Abstract:Objective: To investigate the difference in efficacy between primary closure and T-tube drainage following laparoscopic cholecystectomy (LC) with laparoscopic common bile duct exploration (LCBDE) in treatment of gallbladder stones combined with common bile duct stones. 
Methods: The clinical data of 218 patients undergoing LC+LCBDE from April 2013 to April 2018 were retrospectively analyzed. Of the patients, 90 cases underwent primary closure of the common bile duct and 128 cases were subjected to T-tube drainage. The main clinical variables between the two groups of patients were compared, and the factors for the occurrence of complications were analyzed.
Results: There were no significant differences in preoperative general data, intraoperative blood loss, time to first postoperative anal gas passage, incidence of postoperative electrolyte disturbance and residual stone rate between the two groups (all P>0.05). In primary closure group, the operative time, length of postoperative hospital stay and hospitalization cost were reduced, but the time for postoperative abdominal drainage was prolonged significantly compared with T-tube drainage group (all P<0.05). In primary closure group versus T-tube drainage group, the incidence of postoperative bile leakage was significantly higher (8.89% vs. 2.34%, P=0.030), while the incidence of postoperative stone recurrence rate was significantly lower (1.11% vs. 7.03%, P=0.040). Statistical analysis showed that primary closure was an independent risk factor for the occurrence of postoperative bile leakage, and T-tube drainage was an independent risk factor for the occurrence of stone recurrence (both P<0.05).
Conclusion: In LC+LCBDE, primary closure can effectively reduce the recurrence of postoperative common bile duct stones, while T-tube drainage can effectively reduce the incidence of postoperative bile leakage. These two methods cannot entirely be replaced by each other, and the indications should be rigorously followed.

Abstract:Objective: To investigate the feasibility and efficacy of retrograde tracing along the cystic duct to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC).  
Methods: Three hundred and twenty-four patients undergoing LC were selected. The approach of retrograde tracing along the cystic duct was performed in all patients during operation, namely, after the supposed cystic duct was isolated, retrograde dissection closely along this duct toward the gallbladder was performed, and if this  duct was verified to be the true cystic duct, it was clamped and then cholecystectomy was performed, but if this was not the cystic duct, the anatomical pathway was changed to seek the cystic duct for prevention of BDI up to the completion of cholecystectomy.
Results: Of the 324 patients, the supposed cystic duct was verified to be the actual cystic duct or its safety site in 319 cases, was found actually to be the common hepatic (bile) duct in 3 cases, and aberrant right posterior hepatic duct opening into the cystic duct in 2 cases. LC was uneventfully performed in all the 324 patients. The average operative time was 64.3 (25–210) min, and the average blood loss was 7.3 (2–150) mL.Postoperative minor bile leakage and fluid collections in the gallbladder region occurred in one patient, which were cured by puncture drainage and wound dressing. No BDI was found in the other patients. The average length of postoperative stay was 2.6 (1–13) d. No jaundice or abdominal pain was noted in the patients during one-moth follow-up.
Conclusion: Retrograde tracing along the cystic duct for prevention of BDI during LC is safe and reliable as well as easy to perform. It can be used as a supplement to other preventive methods. 

Abstract:Objective: To compare the clinical efficacy of using unidirectional barbed suture (UBS) and traditional suture (TS) in primary closure of the common bile duct following laparoscopic common bile duct exploration (LCBDE).  
Methods: The clinical studies comparing using UBS and TS in LCBDE with primary choledochal closure published in English and Chinese were searched through online databases. The retrieval time was up to September 2018. After the quality evaluation and data extraction of the included studies, Meta-analysis was performed by using RevMan 5.1 and STATA 12.0 software.
Results: Ten studies were finally included with three randomized controlled trials (RCTs) and seven observational studies, involving a total of 848 patients. The results of overall analysis showed that the time for bile duct suturing (WMD=–11.38, 95% CI=–14.81––7.94, P<0.001), operative time (WMD=–20.55, 95% CI= –30.63––10.46, P<0.001) and length of hospital stay (WMD=–0.78, 95% CI=–1.47––0.09, P<0.05) were all shortened, and the incidence of bile leakage (RR=0.23, 95% CI=0.10–0.55, P<0.001) was decreased significantly in UBS group compared with TS group. The results of subgroup analyses based on study design showed that except the length of hospital stays had no statistical difference between the two groups (WMD=–0.06, 95% CI=–0.61–0.49, P=0.83), all the others were consistent with the results of overall analysis. 
Conclusion: UBS not only provides a new approach for laparoscopic primary choledochal closure, but also is feasible and safe. However, this conclusion still needs to be verified by more multicenter and well-designed randomized controlled trials.

