INTRODUCTION:Several techniques are used for laparoscopic treatment of gallstone disease with biliary duct stone, but each approach has indications and shortcomings. We have developed a modified laparoscopic transcystic biliary drainage for the management of cholecysto-choledocholithiasis. The hypothesis is that the modified laparoscopic transcystic biliary drainage will reduce morbidity from around 15% to less than 5%. The aim of this study is to assess the safety and efficacy of the modified laparoscopic transcystic biliary drainage. METHODS AND ANALYSIS:This is a prospective single-arm clinical trial to evaluate the safety and efficacy of the modified laparoscopic transcystic biliary drainage. The recruited 310 patients will be from Peking University Third Hospital. (Here, patients who meet the inclusion criteria will be included in the study, all patients will undergo laparoscopic cholecystectomy with concomitant laparoscopic exploration of the common bile duct and a modified laparoscopic transcystic drainage.) The primary endpoint is the postoperative morbidity and bile leakage. The secondary endpoints of the study are anchoring time of the C-tube, average daily drainage volume, early dislodgement of the C-tube, removal time of the C-tube, pancreatitis, residual stones and postoperative hospital stay. Recurrent stones and biliary stricture will be recorded during 6 months of follow-up. A two-tailed p<0.05 was considered statistically significant. SPSS for Windows V.21.0 (SPSS) software was used. ETHICS AND DISSEMINATION:This clinical trial was approved by the Medical Science Research Ethics Committee of Peking University Third Hospital (No. M2023223). TRIAL REGISTRATION NUMBER:NCT06011941. PROTOCOL VERSION:V.2, 23 November 2023.

Background Bilateral hepatolithiasis is an intractable disease and repeated attacks of acute cholangitis seriously threaten patient health. The surgical approaches evolve along with gradually greater understanding of its pathophysiology. Methods This is a retrospective cohort study for bilateral hepatolithiasis from January 1958 to December 2018. Before May 1993 (Group A, n = 70), three surgical approaches were adopted: 37 patients with common bile duct exploration (CBDE), 29 with choledochoenterostomy (CE) and four with partial hepatectomy (PH). After June 1993 (Group B, n = 150), 101 patients underwent Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), and 16 with CBDE, 21 with CE, 12 with PH. The perioperative and long-term outcomes were compared. Results After 1993, the cholangitis recurrence rate significantly decreased from 49.2% to 20.9%, and the stone recurrence rate from 76.3% to 37.1% (both P < .001). Also, the stone-/cholangitis-free durations were prolonged significantly (median: 50.8 vs 26.4/49.6 vs 16.2 months, both P < .001). Preoperative cholangitis was an independent risk factor for stone recurrence (hazard ratio [HR] = 1.863, P = .018), and residual stone for cholangitis recurrence (HR = 2.838, P < .001). OSPCHS and PH were protective surgical approaches for recurrent stone (CBDE: reference; OSPCHS: HR = .469, P = .016, PH: HR = .219, P = .018) and cholangitis (CBDE: reference; OSPCHS: HR = .421, P = .010, PH: HR = .283, P = .093). Conclusions For bilateral hepatolithiasis, the management should focus on hepatobiliary lesion eradication and Oddi sphincter function preservation.

Background: Anillin (ANLN) is required for tumor growth. It has been proven that knockdown of ANLN effectively reduces the occurrence of hepatocellular carcinoma (HCC) in transgenic mice. However, the functional role of ANLN in HCC patients remains to be elucidated. Methods: Both microarray and TCGA project were used for the analyses of ANLN expression and regu-lation in HCC. The effect of ANLN on proliferation and cell cycle was detected by CCK-8, colony forma-tion assay and flow cytometry. ANLN expression was measured by immunohistochemistry. Correlation between ANLN expression and clinicopathological features was assessed by Pearson Chi-square test and 5-year overall survival after liver resection was evaluated by Kaplan-Meier method. Results: Increased copy number, decreased methylation levels in the CpG island and upregulated histone hypermethylation of ANLN were found in HCC. Knockdown of ANLN inhibited proliferation and induced G2/M phase arrest in SMMC-7721 cells. ANLN was mainly expressed in the nucleus and showed sig-nificantly higher expression levels in cancerous tissues than those in paired adjacent tissues. Moreover, nuclear ANLN expression levels in HCC metastases were significantly higher than those in primary HCC. The results of Cox proportional hazards regression model suggested that ANLN nuclear expression in HCC was an independent risk factor for poor 5-year overall survival of patients after liver resection. Conclusions: ANLN is a potential therapeutic target for HCC. Patients with nuclear ANLN overexpression in HCC tissue may need adjuvant therapy after liver resection. (c) 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.

