BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

With the widespread implementation of laparoscopic cholecystectomy in various levels of medical institutions, surgical complications have also increased. Among them, the incidence of bile duct injury remains high in complex laparoscopic cholecystectomy. The reason for this is that surgeons cannot effectively and accurately identify the relationship between the aberrant bile duct and the cystic duct and the common bile duct, resulting in the accidental injury of the bile duct, resulting in long hospital stays, increased medical costs, and decreased long-term quality of life for patients. Intraoperative cholangiography, as a real-time visual method of biliary presentation, can effectively reduce the incidence of iatrogenic bile duct injury. However, most surgeons do not fully understand the technology of intraoperative cholangiography during cholecystectomy. This article reviews the application of intraoperative cholangiography in laparoscopic cholecystectomy based on the clinical experience of the author′s team and the literature in recent years, with the aim of deepening the understanding of surgeons about intraoperative cholangiography, so as to better apply it to clinical practice and benefit patients.

In China, hepatocellular carcinoma (HCC) accounts for about 50% of cases in the world, which is still challenging. The implementation of multi-disciplinary treatment (MDT) and whole course management of HCC are conducive to improve the prognosis of patients, so as to achieve the goal of increasing by 15% of overall survival of HCC patients as proposed by the "Healthy China 2030" . The standardized management of HCC includes several key points, such as exact diagnosis of the HCC, selection of proper treatment methods, individual postoperative adjuvant therapy and regular follow-up. MDT is the key measure to implement the standardized and whole course management of HCC. Herein, the author tends to summary the experience on standardized management of HCC.

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/surgery* ; Guanine/analogs & derivatives* ; Hepatectomy ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Neoplasms/surgery* ; Retrospective Studies ; Tenofovir/therapeutic use*

Objective:To evaluate the long-term prognosis and recurrence of young liver transplant recipients with hepatocellular carcinoma(HCC).Methods:Based upon the database of liver transplantation center, clinical data were retrospectively reviewed for 39 young recipients(18~40 years)and 158 middle-aged and elderly recipients(over 40 years)from 2013 to 2017. The parameters of overall survival(OS), recurrence-free survival(RFS)and disease-specific survival(DSS)were compared between two groups.Cox's proportional hazard model was utilized for evaluating the prognostic factors.Results:Significant inter-group difference existed in recurrence rate of HCC. Kaplan-Meier analysis revealed no significant difference in OS rate(1/3-year OS, 82.1%, 66.7% and 86.1%, 74.7%, P>0.05)and DSS rate(1/3-year DSS, 94.9%, 82.1% and 99.4%, 91.1%, P=0.053); RFS rate(1/3-year RFS, 51.3%, 41.0% and 73.0%, 62.7%, P=0.008)showed significant differences; Cox multivariate analysis revealed that AFP>400 μg/L was an independent risk factor for OS, DSS and RFS; poorly differentiated tumors and positive micro-vascular invasion(MVI)were independent risk factor for DSS; poorly differentiated tumors and total tumor size >5 cm were independent risk factors for RFS. Conclusions:Although RFS of young adult group is worse than that in middle-aged and elderly group after LT, no significant inter-group difference exists in OS or DSS. And LT is still a quite effective treatment for young HCC patients.

Objective:To investigate the changes of genus-level gut microbiome in patients with spinal cord injury and its significance in clinical rehabilitation. Methods:Fecal samples were collected from 23 patients with spinal cord injury (patients group) and 21 healthy volunteers (control group). Gut microbiome was detected by 16S rDNA high-throughput sequencing. Bioinformatics methods such as species composition analysis and Random Forest were used to analyze the distribution and difference of genus-level gut microbiome between two groups. Results:Compared with the control group, the increased important marker genera in the patients group were as follows: UBA1819, Ruminiclostridium 9, Ruminococcaceae NK4A214 group, Ruminococcus 2, Ruminococceae UCG-005, Ruminiclostridium 5, Flavonifractor belonging to Ruminococceae; Aglistes, dgA-11 gut group, Rikenaceae RC9 gut group belonging to Rikenellaceae; [Eubacterium] oxidoreducens group belonging to Lachnospiraceae; Intestinibacter belonging to Peptostreptococcaceae; Escherichia-Shigella belonging to Enterobacteriaceae; Tannerellaceae belonging to Parabacteroides (|U| > 1.962, P < 0.05). The decreased marker genera in the patients group was Fusobacterium of Fusobacteriaceae (|U| = -2.284, P < 0.05). Conclusion:There are significant differences of gut microbiome in spinal cord injury patients. The relative abundance of Ruminococcaceae relating to depression, Ruminococcus relating to central nervous system diseases, and enteropathogenic bacteria such as Escherichia-Shigella and Erysipelothrix increase; and the relative abundance of butyrate-producing bacteria and anti-inflammatory bacteria benefitting to the intestine decrease; which may play a role in clinic.