Abstract:Objective: To investigate the efficacy and safety of laparoscopic transcystic duct micro-incision and primary closure for stone at the junction of the cystic duct and common hepatic duct. 
Methods: The clinical data of 8 patients with stone at the junction of the cystic duct and common hepatic duct treated in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Inner Mongolia Medical University from December 2015 to December 2017 were reviewed. All patients underwent laparoscopic cholecystectomy and micro-incision via cystic duct with primary closure, and some of them were assisted by choledochoscopic operation. The operative time, intraoperative blood loss, time to postoperative gastrointestinal functional recovery, time to drainage tube removal, length of postoperative hospital stay and incidence of complications were analyzed. The patients were followed up for 3 to 24 months after surgery.
Results: Laparoscopic operations were successfully performed in all the 8 patients, without any open conversion. The operative time was (125.5±24.2) min, time to postoperative gastrointestinal functional recovery was (28.9±8.2) h, time to drainage tube removal was (3.0±1.3) d, and length of postoperative hospital stay was (5.3±1.5) d. No significant intraoperative bleeding was noted, and postoperative biliary fistula occurred in one case, which was cured by conservative treatment. No biliary stricture or residual stone was found during follow-up. 
Conclusion: Laparoscopic transcystic duct micro-incision and primary closure is safe and effective in treatment of stone at the junction of the cystic duct and common hepatic duct, which can also effectively avoid stone residual as well as bile duct exploration and T tube drainage. However, it still needs be verified by studies with large sample size.

Abstract:Objective: To investigate the preparation of liposomal sinoporphyrin sodium (DVDMS-L) and its photodynamic killing effect against cholangiocarcinoma cells. 
Methods: The DVDMS-L particles were prepared by thin-film hydration technique, and the particle size and zeta potential, and entrapment efficiency were determined. The cholangiocarcinoma HICC-9810 cells were exposed to the same concentration gradient (0, 0.06, 0.12, 0.25, 0.5 and 1 μmol/L) of DVDMS-L or free sinoporphyrin sodium (DVDMS) under a light dose irradiation of 10 J/cm2 for 4 h, and then, the photodynamic killing effects of DVDMS-L and DVDMS on HICC-9810 cells were determined by CCK8 assay.
Results: Of the prepared DVDMS-L, the average particle size was (113.7±14.2) nm, Zeta potential was – (24.5±3.2) mV, and encapsulation efficiency was (61.74±1.49) %. The viability of HICC-9810 cells was significantly decreased after exposure to either DVDMS-L or DVDMS in a concentration-dependent manner, where the effect of DVDMS-L was significantly greater than that of DVDMS under the same concentration (0.12–
1 μmol/L), with the IC50 of 0.19 and 0.42 μmol/L respectively (all P<0.05).
Conclusion: DVDMS-L is successfully prepared and its photodynamic effect against cholangiocarcinoma cells is superior to that of DVDMS.

Abstract:Objective: To investigate the changes in gene expressions of nuclear receptors (NRs) in hepatic tissue of patients with hereditary cholesterol gallstone (HCGD) of Chinese Han nationality. 
Methods: The blood samples and surgical specimens of hepatic tissue from 9 patients with HCGD (HCGD group), 9 patients with sporadic cholesterol gallstone (SCGD, SCGD group), and 7 hepatic hemangioma patients without gallstone (control group) were collected. The serum levels of lipid metabolism related indicators were determined by enzymatic assay, and mRNA expressions of NRs in liver tissues, which included liver X receptor (LXRα), farnesoid X receptor (FXR), sterol regulatory element binding protein 2 (SREBP2), estrogen receptors α and β (ERα/β), G protein-coupled receptor 30 (GPR30), peroxisome proliferator activated receptor γ (PPARγ), were examined by qRT-PCR.
Results: The serum level of total bile acid (TBA) in HCGD group was significantly reduced compared with control group and SCGD group (both P<0.05), while no significant differences were noted in other lipid metabolism related indicators among the three groups (all P>0.05). Compared with control group, the mRNA expression levels of ERα/β, SREBP2, and PPARγ in HCGD group were significantly increased in HCGD group, and the FXR mRNA expression level was significantly increased in SCGD group (all P<0.05); the mRNA expression levels of LXRα and GPR30 showed no significant differences among the three groups (both P>0.05). in HCGD group, the mRNA expressions of ERα and ERβ were negatively correlated with the serum TBA level (r=–1.000, P=0.000; r=–0.989, P=0.011). 
Conclusion: The genes expressions of ERα/β, SREBP2 and PPARγ are up-regulated in the liver tissue of HCGD patients, which may play important roles in the pathogenesis of HCGD.

