Research advances in the diagnosis and treatment of benign gallbladder disease / 中华肝胆外科杂志

Benign gallbladder diseases are common in general surgery practice, and laparoscopic cholecystectomy (LC) has become the standard treatment for these conditions. With the widespread adoption of LC and the improved understanding of gallbladder disease, it is necessary to re-evaluate the diagnosis and treatment of benign gallbladder disease. Based on the latest expert consensus on the diagnosis and treatment of benign gallbladder disease, this review aims to provide an overview of the diagnostic and treatment strategies for benign gallbladder diseases. Specifically, it focuses on enhancing our understanding of the role of benign gallbladder diseases in the development of gallbladder cancer, the impact of congenital biliary anomalies on the diagnostic and treatment processes of benign gallbladder diseases, and the significance of the preoperative examinations.

Prognostic analysis and predictive model construction of textbook outcome after gallbladder carcinoma surgery / 中华肝胆外科杂志

Objective:To analyze independent influencing factors of surgical textbook outcome (TO) in patients with gallbladder carcinoma, and to establish a nomogram for predicting TO and evaluated the predictive ability.Methods:Patients with gallbladder carcinoma who underwent surgery in Department of Hepatobiliary and Pancreatic Surgery at Dongfang Hospital Affiliated to Shanghai Tongji University and Department of Biliary Tract Surgery Ⅰ, Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) from January 2013 to December 2018 were included and the clinical features were retrospectively analyzed. A total of 232 patients were included, including 114 males and 118 females, aged (61.0±9.8) years. According to whether TO reached or not, they were divided into TO group ( n=86) and non-TO group ( n=146). Univariate and multivariate logistic regression were used to analyze the independent influencing factors of TO. The predictive nomogram model of TO was constructed. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive ability of the model, and the consistency of the predictive model was evaluated by the consistency curve graph and the Hosmer-Lemeshow test. Results:The 1-year and 3-years cumulative survival rates of patients with gallbladder carcinoma in the TO group (86.0% and 62.8%) were better than those in the non-TO group (46.6% and 27.3%), and the difference was statistically significant (χ 2=60.74, P<0.001). In multivariate analysis, higher T stage ( OR=0.16, 95% CI: 0.03-0.79, P<0.001) and cervical gallbladder cancer ( OR=0.14, 95% CI: 0.02-0.94, P=0.004) had the greatest negative association with a TO, and the higher the degree of tumor differentiation ( OR=7.08, 95% CI: 1.34-37.56, P=0.001), the easier it is to achieve TO. The ROC curve showed that the area under the curve of the predictive model was 0.84 (95% CI: 0.79-0.90), suggesting that the model had good predictive performance. A nomogram to assess the probability of TO was developed and had good accuracy in both the consistency curve and Hosmer-Lemeshow test (χ 2=5.77, P=0.673). Conclusion:Tumor T stage, tumor differentiation degree and tumor location are independent influencing factors for achieving TO in patients with gallbladder carcinoma after surgery. The nomogram model constructed according to the above conclusions could accurately predict the probability of reaching TO.

Risk factors in predicting lymph node metastases in intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the risk factors of lymph node metastases in patients with intrahepatic cholangiocarcinoma (ICC) and to establish a risk prediction model of lymph node metastases in ICC.Methods:The clinicopathological data of 587 ICC patients who underwent radical hepatectomy and lymph node dissection at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) from January 2007 to December 2011 were retrospectively analyzed. There were 395 males and 192 females with ages which ranged from 20 to 82 (54.7±10.8) years. Independent risk factors of lymph node metastases were studied using univariate and multivariate logistic regression analysis, and a risk prediction model was established. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of this model.Results:Of 587 patients, 158 (26.9%) had lymph node metastases. Multivariate logistic regression analysis showed that platelet count >300×10 9/L ( OR=1.985, 95% CI: 1.030-3.824, P=0.041), carbohydrate antigen 19-9 >37 U/ml ( OR=2.978, 95% CI: 1.994-4.448, P<0.001), tumor situated in left hemiliver ( OR=1.579, 95% CI: 1.065-2.341, P=0.023), multiple tumors ( OR=1.846, 95% CI: 1.225-2.783, P=0.003), and absence of cirrhosis ( OR=2.125, 95% CI: 1.192-3.783, P=0.011) were independent risk factors for lymph node metastases in ICC. The area under the ROC curve was 0.714, with a cutoff value of 0.215, and the sensitivity and specificity being 75.9% and 58.3%, respectively. Conclusions:The risk prediction model of ICC lymph node metastases was established using readily available clinical data obtained before operation. This model has good predictive values and can provide a reference for treatment decision on patients with ICC.

