical benefit of the modified model compared to the previous prediction models [fistula risk score (FRS) and alternative fistula risk score (a-FRS)]. Conclusion ·The modified model based on the SWE parameter and identified clinical risk factors can make non-invasive, quantitative and objective evaluation of CR-POPF risk before pancreatectomy, and provide sufficient diagnostic efficacy and clinical benefits.