Objective To explore the roles of transcription factor E26 transformation-specific 1(ETS1)and F-box protein 45(FBXO45)in invasion and metastasis in hepatocellular carcinoma cells and the potential molecular mechanism.Methods Jaspar,hTFtarget and Cistrome transcription factor database prediction websites were used to predict the transcription factors of FBXO45.According to the intersection of the predicted results of each database,the expression of FBXO45 was detected after the candidate transcription factors were knockdown in HCCLM3 and Huh7 liver cancer cells,respectively.The most significant influence on FBXO45 expression was selected for further analysis,and chromatin immunoprecipitation assay(ChIP)was used to verify the binding to the FBXO45 promoter.Finally,the potential transcription factor of FBXO45 was identified.The effect of ETS1 overexpression on invasion and migration in HCCLM3 and Huh7 cells was detected by Transwell assay,and the expression levels of epithelial-mesenchymal transition(EMT)pathway proteins were detected by Western blot assay.The effects of FBXO45 knockdown on the invasion and migration under the condition of overexpression of ETS1 were also studied.Results Intersection of FBXO45 transcription factors identified 3 candidate transcription factors,ETS1,SPI1 and YY1.When the 3 transcription factors were knocked down in HCCLM3 and Huh7 cells,respectively,ETS1 knockdown significantly reduced the expression of FBXO45.According to the analysis of The Cancer Genome Atlas(TCGA)data and the Gene Expression Omnibus(GEO)data,the expression levels of ETS1 and FBXO45 were significantly positively correlated(R=0.31,P<0.000 1;R=0.40,P=0.021 9).ChIP suggested that ETS1 could specifically bind to FBXO45 promoter sequence to regulate its expression,confirming that ETS1 was a potential transcription factor of FBXO45.After overexpression of ETS1 in HCCLM3 and Huh7 cells,the invasion and migration abilities of cells were significantly enhanced,and the expression of N-cadherin and Snail was up-regulated(P<0.01).In addition,in the case of ETS1 overexpression,FBXO45 knockdown significantly inhibited the invasion and migration(P<0.01).Conclusion ETS1 activates the transcription of FBXO45 and leads its high expression,which enhances the invasion and migration of HCC cells via EMT pathway and promotes the progression of hepatocellular carcinoma.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To analyze the clinical efficacy and safety of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and PD-1 antibody in the treatment of intermediate-advanced hepatocellular carcinoma(HCC).Methods A retrospective cohort trial was conducted on 105 patients with intermediate-advanced HCC(BCLC B or C stage)treated with TACE combined with lenvatinib and PD-1 antibody in our institute from January 2021 to June 2023.The blood biochemical indicators and imaging characteristics of the patients were collected before and after TACE.Objective response rate(ORR),disease control rate(DCR),conversion resection rate,overall survival(OS)and progression-free survival(PFS)were analyzed to evaluate the clinical efficacy of the triple therapy,and the frequency and severity of all adverse reactions during treatment were recorded to evaluate the safety of the therapy.Results Among the 105 patients with intermediate-advanced HCC who received triple therapy,33 died and 72 survived.The ORR was 62.8％and the DCR was 72.3％.The conversion resection rate was 11.4％.The median OS(mOS)was not reached.The median PFS(mPFS)was(10.3±0.8)months.The incidence of adverse reactions of all grades was 97.1％,and the incidence of those of grade 3～4 was 33.3％.No treatment-related death occurred.Conclusion The triple therapy of TACE combined with lenvatinib and PD-1 antibody is a safe and effective comprehensive treatment regimen,which provides a new treatment strategy for improving the prognosis of intermediate-advanced HCC.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Objective:To investigate the application value of digital single-operator peroral cholangioscopy on the preoperative evaluation of extrahepatic cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 172 patients with extrahepatic cholangiocarcinoma who were admitted to the First Affiliated Hospital of Army Medical University from December 1, 2017 to April 1, 2022 were collected. There were 91 males and 81 females, aged 65(range, 45?68)years. Of 172 patients, 36 cases undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the experimental group, and 136 cases not undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the control group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) surgical conditions. Propensity score matching was done by the 1:1 nearest neighbor matching method and caliper setting as 0.02. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1,Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 172 patients, 60 cases were successfully matched, including 30 cases in the experiment group and 30 cases in the control group, respectively. Before propensity score matching, cases with or without preoperative bile drainage were 27, 9 in the experiment group, versus 62, 74 in the control group, showing a significant difference between the two groups ( χ2=9.86, P<0.05). The above indicators were 23, 7 in the experiment group, and 23, 7 in the control group after propensity score matching, showing no significant difference between the two groups ( χ2=0.00, P>0.05). The elimination of preoperative bile drainage confounding bias ensured comparability between the two groups. (2) Surgical conditions. After propensity score matching, there were 10 cases and 0 case without surgery in the two groups. Cases undergoing radical operation including R 0, R 1, R 2 resection were 16, 0, 4 in the experiment group, versus 18, 6, 6 in the control group, showing a significant difference between the two groups ( χ2=6.85, P<0.05). Conclusions:Preoperative digital single-operator peroral cholangioscopy exami-nation can improve the R 0 resection rate of extrahepatic cholangiocarcinoma.