Objective To summarize the experience of diagnosis and treatment of rare type of hepatic benign space occupying lesions.Methods The clinical data of 113 patients with rare type of hepatic benign space occupying lesions confirmed by surgery and pathology from Jan 2009 to Dec 2018 were retrospectively analyzed.Results There were 51 males and 62 females,age ranging from 12 to 83 years,with an average of 44.3 years.91.2％ of the 113 cases were single lesions and 8.8％ were multiple lesions.Surgical methods included hepatectomy in 98 cases,ablation therapy in 12 cases and hepatectomy combined with ablation in 3 cases.There were 21 types of pathology in 113 patients.The top five types were focal nodular hyperplasia (30 cases),hepatocellular adenoma (16 cases),dysplasia nodules (14 cases),perivascular epithelioid cell tumors (12 cases),and mucinous cystic neoplasms (11 cases),accounting for 73.5％ cases.All the patients were alive in the follow-up period ranging from 6 to 120 months.Conclusion Preoperative diagnosis of rare benign space-occupying lesions of the liver is very difficult.Preoperative MRI is helpful for diagnosis.Conservative treatment or follow-up observation can be considered for the type malignancy have never been reported.For the borderline types or those with difficulty in definite diagnosis,surgical removal is recommended.

Introduction: Choledocholithiasis is usually treated with endoscopic sphincterotomy (EST), laparoscopic common bile duct exploration (CBDE) (LCBDE), or laparoscopic transcystic CBDE (LTCBDE). However, the comparative long-term prognosis of these methods in terms of adverse outcomes remains uncertain. Methods: In an ambispective, multicenter, observational, open cohort study, patients with cholecystocholedocholithiasis underwent one of three treatments (EST+laparoscopic cholecystectomy (LC), LCBDE+LC, and LTCBDE+LC).The primary outcome was adverse outcomes. Results: At a median follow-up period of 2.72 years among 2708 patients, the adverse outcome rate is 9.3%. Compared with LCBDE and LTCBDE groups, EST group displayed an increased risk for adverse outcomes (HR 1.25, 95% CI 0.93-1.69, P=0.146; HR 1.77, 95% CI 1.30-2.43, P<0.001) and stone-related outcomes (HR 1.43, 95% CI 0.99-2.06, P=0.054; HR 4.36, 95% CI 2.71-7.02, P<0.001) in the unadjusted Cox model. After adjustment in the multivariable analysis, EST group still displayed an increased risk of adverse outcomes (HR 1.43, 95% CI 1.05-1.95, P=0.021; HR 1.87, 95% CI 1.35-2.59, P<0.001) and stone-related outcomes (HR 1.64, 95% CI 1.13-2.37, P=0.010; HR 4.88, 95% CI 2.99-7.97, P<0.001). Compared with LTCBDE group, LCBDE group displayed an increased risk for a stone-related outcome in both the unadjusted Cox model (HR 3.05, 95% CI 1.89-4.90, P<0.001) and the adjusted multivariable analysis (HR 2.98, 95% CI 1.83-4.86, P <0.001). Conclusion: Compared with EST, the laparoscopic technique was associated with a lower risk of adverse outcomes and stone-related outcomes after adjustment for confounding factors. In laparoscopic techniques, the risk of stone-related outcomes after LTCBDE is reduced 66.4% than LCBDE. Clinical Trial Registration: CREST Choles ClinicalTrials.gov number, NCT02554097. Funding Statement: The author(s) disclose receipt of the following financial support for the research, authorship, and/or publication of this article: this program is sponsored by Capital Health Research and Special Development (No. 2016-1-1111), National Key Technologies R&D Program (No. 2015BAI13B09), and Beijing Municipal Administration of Hospitals Incubator Program (No. PX2016001 and No. PX2019004). Declaration of Interests: The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: Ethical approval was obtained at all participating centers.