Influence of different options of preoperative biliary drainage on perioperative complications of patients with periampullary carcinoma undergoing pancreaticoduodenectomy / 中华肝胆外科杂志

Objective:To evaluate the effect of different options of preoperative biliary drainage (PBD) on perioperative complications of patients undergoing pancreaticoduodenectomy (PD).Methods:The clinical data of patients undergoing PD for periampullary carcinoma from January 2016 to November 2021 at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) were retrospectively analyzed. The 303 patients including 199 males and 104 females, aged (64.2±8.8) years. According to PBD, the patients were divided into two groups: percutaneous transhepatic biliary drainage (PTBD) group ( n=228) and endoscopic retrograde cholangiopancreatography (ERCP) group ( n=75). PBD operation-related complications (including bleeding, biliary leakage, etc.), postoperative complications of PD (including pancreatic fistula, biliary leakage, surgical site infection, etc.) and perioperative complications (PBD operation-related complications + postoperative complications of PD) were compared between the two groups. Univariate and multivariate logistic regression analysis were used to analyze factors influencing perioperative complications of PD. Results:The incidence of PBD operation-related complications in PTBD group was 10.1% (23/228), lower than that in ERCP group 25.3%(19/228), and the difference was statistically significant (χ 2=10.99, P=0.001). The incidence of postoperative complications of PD in PTBD group was 38.2%(87/228), lower than that in ERCP group 69.3%(52/75), the difference was statistically significant (χ 2=22.09, P<0.001). The incidence of total perioperative complications in PTBD group was 44.3% (101/228), lower than that in ERCP group 73.3%(55/75), the difference was statistically significant (χ 2=19.05, P<0.001). Multivariate logistic regression analysis showed that patients with periampullary carcinoma undergoing ERCP biliary drainage and PD had increased risk of surgical site infection ( OR=2.86, 95% CI: 1.59-5.16, P<0.001) and pancreatic fistula ( OR=3.06, 95% CI: 1.21-7.74, P=0.018). Conclusion:ERCP biliary drainage is a risk factor for postoperative pancreatic fistula and surgical site infection in patients with periampullary carcinoma undergoing PD. PTBD should be recommended as the first choice for the patients underwent PD.

Whole disease cycle management of hilar cholangiocarcinoma / 中华肝胆外科杂志

Hilar cholangiocarcinoma is the most common malignant tumor of the biliary tract, the survival rate is poor due to the difficulty of early diagnosis and surgery. Progress have been made on hilar cholangiocarcinoma treatment during recent years, but it is still challenging to make a breakthrough. The whole disease cycle management is of great significance to improve the prognosis of patients with hilar cholangiocarcinoma. The whole disease cycle management refers to the whole-process scientific management including disease diagnosis, preoperative evaluation and preparation, surgical plan formulation and implementation, preoperative and postoperative adjuvant treatment and follow-up. This article summarized the domestic and foreign progress on the management of hilar cholangiocarcinoma in all stages of the whole disease cycle and shared the author's team's experience in the diagnosis and treatment of hilar cholangiocarcinoma.

Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases / 中华消化外科杂志

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.