BACKGROUND/AIMS: Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. METHODS: A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. RESULTS: The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson's capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities. CONCLUSIONS: These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.
Calibration ; Carcinoma, Hepatocellular ; Cohort Studies ; Disease-Free Survival ; Hepatectomy ; Humans ; Multivariate Analysis ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate

Objective To establish a clinical scoring system for the prognosis of patients with single large hepatocellular carcinoma (HCC) after hepatectomy.Methods 268 patients with single large HCC who underwent hepatectomy in West China Hospital of Sichuan University from January 2009 to December 2013 were included in this prospective study. There were 227 males and 41 females, of which 198 cases aged≤60 years old, 70 aged>60 years old. The informed consents of all patients were obtained and the local ethical committee approval was received. The patients' survival were observed. The independent risk factors for postoperative prognosis of patients with single large HCC were selected by Cox proportional risk regression mode. Based on the risk factors, the prognostic scoring system for single large HCC wasestablished. The scoring system was tested through survival analysis by Kaplan-Meier and Log-rank test. Results The median overall postoperative survival was 45 months, and the tumor-free survival was 31 months. Platelet-to-lymphocyte ratio (PLR)≥107, tumor diameter≥6.8 cm and positive microvascular invasion (MVI) were the independent risk factors for postoperative overall survival and tumor-free survival in patients with single large HCC (HR=1.004, 1.092, 2.233 and 1.003, 1.062, 1.534; P<0.05). Every independent risk factor was assigned 1 point. All patients were divided into low risk group (0 point), moderate risk group (1-2 points) and high risk group (3 points). The 5-year survival rate of high risk group was 25.4％, and that of moderate and low risk group was 33.2％ and 52.1％ respectively, where significant difference was observed (χ2=23.1, P<0.05). Similar Results were observed when the scoring system was used in patients with or without cirrhosis.Conclusions PLR≥107, tumor diameter≥6.8 cm and positive MVI are the independent risk factors for the prognosis of patients with single large HCC after resection. The prognostic scoring system established in this study can be used to predict the postoperative long-term survival of patients.

BACKGROUND/AIMS: Solitary hepatocellular carcinoma (HCC) is a subgroup of HCCs. We aimed to establish nomograms for predicting the survival of solitary HCC patients after hepatectomy. METHODS: A total of 538 solitary HCC patients were randomly classified into training and validation sets. A Cox model was used to identify predictors of overall survival (OS) in the training set. A nomogram was generated based on these predictors and was validated using the validation set. RESULTS: Tumor size, microvascular invasion, and major vascular invasion were significantly associated with OS in the training set. Nomograms were developed based on these predictors in the multivariate analysis. The C-index was 0.75 for the OS nomogram and 0.72 for the recurrence-free survival nomogram. Compared to the index of conventional staging systems for predicting survival (0.71 for Barcelona Clinic Liver Cancer, 0.66 for the seventh American Joint Committee on Cancer, 0.68 for Cancer of the Liver Italian Program, and 0.70 for Hong Kong Liver Cancer), the index of the OS nomogram was significantly higher. Moreover, the calibration curve fitted well between the predicted and observed survival rate. Similarly, in the validation set, the nomogram discrimination was superior to those of the four staging systems (p<0.001). CONCLUSIONS: The nomograms demonstrated good discrimination performance in predicting 3- and 5-year survival rates for solitary HCCs after hepatectomy.
Calibration ; Carcinoma, Hepatocellular* ; Discrimination (Psychology) ; Hepatectomy* ; Hong Kong ; Humans ; Joints ; Liver ; Liver Neoplasms ; Multivariate Analysis ; Nomograms* ; Prognosis ; Survival Rate

Objective To evaluate the value of acoustic radiation force impulse (ARFI) elastography in assessment of nonalcoholic fatty liver disease (NAFLD) and hepatic fibrosis in rats.Methods Models with various degrees of NAFLD severity were conducted in 110 rats by feeding high fat emulsion.The right liver lobe of rat models were processed and embedded in a fabricated gelatin solution to measure the shear wave velocity (SWV) by ARFI.And the other liver lobes were used for histologic assessment.Based on NAFLD activity score (NAS),the final pathologic NAFLD diagnosis were considered as normal group (NAS=0),simple steatosis (SS) group (1≤NAS≤2),borderline (3≤NAS≤4) group and nonalcoholic steatohepatitis (NASH) group (NAS≥5).The diagnostic accuracy of the SWV parameters in evaluating NAFLD severity and fibrosis stages was studied using ROC curves.Results The difference of SWV values among normal group,SS group,borderline group and NASH group was statistically significant (F=31.53,P＜0.001).Taking SWV≥ 2.54 m/s as the diagnostic standard to differentiate normal rats from rats with SS,and SWV≥2.90 m/s to differentiate SS from NASH in rats,the area under ROC curve (AUC) was 0.922 (95％CI [0.871,0.973],P＜0.001) and 0.882 (95％ CI [0.807,0.956],P＜0.001) respectively.The sensitivity and specificity were 93.5 ％ and 100 ％ for differentiating normal and SS groups,83.3 ％ and 84.2 ％ for differentiating SS and NASH groups.Taking SWV≥3.48 m/s as cutoff to predict fibrosis (≥F2 stage),the AUC was 0.963 (95％CI [0.909,1.000],P＜0.001),the sensitivity was 92.9％ and the specificity was 97.6％.Taking SWV≥3.61 m/s as cutoff to predict severe fibrosis (≥F3 stage),the AUC was 0.997 (95％CI [0.990,1.000],P＜0.001),sensitivity was 100％ and specificity was 98.9％.The same high validity was maintained as in the prediction of cirrhosis (F4 stage) with the cutoff as SWV≥4.50 m/s,and the AUC was 0.993 (95％CI [0.982,1.000],P＜0.001),the sensitivity was 100 ％ and the specificity was 96.8％.Conclusion ARFI elastography is a promising method for differentiating the different severity of NAFLD and staging the degree of hepatic fibrosis with NAFLD in rat models.