Objective:To explore the etiology, pathogenesis, clinical features, diagnosis and treatment of hepatic sinus obstruction syndrome(HSOS)after orthotopic liver transplantation(OLT).Methods:Clinical data were reviewed for 3 HSOS patients after OLT.Baseline profiles, primary disease, onset, clinical manifestations, abdominal imaging and pathological changes were recorded for summarizing the key points of diagnosis, treatment and outcomes of HSOS after OLT.Results:HSOS was an extremely rare complication after OLT with an incidence of 2%(2/117)and a median onset of 15(13-50)days.The major clinical manifestations were hepatic pain, abdominal distension, poor appetite, fatigue, jaundice, oliguria, peritoneal effusion and pleural effusion.Some of them were complicated with acute renal insufficiency.Abdominal ultrasonography revealed that blood stream of hepatic and portal veins was smooth but rather slow and hepatic parenchyma showed uneven echo changes.Abdominal enhanced computed tomography(CT)demonstrated " mosaic" and " map-like" uneven enhancement in portal vein and balance phases.The pathological manifestations of liver biopsy included obvious dilation and congestion of hepatic sinuses, swelling and necrosis of hepatic cells, thickening of hepatic venules and luminal stenosis or occlusion.All of them received immunosuppressants.Tacrolimus was switched to sirolimus, low molecular weight heparin or plus rivaroxaban anticoagulant thrombolytic therapy, methylprednisolone regulatory immunotherapy, albumin supplementation, diuresis, hepatic protection and fluid replacement.Afterward clinical symptoms of 2 patients improved, became cured and discharged.One case died from gastrointestinal hemorrhage and acute renal failure secondary to multiple organ failure.Conclusions:HSOS is an extremely rare but severe complication after OLT.Early diagnosis and fine-tuning of treatment protocols can avoid poor prognosis such as liver and kidney failure and significantly improve patient survival.

Benign biliary strictures (BBSs) is a kind of difficult clinical problem in biliary surgery. Surgery and endoscopic treatment are common diagnostic and therapeutic methods. The rapid development of endoscopic technology challenges the traditional surgery. How to integrate surgery and endoscopic technology in an orderly manner and develop strengths and circumvent weaknesses requires a breakthrough in guiding ideas. The precision surgery, with the characteristics of certainty, predictability, controllability, standardization, individualization and systematization, has become an ideal choice for integrating surgery and endoscopic technology. Based on clinical practice, the authors discuss the endoscopic diagnosis and treatment strategy of BBSs from the perspective of precision surgery by implementing the core elements of precision surgery.

The diagnosis and treatment of complex biliary and pancreatic diseases is still one of the major problems and challenges faced by modern medicine. The concept of "precision surgery" proposed by academician Jiahong Dong provides a new way to solve this problem. With the rapid development of biliary and pancreatic endoscopy, it has become an important vehicle for the diagnosis and treatment of complex biliary and pancreatic diseases. In recent years, the authors have combined accurate endoscopy with precision surgery in the treatment of clinical complex biliary and pancreatic diseases, achieving good effects.

Objective:To evaluate combining fistula risk score(FRS) with drain fluid amylase on postoperative day 1(DFA1) in predicting clinically relevant postoperative pancreatic fistula(CR-POPF) following pancreaticoduodenectomy(PD).Methods:The clinical data of 430 patients who underwent PD in the First Affiliated Hospital of Amy Medical University from Jan 2013 to Oct 2015 was retrospectively analyzed, receiver operating characteristic curve(ROC curve) was used to test whether the FRS predicts the CR-POPF, and DFA1 was employed to predict the CR-POPF in the moderate/high subgroup patients(FRS 3-10).Results:Fifty six patients(13.0%) had CR-POPF, the ROC curve for FRS predicting CR-POPF was formed with area under curve 0.894(95% CI: 0.861-0.921, P<0.001), the results from univariate and multivariate logistic regression analysis showed that FRS was independent risk factor associated with CR-POPF ( OR=2.933, 95% CI: 2.230-3.856, P<0.001). After dividing 430 patients into 2 groups by FRS category, there was no CR-POPF in negligible/low subgroup patients(FRS 0-2), and FRS>2 predicted CR-POPF with negative predictive value 100%; in moderate/high subgroup patients(FRS 3-10), ROC curve worked out DFA1>653.9 U/L predicting CR-POPF well with sensitivity, specificity, positive and negative predictive value of 87.5%, 63.8%, 39.2%, 95.0%, respectively. Conclusion:For patients with FRS≤2, and FRS≥3 accompanying DFA1≤650 U/L, early removal of intra-abdominal drains after PD is safe.

Advanced intrahepatic cholangiocarcinoma(ICC) is one of the most common hepatic malignant tumors besides hepatocellular carcinoma, with occult onset, limited treatment and poor prognosis. Systemic treatment is a recommendable solution for advanced unresectable ICC. The authors reported the clinical experience of an ICC patient who underwent transarterial chemoembolization combined with immunotherapy plus target therapy.