Etiological characteristics of infection after percutaneous biliary drainage or stent implantation for malignant biliary obstruction / 临床肝胆病杂志

Objective To investigate the etiological characteristics of infection after percutaneous biliary drainage or stent implantation in patients with malignant biliary obstruction (MBO). Methods Clinical data were collected from MBO patients who underwent interventional therapy in Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, from January 2016 to December 2020 and had or were suspected of biliary tract infection, with samples submitted for bile culture and/or simultaneous blood culture. Analysis was performed for the aspects of positive rate of culture, flora distribution, consistency between blood culture and bile culture, and drug resistance rate of major pathogenic bacteria. Results A total of 219 patients were enrolled, among whom 105(47.95%) were positive for bile culture, and the composition ratios of Gram-negative bacteria, Gram-positive bacteria, and fungi were 64.89%, 28.24%, and 6.87%, respectively. A total of 69 patients had samples submitted for blood culture during the same period of time, among whom 33(47.82%) had positive results. Positive results of both bile culture and blood culture were observed in 25 patients, and consistency analysis showed that the patients with complete consistency, partial consistency, and complete inconsistency accounted for 36%(9/25), 20%(5/25), and 44%(11/25), respectively. Common Gram-negative bacteria were Escherichia coli , Klebsiella pneumoniae , and Enterobacter cloacae , with a relatively low level of drug resistance to antibiotics including cefoperazone/sulbactam, amikacin, and imipenem. Common Gram-positive bacteria were Enterococcus faecium and Enterococcus faecalis , with a relatively low level(< 15%) of drug resistance to antibiotics including vancomycin, linezolid, and teicoplanin. Conclusion Common pathogens of infection after percutaneous biliary drainage or stent implantation in MBO patients include Escherichia coli , Klebsiella pneumoniae , Enterococcus, and Enterobacter cloacae . There is a relatively low level of consistency between blood culture and bile culture, and thus samples should be submitted for both tests.

Incidence and risk factors analysis of colorectal adenomatous polyps in recipients after liver transplantation / 器官移植

Objective To analyze the incidence and risk factors of colorectal adenomatous polyps (CAP) in recipients after liver transplantation. Methods Seventy-seven liver transplant recipients and 231 individuals undergoing colonoscopy during physical examination were recruited in this study. The incidence of CAP and pathological examination results were analyzed. Clinical data of liver transplant recipients were collected. According to the incidence of CAP, liver transplant recipients were divided into the CAP group (n=28) and non-CAP group (n=49). The risk factors of CAP after liver transplantation were identified. Results The 5-year cumulative incidence rates of colorectal polyps in liver transplant recipients and physical examination individuals were 43% and 34%, and 29% and 23% for the 5-year cumulative incidence rates of CAP, with no significant differences (both P > 0.05). Among all liver transplant recipients, 65 polyps were detected. The quantity of polyps in 1 case was excessively high and not counted. Multiple polyps were identified in certain recipients. Five polyps were not prepared for pathological examination due to small size. Pathological examination of 60 polyps demonstrated 25 inflammatory polyps, 33 CAP (8 complicated with low-grade intraepithelial neoplasia and 3 complicated with high-grade intraepithelial neoplasia), and 2 well-differentiated adenocarcinoma. Cox model analysis prompted that use of ciclosporine after liver transplantation was an independent risk factor for CAP in the recipients. Conclusions The risk of CAP is slightly elevated after liver transplantation. Postoperative use of ciclosporine is an independent risk factor for CAP in recipients after liver transplantation. Colonoscopy should be emphasized in the recipients after liver transplantation.

