Construction and validation of a nomogram prediction model for early recurrence of patients undergoing radical pancreaticoduodenectomy for pancreatic ductal adenocarcinoma / 中华肝胆外科杂志

Objective:To study the risk factors for early recurrence of patients undergoing radical pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) and construct a normogram model.Methods:Patients undergoing open radical PD for PDAC at Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from January 2014 to December 2021 were retrospectively screened. A total of 213 patients were enrolled, including 145 males and 68 females, aged (58.4±9.8) years. Patients were divided into the early recurrence group ( n=59, recurrence within 6 months after surgery) and a control group ( n=154, no recurrence within 6 months after surgery). Using minimum absolute value convergence and selection operator regression (LASSO) and multi-factor logistic regression analysis, we screened out the best predictor of early recurrence after PD for PDAC, and then established a nomogram model. The effectiveness of the model was validated by receiver operating characteristic (ROC) curve, calibration curves, and decision analysis curves. Results:Multivariate logistic regression analysis showed that patients with obstructive jaundice, vascular invasion, massive intraoperative bleeding, high-risk tumors (poorly differentiated or undifferentiated), high carbohydrate antigen 19-9 to total bilirubin ratio, and high fibrinogen and neutrophil to lymphocyte ratio scores had a higher risk of early postoperative recurrence. Based on the indexes above, a nomogram prediction model was constructed. The area under the ROC curve was 0.797 (95% CI: 0.726-0.854). Validation of the calibration curve exhibited good concordance between the predicted probability and ideal probability, decision curve analysis showed that the net benefits of the groupings established according to the model were all greater than 0 within the high risk threshold of 0.08 to 1.00. Conclusion:The nomogram for predicting early recurrence after PD for PDAC has a good efficiency, which could be helpful to screen out the high-risk patients for adjuvant or neoadjuvant therapy.

Research progress of stroma-targeted therapies for pancreatic ductal adenocarcinoma / 中华肝胆外科杂志

Desmoplastic stroma of pancreatic ductal adenocarcinoma plays an important role in tumor progression and treatment resistance. Stroma-targeted therapies are therefore promising for clinical application and extensive related researches are undergoing. In this article, recent advances in stromal targeting strategies were reviewed from three perspectives: cancer-associated fibroblasts, extracellular matrix and angiogenesis, and an outlook for the future of this strategy was also provided.

Advances in clinical assessment and decision-making of intraductal papillary mucinous neoplasm in pancreas / 中华肝胆外科杂志

Intraductal papillary mucinous neoplasm (IPMN) is one of the precancerous lesions of the pancreas. Currently there is controversial over the management and follow-up strategy of IPMN, including the timing of surgery. The core problem lies in the accurate preoperative assessment of the nature of the lesions and the risk of malignant transformation. Cumulation of high-quality evidence and development of efficient evaluation methods are vital for the establishment of standardized decision-making system and the improvement of clinical benefits to patients. This review aims to summarize the consensus and controversies on surgical evaluation standards in the latest guidelines and representative literatures, and to look forward to the development direction of IPMN diagnosis and treatment decisions in combination with the progress of related evaluation techniques.

Construction and validation of the preoperative nomogram diagnosis model for pancreatic head cancer and distal cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the differences in preoperative examination indexes between pancreatic head cancer and distal bile duct cancer, and to establish a preliminary prediction model to provide reference for clinical decision-making.Methods:Retrospective analysis was conducted on 243 consecutive patients who underwent open radical pancreaticoduodenectomy from January 1, 2015 to December 31, 2019 at the Chinese PLA General Hospital. There were 177 males and 66 females, aged (58.9±8.9) years old. Based on postoperative pathological results, these 243 patients were divided into the pancreatic head cancer group ( n=113) and the distal bile duct cancer group ( n=130). The clinical data of the two groups were collected. Minimum absolute value convergence and selection operator regression were used to screen the best predictors of pancreatic head cancer. The rms package was used to construct the nomogram model, and k-fold cross was used for internal validation. Results:Seven best predictive indexes are selected: age, rate of weight loss, main pancreatic duct diameter, neutrophil/lymphocyte, DTR (DBil/TBil), carcinoembryonic antigen and CA125. Based on these indexes, a nomogram prediction model was constructed with the C-index of 0.868 after k-fold cross-validation, indicating that discrimination of the model to be acceptable. Validation using calibration curve exhibited good concordance between the predicted probability with the ideal probability ( P=0.728). Conclusion:The nomogram prediction model established in this study effectively predicted patients with pancreatic head cancer, and helped preoperatively to differentiate pancreatic head cancer from distal cholangiocarcinoma.