Objective To explore the feasibility and safety of laparoscopic transcystic common bile duct stone extraction and cholecystectomy in pregnant patients with choledocholithiasis.Methods A retrospective analysis of 4 pregnant patients with choledocholithiasis was performed.The clinicoradiologic,perioperative and follow up data were analyzed.Results The 4 patients were admitted for acute cholangitis at their second trimester of pregnancy.Preoperative MRCP demonstrated that the diameter of the common bile duct stone was less than that of the cystic duct.Laparoscopic transcystic common bile duct stone extraction and cholecystectomy were successfully conducted.Plasma shock wave lithotripsy was applied in one patient with impacted gallstone,intraoperative cholangiography was conducted in one patient with suspected residual stone.There was not major post-op complications nor stone recurrence in the follow up postoperatively.They all delivered a healthy baby on the expected date of childbirth.Conclusions Simutaneously laparoscopic transcystic common bile duct stone extraction and cholecystectomy in pregnant patients with choledocholithiasis is feasible and safe.

Objective To evaluate the effect and feasibility of simulation teaching on the acquisition and retention of basic surgical clinic skills for eight-year medical program.Methods 46 clinical medical students of eight-year medical program in 2012 grade in Peking University Third Hospital were randomized to a simulation training (experimental group) or a traditional teaching (control group) for surgical skill training curriculum during a period of 3 weeks.Students were tested with objective structured assessment of technical skills (OSATS) scoring system after training and 1 year later.Results 46 students completed all models training and post-training assessments.OSATS scores were higher in experimental group compared with control group (t=9.194,P=0.001).After 1 year,this effect persisted with OSATS scores still being significantly higher in experimental group (t =14.140,P=0.001).The simulation teaching method was approved by most of students through the questionnaire survey.Conclusions Simulation teaching improves technical efficiency.Retesting can further evaluate advantages of simulation teaching.

Hepatic stellate cells (HSCs) play an important role in liver fibrosis. This study investigates the expression of hedgehog in HSC and the role of hedgehog signaling on activation and collagen secretion of HSC. Liver ex vivo perfusion with collagenase IV and density gradient centrifugation were used to isolate HSC. Expression of hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 in HSC were detected by RT-PCR. Hedgehog siRNA vectors targeting Ihh, Smo and Gli2 were constructed and transfected into HSC respectively. Suppression of hedgehog signaling were detected by SYBR Green fluorescence quantitative RT-PCR. Effects of hedgehog signaling inhibition on HSC activation and collagen I secretion were analyzed. Hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 were expressed in HSC. siRNA vectors targeting Ihh, Smo and Gli2 were successfully constructed and decreased target gene expression. Suppression of hedgehog signaling significantly decreased the expression of α-SMA in HSC (P<0.01). Collagen type I secretion of HSC were also significantly decreased (P<0.01). In summary, HSC activation and collagen secretion can be regulated by hedgehog signaling. Hedgehog may play a role in the pathogenesis of liver fibrosis.

BACKGROUND The coagulation function in patients with pancreatic carcinoma is abnormal and the reason is not very clear. In this study, we retrospectively analyzed the coagulation function in patients with pancreatic carcinoma. METHODS From June 2004 to December 2007, 132 patients received diagnosis and treatment in our hospital. The coagulative parameters including the prothrombin time, activated partial thromboplastin time, and fibrinogen levels were collected and studied retrospectively. RESULTS The average fibrinogen levels in patients with pancreatic carcinoma, (476.21 +/- 142.05) mg/dl, were significantly higher than in patients with cholangiolithiasis, (403.28 +/- 126.41) mg/dl (P < 0.05). In patients with pancreatic carcinoma, the levels of fibrinogen in the group with jaundice were significantly higher than in patients without jaundice (P < 0.05). In patients who received Pancreaticoduodenectomy, Whipple's operation, the level of fibrinogen in the group with local invasiveness was significantly higher than in the group without invasiveness. The group with lymphatic metastasis had higher levels than the group without lymphatic metastasis (P < 0.05). There was no significant difference of intraoperative blood loss between patients with vitamin K, (748.27 +/- 448.51) ml, and those without vitamin K, (767.31 +/- 547.89) ml (P > 0.05). CONCLUSIONS The level of fibrinogen in patients with pancreatic carcinoma was elevated. The elevated fibrinogen level may be associated with invasiveness and lymphatic metastasis. Using vitamin K in perioperation management did not reduce intraoperative blood loss.

Despite the wide acceptance of laparoscopic resection of abdominal tumors, few cases of laparoscopic removal of retroperitoneal schwannoma have been reported to date. We present a case of retroperitoneal schwannoma, encircled with the celiac artery, common hepatic artery, splenic artery, splenic vein, and portal vein, which was resected successfully using laparoscopic surgical technique. During the procedure, an attempt was made to approach the neoplasm via the inferior border of the pancreas, but it was hard to separate the superior mesenteric vein. We changed the position to separate the tumor from the anterior border of the splenic vein with success. Without any complications, the patient was discharged on the sixth postoperative day. In contrast to the open procedure for resection of a tumor in this location, laparoscopy has the advantage of precise visualization, which helps to resect retroperitoneal schwannoma completely.