Key points of surgical treatment of congenital choledochal cysts and the clinical significance of the " three regions and five types" classification system / 中华肝胆外科杂志

Congenital bile duct cysts, which is a kind of malformation of bile duct, will lead to the inflammation in the bile duct system for a long time. Therefore, patients with cholelithiasis and cyst canceration have a risk. Surgical operation is the only treatment option for the congenital bile duct cysts patients. Resection of the cysts and complete " biliary-pancreatic duct shunt" are the key points of the standardized treatment of congenital bile duct cysts. The non-standard surgical treatment will bring the postoperative complications such as the stricture of choledochojejunostomy, the remnant cysts and even the canceration of cysts, which will seriously affect the quality of life and threaten the health of patients. Based on the retrospective study of congenital bile duct cysts patients in Eastern Hepatobiliary Hospital, the author proposed a new classification system according to the pathological and anatomical characteristics of congenital bile duct cysts. The congenital bile duct cysts can be divided into three regions and five types, i. e. localized type and diffuse type of extrahepatic bile duct cysts of hilar, trunk and terminal type; central type; and intrahepatic bile duct cysts of limited and diffuse type. It is our hope that this typing system will accurately guide the design and implementation of surgical treatment plans for congenital bile duct cysts and reduce the risk of long-term postoperative complications for patients.

Progress of immunotherapy of cholangiocarcinoma / 中华肝胆外科杂志

Cholangiocarcinoma (CCA) is a group of solid tumors with high malignant degree and poor prognosis. Surgical resection has still been the main therapy options. Targeting therapy and immunotherapy are the main anti-tumor methods that have been paid more and more attention in recent years, especially immunotherapy. The tumor microenvironment of CCA is complex, which encompasses not only interstitial and endothelial cells, but also a large number of immune cells. In addition, the innate and adaptive immune systems also play a role. This article summarizes the immune-related studies of cholangiocarcinoma and the latest clinical trials of immunotherapy.

Controversies and Considerations on Surgical Treatment of Gallbladder Cancer / 肿瘤防治研究

Gallbladder cancer is a high malignancy which is predisposed to invade adjacent organs and have lymph node metastasis. Gallbladder cancer is not sensitive to radiotherapy or chemotherapy with the worst prognosis among biliary tract cancers. At present, radical resection is the only possible method to cure gallbladder cancer. However, there are still many controversies about the surgical strategies, the extent of liver resection and lymph node dissection, and the treatment of incidental gallbladder cancer. In addition, under the background of the great success of immunotherapy and targeted therapy in a variety of solid tumors, it is also a question worthy of further considerations that whether the status of surgery in the treatment of advanced gallbladder cancer will be changed in the near future.

Characteristics of immune microenvironment and progress of immune checkpoint inhibitors to cholangiocarcinoma treatment / 中华肝胆外科杂志

Cholangiocarcinoma is a highly malignant disease with low surgical resection rate. It’s resistant to chemoradiotherapy and the prognosis of cholangiocarcinoma is poor. Although immune checkpoint inhibitors (ICIs) have achieved great success in tumor therapy in recent years, patients with cholangiocarcinoma have a poor response to immunotherapy, because of the complexity and diversity of immune microenvironment. Therefore, understanding the composition and characteristics of the immune microenvironment of cholangiocarcinoma, regulating targets in immune microenvironment, and adopting ICIs combined therapy, is important for immunotherapy for cholangiocarcinoma.

Literature analysis report of de novo malignant tumors of digestive system after liver transplantation in China / 器官移植

Objective To investigate the incidence of de novo malignant tumors of the digestive system after liver transplantation (LT) in China. Methods Relevant literature review was performed from Wanfang data, China National Knowledge Infrastructure (CNKI) and Chongqing VIP. The retrieval time started from the establishment of each database to May 9, 2019. The Chinese search terms were liver transplantation+ postoperative/de novo+ malignant tumor/cancer. The age distribution, sex composition, time of diagnosis, involved organs, treatment and clinical prognosis of recipients with de novo malignant tumors of the digestive system after LT in China were retrospectively analyzed. Results After literature screening, 16 articles were eventually selected including 47 cases of de novo malignant tumors of the digestive system after LT. A majority of them were male recipients. The age of the recipients was 51 (23-65) years old, most of them were middle age (45-59 years old). The average time of diagnosis of de novo malignant tumors of the digestive system after operation was 43 (2-156) months, with the highest number of cases within postoperative 1-3 years. Colon and stomach were the most common tumor sites. Surgery combined with radiotherapy and chemotherapy remained the main treatment option. However, the overall clinical prognosis of patients with de novo malignant tumors of the digestive system after LT was poor with a mortality rate of 51%. Conclusions In China, colon cancer and gastric cancer are the main de novo malignant tumors of the digestive system after LT. The overall clinical prognosis of patients with de novo malignant tumors of the digestive system is poor. Sufficient attention should be paid to postoperative monitoring and prevention.