Abstract:Objective: To investigate the expression of nucleolar spindle associated protein 1 (Nusap1) in cholangiocarcinoma tissue and its clinical significance.    
Methods: The expressions of Nusap1 mRNA in cholangiocarcinoma and normal bile duct tissue were analyzed by using the GEPIA database tool. The expression levels of Nusap1 protein in 61 paired specimens of cholangiocarcinoma and adjacent tissue were determined by immunohistochemical technique, and the relations of Nusap1 protein expression with clinical parameters and the total survival time of the patients were analyzed. 
Results: The GEPIA database analysis showed that the Nusap1 mRNA was highly expressed in cholangiocarcinoma tissue compared to that in normal bile duct tissue (P<0.05). The results of immunohistochemical staining showed that the expression level of Nusap1 protein was significantly higher than that in the tumor adjacent tissue (47.5% vs. 14.8%, P<0.05). Moreover, the Nusap1 protein expression was significantly associated with the TNM stage (P=0.001), lymph node metastasis (P=0.011), and survival status (P=0.010). Kaplan-Meier analysis showed that the median survival time of patients with positive Nusap1 expression was 23 months and in those with negative Nusap1 expression was 45 months, and the postoperative survival time of the former was significantly shorter than that of the latter (P=0.000). 
Conclusion: Nusap1 expression is increased in cholangiocarcinoma tissue, and it may be closely related to the progression and poor prognosis of cholangiocarcinoma. Nusap1 may potentially become an indicator of prognosis and treatment target for cholangiocarcinoma.

Abstract:Objective: To analyze the expression of glutathione peroxidase 1 (GPX1) in hepatocellular carcinoma (HCC) tissue and its significance by bioinformatics approaches. 
Methods: The expression data of GPX1 in normal lover tissue and HCC tissue were obtained in Ualcan database, the co-expressed genes of GPX1 were retrieved in LinkedOmics, and the biological processes and functions of these genes were determined by GO enrichment analysis and KEGG pathway analysis. Then, the interaction network of the proteins encoded by the relevant genes was analyzed by using STRING. Finally, the relationship between GPX1 expression and the prognosis of the HCC patients was analyzed based on GEPIA database.
Results: Compared with normal liver tissue, the expression levels of GPX1 in HCC tissues from patients with different disease stages (except stage IV) or different ages were significantly increased, further the GPX1 expression levels in HCC tissues from male patients were significantly higher than that from female patients (all P<0.05). The co-expressed genes of GPX1 mainly participated in the biochemical processes such as the transcription and translation of genes, ubiquitination and sulfonylation of proteins, regulation of mRNA stability, and translation of proteasome complex and mitochondria, and were involved in the TGF-β, mTOR, WNT, MAPK, HIF-1α, NF-κB, VEGF and Notch pathways as well as cancer-related pathways. Ten proteins encoded by HCC-related genes were found having interactions with GPX1 encoded protein. The overall survival rates and disease-free survival rates in HCC patients with high GPX1 expression were significantly lower than those in HCC patients with low GPX1 expression (P=0.048, P=0.035).
Conclusion: GPX1 expression is increased in HCC tissue, and its expression is closely related to the occurrence and development as well as prognosis of HCC. So, it can be used as a marker for screening and prognosis estimation of HCC.