Objective To study the expression of Hedgehog signal pathway in rat hepatic stellate cell (HSC) line rHSC-99. The method of RNAi was adopted to inhibit Hedgehog signal pathway,and estimate the regulation role of Hedgehog signal pathway in activation and proliferation of HSC. Methods RTPCR was used to detect the expression of Hedgehog signal pathway in rat HSC line rHSC-99. Transcripts of siRNA sequence of the genes Ihh,Smo,and Gli2 were designed,and transfected into HSC respectively. Then the expression of these mRNAs were detected by SYBR green flurogenic quantitative PCR. The expression of α-SMA was detected by Western blot. The variation of type I collagen in culture supernatant of HSC was detected by ELISA. The proliferation of HSC was measured by MTT assay. Results HSC expressed mRNAs of Ihh,Smo,Ptc,Gli2,Gli3. The expression of these mRNAs could be reduced by trans-fecting plasmids encoded siRNA of Ihh,Smo or Gli2 (0. 254 ±0.130,0.221 ±0. 150,0. 235 ±0. 110 vs 1 ,P<0.01). Transfection experiment demonstrated the reduction of the expression of α-SMA (0. 191 ± 0.014,0. 357 ± 0. 021,0. 086 ± 0. 016 vs 1. 143 ± 0. 017, P<0. 01) and secretion of collagen I (22.9±2.0,16.4±1.4,17.6±1.8 vs 40.7 ±4.3,P<0.01) in HSC,and HSC proliferation was decreased (0.204 ±0.019,0. 226 ±0. 014,0. 228 ±0.015 vs 0. 412 ±0. 016,P<0.05). Conclusion This study showed the expression of Hedgehog signal pathway in HSC. Down-regulation of Hedgehog signal pathway may inhibit HSC activation and proliferation. Key words: Hepatic stellate cell; Signal pathway; Proliferation

Introduction: Gallbladder adenomyomatosis (ADM) is a non-neoplastic, non-inflammatory disease. Herein, we retrospectively analyzed pathologically confirmed cases of 15 years in our center to investigate the diagnosis and treatment of ADM. Method: Data of patients who received cholecystectomy and were pathologically confirmed to have gallbladder adenomyomatosis were retrieved from the pathological database of Peking University Third Hospital from January 1, 2003 to December 31, 2017. The epidemiology, clinical manifestation, imaging examinations, surgical treatments and pathological features of these patients were analyzed retrospectively. Result: Of the 14,454 patients who underwent cholecystectomy, 478 were pathologically confirmed to have gallbladder adenomyomatosis, with a detection rate of 3.3%. There were 369 cases (77.2%) with symptoms, 279 cases (58.4%) with gallbladder stones, and 2 cases (0.4%) with common bile duct stones. The preoperative diagnostic rates of ultrasound, contrast-enhanced computed tomography(CT), magnetic resonance cholangiopancreatography(MRCP) or contrast-enhanced magnetic resonance imaging(MRI) were 25.4% (108/425), 40.6% (58/143) and 45.8%(148/323), respectively. The diagnostic rate of ultrasound combined contrast-enhanced CT, MRCP or contrast-enhanced MRI were 64.1% (50/78). Laparoscopic cholecystectomy (LC) was performed in 436 cases (91.2%), with 1 case of common bile duct exploration, 1 case of endoscopic sphincterotomy(EST) on common bile duct stone, and 1 case of hepatoduodenal ligament lymph node dissection. Open cholecystectomy was performed in 42 cases (8.8%). There were 58 cases (12.1%) with cholesterol polyps or cholesterol deposition, 12 cases (2.5%) with gallbladder adenoma, and 2 cases (0.4%) with gallbladder carcinoma. Pathologically, 287 cases were classified into fundal type (239 cases, 83.3%), segmental type (27 cases, 9.4%), and diffuse type (21 cases, 7.3%). Conclusion: Gallbladder adenomyomatosis is often accompanied with gallbladder stones. Ultrasound combined with contrast-enhanced CT, MRCP or contrast-enhanced MRI can improve the diagnostic rate. Currently LC is the main procedure for the treatment of adenomyomatosis of gallbladder.