The expression and prognostic significance of Aurora Kinase A in hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To explore the expression of Aurora Kinase A (AURKA) in hepatocellular carcinoma (HCC) and its prognostic value.Methods:mRNA expression profiles and clinical data of HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. Expression of AURKA mRNA in HCC patients of TCGA database from normal liver tissue and all tumor tissues, normal tissues adjacent to cancer and matched tumor tissues were analyzed, and then expression of AURKA to was investigated in HCC tissues and normal liver tissues in the Human Protein Atlas (HPA) database. According to the TNM stage information of HCC patients in TCGA database, expression of AURKA in different stages was analyzed. Kaplan-Meier method was used to analyze whether the high and low expression of AURKA in HCC patients of TCGA database (with the median as the cut-off value) was significantly related to the length of survival. The RNA-seq expression profile data of HCC patients in the public resource platform of the Kaplan-Meier Plotter website was used for external verification. Cox univariate and multivariate analysis were performed on the age, sex, degree of differentiation, TNM stage, and AURKA mRNA expression of TCGA database patients.Results:374 cases of HCC tumor tissues and 50 cases of adjacent normal liver tissues in the TCGA database were included. All HCC tumor tissues in the TCGA database compared with the paired adjacent tissues mRNA level of AURKA was significantly increased, and the protein level was also increased, the difference was statistically significant ( P<0.05); With the tumor TNM stage increase of AURKA mRNA expression showed a gradual upward trend, and the difference was statistically significant ( P<0.05); in the TCGA database HCC cohort, high expression of AURKA mRNA was associated with poor HCC prognosis, and was obtained in Kaplan Meier Plotter database. The difference was statistically significant ( P<0.05); Cox multivariate regression analysis showed that TNM stage ( HR=1.69, 95% CI: 1.37-2.10) and AURKA mRNA expression level ( HR=1.03, 95% CI: 1.01-1.10) are the independent prognostic factors of HCC patients. Conclusions:AURKA is highly expressed in HCC, which is associated with the poor prognosis of HCC. AURKA is an independent prognostic factor of HCC.

A comparative study on preoperative portal vein embolization using tris-acryl gelatin microspheres versus coils / 中华肝胆外科杂志

Objective:To compare preoperative portal vein embolization (PVE) using tris-acryl gelatin microspheres (TAGM) versus coils.Methods:From March 2016 to June 2018, 21 consecutive patients with a future liver remnant (FLR) ratio of less than 45% before planned major hepatectomy for malignant or benign liver diseases were enrolled from the First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital into this study. The patients were divided to receive portal vein embolization (PVE) using TAGM distally and coils proximally (the TC group) and PVE using multiple coils (the CC group). Post-PVE complications, liver function, routine blood tests; FLR hyperplasia, types of liver resection, operation time, intraoperative blood loss, and postoperative complications were compared between the two groups.Results:Eight patients were included in the TC group. There were 4 males and 4 females, with a mean age of (55.3±7.7) years. Of 13 patients included into the CC group, there were 11 males and 2 females, with a mean age of (52.6±11.3) years. There were no significant differences in sex, age, types of hepatic diseases, volume of FLR, ratio of FLR, ratio of standard FLR, types of surgery, operation duration, blood loss, major complications, and liver failure rates between the two groups. All patients in the two groups had successful PVE. The TC group developed effective growth of volume of FLR with one patient who failed to undergo surgery because of tumor progression. In the CC group, four patients failed to undergo liver resection: one patient developed thrombosis of the left branch and main trunk of portal vein; tumor progression occurred in one patient and two patients had insufficient FLR growth. Compared with the CC group, the TC group had a significantly higher volume of FLR hyperplasia [(9.0±2.8) % vs. (5.2±3.8) %, P<0.05], and a faster but insignificant increase in proliferation rate [(11.4±7.1) ml/d vs. (6.9±5.2) ml/d, P>0.05], a greater but insignificant increase in percentage of proliferation [(33.6±20.1) % vs. (20.9±15.1) %, P>0.05]. Conclusions:This study showed that PVE with TAGM plus coils is safe and effective. It induced a better degree of hypertrophy of FLR compared to PVE using multiple coils.

