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.

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.

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.

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.

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.

Objective:To assess the predictive value of aspartate aminotransferase-to-alanine amino-transferase ratio (DRR) on overall survival of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent radical pancreaticoduodenectomy.Methods:A retrospective analysis was performed on the clinical data of 137 patients who underwent radical pancreaticoduodenectomy and were diagnosed with PDAC postoperatively at the Chinese PLA General Hospital from January 2015 to December 2020. There were 97 male and 40 female patients, with an average age of (58±10) years old. The patients were grouped according to the optimal survival risk cutoff value of DRR, and the differences in key clinical and pathological indicators between the groups were compared. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison of survival rates. Multivariate Cox analysis was performed to evaluate the prognostic factors affecting survival.Results:The 137 PDAC patients were divided into two groups based on the optimal cutoff value of DRR, namely 1.1: DRR≥1.1 was defined as the high-DRR group ( n=29), and DRR<1.1 was defined as the low-DRR group ( n=108). The cumulative survival rate of the low-DRR group was better than that of the high-DRR group, and the difference was statistically significant ( P=0.003). The results of the multivariate Cox regression analysis showed that DRR≥1.1 ( HR=2.485, 95% CI: 1.449-4.261, P=0.001), preoperative biliary drainage ( HR=1.845, 95% CI: 1.030-3.306, P=0.039), lymph node metastasis N2 stage ( HR=2.240, 95% CI: 1.123-4.470, P=0.022), high tumor differentiation ( HR=2.001, 95% CI: 1.279-3.129, P=0.002), and intravascular cancer emboli ( HR=2.240, 95% CI: 1.123-4.470, P=0.022) were risk factors for poor overall survival in PDAC patients who underwent radical pancreaticoduodenectomy. Conclusion:DRR has predictive value for overall survival after surgery in PDAC patients undergoing radical pancreatoduodenectomy. A DRR of 1.1 or greater is a risk factor for poor overall survival after surgery in PDAC patients.

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.

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.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.