Construction and evaluation of a nomogram in predicting overall survival in patients with pancreatic ductal adenocarcinoma after R 0 radical pancreaticoduodenectomy / 中华肝胆外科杂志

Objective:To construct a predictive nomogram on postoperative overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) after R 0 radical pancreaticoduodenectomy, and to evaluate its performance. Methods:The clinicopathological data of patients who underwent radical pancreaticoduodenectomy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from January 2014 to December 2019 for pathologically diagnosed PDAC were retrospectively collected and analyzed. There were 119 patients, with 85 males and 34 females, aged (58±11) years. Using multivariate Cox regression analysis (stepwise regression), a prediction nomogram was constructed. Concordance index (C-index), calibration curve, and time-dependent receiver operating characteristic (ROC) curve were applied to evaluate the predictive performance.Results:The 1-, 2-, and 3-year cumulative survival rates of these 119 patients were 67.2%, 35.0%, and 24.8%, respectively. High-grade tumors (poorly differentiated and undifferentiated), vascular carcinoma embolus, systemic immune inflammatory index <279.4×10 9/L, prognostic nutritional index <40.5, alanine aminotransferase-to-aspartate aminotransferase ratio>1.1, total bilirubin>258.5 μmol/L and plasma fibrinogen>3.43 g/L were independent risk factors for poor OS for PDAC patients after radical pancreaticoduodenectomy (all P<0.05). These indicators, together with age >63 years, constituted the regression formula for prediction with a C-index=0.74. The areas under the curve of ROC for the nomogram on predicting survival were 0.795, 0.803, and 0.836 at 1, 2, and 3-year respectively, and only slight deviations were observed on the calibration curves from the standard 45° line, suggesting that the survival prediction of the model in this dataset fitted well with the actual survival status. Conclusion:The predictive nomogram on OS in patients after R 0 radical pancreaticoduodenectomy based on the clinicopathological characteristics of PDAC was internally validated to have a good predictive performance on OS. The nomogram can help to optimize prognostic risk stratification and treatment decisions for this subgroup of patients. This prediction model needs to be further verified and improved by using large-scale cohort studies.

Risk factors of pathological positive resection margins in patients undergoing curative-intent resection for advanced hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the risk factors of positive surgical margins in patients with advanced hilar cholangiocarcinoma (HCCA) undergoing curative-intent resection with the aim to provide references for clinical decision-making.Methods:The clinical pathological data of 126 patients with advanced HCCA who underwent curative-intent resection at the Chinese PLA General Hospital from January 2011 to December 2014 was retrospective analyzed. There were 78 males and 48 females, with an average age of 55 years. The patients were divided into two groups: the resection margin positive group (positive for residual tumor at any surgical margin, n=29) and the negative resection margin group ( n=97). Multivariate logistic regression analysis, in reference to the results of univariate analysis, was applied to the relevant variables to study independent risk factors of positive resection margin. Receiver operating characteristic (ROC) curves were drawn to evaluate the independent and joint predictive values of the relevant indicators. Results:Univariate analysis showed vascular involvement, tumor diameter volume ≥20.94 cm 3, plasma fibrinogen ≥3.36 g/L, and DRR≤0.61 were associated with positive resection margins (all P<0.05). A history of cholecystectomy was potentially associated with positive resection margins ( P<0.1). These variables were included in the multivariate logistic regression analysis which showed vascular involvement ( OR=4.134, 95% CI: 1.545-11.060, P=0.005), tumor size ≥ 20.94 cm 3 ( OR=2.926, 95% CI: 1.107-7.733, P=0.030) and DRR≤0.61 ( OR=3.170, 95% CI: 1.126-8.928, P=0.029) were independent risk factors of positive margins after curative resection in patients with advanced HCCA. ROC curve analysis was used to evaluate the impact of the combination of the above variables in predicting positive surgical margins. Sensitivity and specificity were calculated to be 86.2% and 65.7% respectively, and the area under the curve was 0.771. Conclusion:Vascular involvement, tumor size ≥20.94 cm 3 and DRR≤0.61 were independent risk factors of positive surfical margins in patients with advanced HCCA undergoing curative-intent resection. The combination of the above predictive indicators provided some references for treatment decisions.

Research progress of PD-1 antibody therapy and related biomarkers in biliary tract cancers / 中华肝胆外科杂志

Biliary tract cancer is characterized by high heterogeneous, rare and refractory malignancy. Since patients are often diagnosed at late stage, the radical resection rate is low, and the effect of traditional adjuvant therapy is limited, therefore the prognosis of patients is poor. Recently Immunotherapy has opened up a new field for tumor therapy. Porgrammed death-1 (PD-1) antibody therapy has a great clinical application prospects. The efficacy of related therapies in biliary tract tumors is being evaluated under a number of clinical trials. One of the main challenges is to identify the biomarkers that can predict the response and prognosis of PD-1 antibody therapy. This article aims to summarize the research progress of PD-1 antibody therapy and related biomarkers such as PD-L1, tumor mutational burden, DNA damage repair in biliary tract cancers, and to prospect the future research direction.