Ponatinib inhibits growth of patient-derived xenograft of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein in nude mice / 南方医科大学学报

OBJECTIVE@#To investigate the antitumor effect of ponatinib on the growth of cholangiocarcinoma xenograft derived from a clinical patient in a mouse model expressing FGFR2-CCDC6 fusion protein.@*METHODS@#Lung metastatic tumor tissue was collected from a patient with advanced intrahepatic cholangiocarcinoma and implanted subcutaneously a NOD/SCID/ Il2rg-knockout (NSG) mouse. The tumor tissues were harvested and transplanted in nude mice to establish mouse models bearing patient-derived xenograft (PDX) of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein. The PDX mouse models were divided into 4 groups for treatment with citrate buffer (control group), intragastric administration of 20 mg/kg ponatinib dissolved in citrate buffer (ponatinib group), weekly intraperitoneal injections of 50 mg/kg gemcitabine and 2.5 mg/ kg cisplatin (gemcitabine group), or ponatinib combined with gemcitabine and cisplatin at the same doses (10 mice in each group, and 9 mice were evaluated in ponatinib group). The expressions of p-FGFR, p-FRS2, p-AKT, p-ERK, CD31, and Ki-67 in the xenografts were evaluated with immunohistochemistry, and cell apoptosis was analyzed with cleaved caspase-3 (CC3) staining and TUNEL staining. Western blotting was used to detect the expressions of FGFR2, p-FGFR, AKT, p-AKT, ERK, p-ERK, FRS2 and p-FRS2 in the tumor tissues.@*RESULTS@#Compared with those in the control group, the mice in ponatinib group showed a significantly reduced tumor volume (@*CONCLUSIONS@#Ponatinib can regulate FGFR signaling to inhibit the proliferation and induce apoptosis of tumor cells in mice bearing patient-derived cholangiocarcinoma xenograft with FGFR2 fusion. FGFR inhibitor can serve as a treatment option for patients with cholangiocarcinoma with FGFR2 fusion.

Magnetic resonance cholangiopancreatography digital quantitative diagnosis in the differential diagnosis of choledochal cyst type Ic / 中华肝胆外科杂志

Objective@#To study the use of MRCP digital quantitative diagnosis in the differential diagnosis of choledochal cyst type Ic.@*Methods@#The clinical data of 41 patients with choledochal cyst type Ic, 47 patients with distal choledochal obstruction and 43 patients with simple gallbladder stones or polyps who were treated at the Eastern Hepatobiliary Surgery Hospital, PLA Naval Medical University from January 2010 to June 2016 were retrospectively analyzed. The diameters of the common bile duct, the left and the right hepatic ducts were measured and compared.@*Results@#The maximum diameter of the left hepatic duct (LHD), right hepatic duct (RHD) and common bile duct (CBD) were significantly different (all P<0.05) in patients with choledochal cyst type Ic compared to patients with distal choledochal obstruction. The CBD/LHD ratio and CBD/RHD ratio were significantly larger (P<0.05). For patients with choledochal cyst type Ic, when compared with patients with simple gallbladder stones or polyps, the maximum diameter of CBD was significantly larger (P<0.05), but the maximum diameters of LHD and RHD were not significantly different (both P>0.05), while the ratios of CBD/LHD and CBD/RHD were significantly larger (P<0.05). For patients with choledochal cyst type Ic, when compared with patients with simple gallbladder stones or polyps, the maximum diameter of CBD was significantly larger (P<0.05), the maximum diameter of LHD and RHD was also significantly larger (P<0.05), while the ratios of CBD/LHD and CBD/RHD were not significantly different (P>0.05). The proportion of pancreaticobiliary maljunction (PBM) in patients with type Ic choledochal cyst was significantly higher than patients with distal choledochal obstruction and simple gallstone or polyp (P<0.05).@*Conclusions@#For patients with choledochal cyst type Ic, their CBD shows obvious dilation, while there is no obvious dilation in LHD and RHD. It is helpful to conduct differential diagnosis of choledochal cyst type Ic by the use of MRCP to observe the presence of PBM and to quantitatively compare the CBD/LHD and CBD/RHD ratios.

Magnetic resonance cholangiopancreatography digital quantitative diagnosis in the differential diagnosis of choledochal cyst type Ic / 中华肝胆外科杂志

0bjective To study the use of MRCP digital quantitative diagnosis in the differential diagnosis of choledochal cyst type Ic.Methods The clinical data of 41 patients with choledochal cyst type Ic,47 patients with distal choledochal obstruction and 43 patients with simple gallbladder stones or polyps who were treated at the Eastern Hepatobiliary Surgery Hospital.PLA Naval Medical University from January 2010 to June 2016 were retrospectively analyzed.The diameters of the common bile duct,the left and the fight hepatic ducts were measured and compared.Results The maximum diameter of the left hepatic duct(LHD),right hepatic duct(RHD)and common bile duct(CBD)were significantly different(all P＜0.05)in patients with choledochal cyst type Ic compared to patients with distal choledochal obstruction.The CBD/LHD ratio and CBD/RHD ratio were significantly larger(P＜0.05).For patients with choledochal cyst type Ic,when compared with patients with simple gallbladder stones or polyps,the maximum diameter of CBD was significantly larger(P＜0.05),but the maximum diameters of LHD and RHD were not significantly different(both P＞0.05),while the ratios of CBD/LHD and CBD/RHD were significantly larger(P＜0.05).For patients with choledochal cyst type Ic,when compared with patients with simple gallbladder stones or polyps,the maximum diameter of CBD was significantly larger(P＜0.05),the maximum diameter of LHD and RHD was also significantly larger(P＜0.05),while the ratios of CBD/LHD and CBD/RHD were not significantly different(P＞0.05).The proportion of pancreaticobiliary maljunction(PBM)in patients with type Ic choledochal cyst was significantly higher than patients with distal choledochal obstruc-tion and simple gallstone or polyp(P＜0.05).Conclusions For patients with choledochal cyst type Ic,their CBD shows obvious dilation,while there is no obvious dilation in LHD and RHD,It is helpful to con-duct differential diagnosis of choledochal cyst type Ic by the use of MRCP to observe the presence of PBM and to quantitatively compare the CBD/LHD and CBD/RHD ratios.

How Microbes Shape Their Communities? A Microbial Community Model Based on Functional Genes / 基因组蛋白质组与生物信息学报·英文版

Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction (FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage (AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping (CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.

Anatomical development and clinical significance of the concept of porta hepatis / 中华肝胆外科杂志

The liver has complex blood supply and outflow system,mainly is composed of portal vein,hepatic artery,hepatic vein,short hepatic vein and inferior vena cava.At the initial stage of liver anatomy,the concept of "porta hepatis " refers specifically to the portal vein blood flow into the anatomical region of the liver.With the further study of liver anatomy and the need to adapt to the development of clinical practice of liver surgery,the concept of "porta hepatis" gradually extends to the blood inflow and outflow region.This article will review and discuss the anatomical development and clinical significance of "porta hepatis".