Abstract:Objective: To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (TACE) plus portal vein chemotherapy (PVC) for patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).  
Methods: The clinical data of 119 HCC patients associated with PVTT undergoing surgical treatment from January 2010 to January 2016 were retrospectively analyzed. Of the patients, 64 cases underwent placement of an intravenous chemotherapy pump during operation, and then underwent TACE and PVC through the intravenous chemotherapy pump after operation (TACE+PVC group), and 55 cases did not undergo intravenous chemotherapy pump placement and underwent TACE along after operation (TACE group). The postoperative survival and incidence of postoperative complications of the two groups of patients were observed.
Results: In TACE+PVC group and TACE group, the median disease-free survival (DFS) time and median overall survival (OS) time were 13.3 months vs.6.8 months, and 19.5 months vs.12.5 months, and the 0.5-, 1, 2, and 3-year DFS rates were 71.9% vs.52.9%, 57.5% vs. 26.7%, 16.4% vs.8.2% and 6.9% vs. 2.1%, and OS rates were 90.5% vs. 89.1%, 69.5% vs. 50.4%, 37.9% vs. 12.1% and 22.4% vs. 8.1%, respectively. The median tumor-free survival and median survival time in the TACE group were 6.8 months and 12.5 months, respectively. Both DFS rate and OS rate of TACE+PVC group were significantly higher than those of TACE group (P=0.004 and P=0.001). Results of statistical analysis showed that postoperative treatment method was one of the independent risk factors for postoperative survival of the patients (P<0.05). There were no significant differences in incidence of each specific postoperative complication between the two groups (all P>0.05). 
Conclusion: Postoperative adjuvant TACE plus PVC is safe and effective for patients with HCC and PVTT, and its efficacy is superior to that of TACE alone.

Abstract:Objective: To evaluate the safety and effectiveness of using enhanced recovery after surgery (ERAS) protocols during the perioperative period of open liver cancer resection and the influence on postoperative recovery of the patients.
Methods: The randomized controlled trials (RCTs) concerning using ERAS in open liver cancer resection were collected by searching several national and international databases. After the quality assessment and data extraction of the included studies, Meta-analysis was performed by using ReMan5.3 software. 
Results: Sixteen RCTs were finally included, involving 1 770 patients with 888 cases in ERAS group and 882 cases in control group. The results of Meta-analysis showed that in ERAS group compared with control group, the incidence of postoperative complications was significantly reduced (MD=0.47, 95% CI=0.35–0.63, P<0.001); the time to first postoperative gas passage was shortened (SMD=–3.64, 95% CI=–4.72–2.56, P<0.001); the levels of alanine aminotransferase on postoperative day (POD) 3 and 7 (MD=–50.23, 95% CI=–59.35––41.11, P<0.001; MD=–37.48, CI=–42.19––32.78, P<0.001), and the levels of C-reactive protein on POD 1 and 3 (MD=–38.64, 95% CI=–61.14––16.14, P<0.001; MD=–26.75, 95% CI=–46.03––7.47, P<0.01) were all significantly decreased; the length of postoperative hospital stay (MD=–2.71, 95% CI=–3.86––1.55, P<0.001) and total hospital stay (MD=–2.86, 95% CI=–4.11––1.62, P<0.001) as well as the hospitalization cost (MD=–1.20, 95% CI=–1.84–
–0.57, P<0.05) were all significantly reduced.
Conclusion: The implementation of ERAS programs in the perioperative period of open liver cancer resection is safe and effective, can accelerate postoperative recovery, and reduce hospital stay and medical costs of the patients.

Abstract:Objective: To investigate the guiding effect of carbon nanoparticles injection on lymph node clearance during surgery for carcinoma of the ampulla of Vater. 
Methods: Sixty patients with carcinoma of the ampulla of Vater were selected and allocated to observation group and control group, with 30 cases in each group. Patients in observation group underwent injection of 1 mL carbon nanoparticles with 4 points (top, bottom, left and right) into the serosa of the descending duodenum and the capsule of the pancreatic head around the tumor after laparotomy and the operative field exposure, while those in control group underwent saline injection in the same fashion. The number of dissected lymph nodes and other relevant clinical variables were compared between the two groups of patients.
Results: The total number of dissected lymph nodes in observation group was 468, including 416 (88.9%) dark stained lymph nodes. The total number of dissected lymph nodes in control group was 268. The average number of dissected lymph nodes per case in observation group was significantly greater than that in control group (15.23±2.13 vs. 9.77±1.33, P<0.01), which was mainly responsible for the N1 station lymph nodes (P=0.002), and the differences in N2 and N3 dissected lymph nodes showed no significant differences between the two groups (both P>0.05). The operative time, incidence of lymphatic leakage and length of hospital stay showed no significant differences between the two groups (all P>0.05), but the intraoperative blood loss was significantly reduced in observation group compared with control group [(318±30) mL vs. (592±60) mL, P<0.05].
Conclusion: Carbon nanoparticle injection in radical surgery for carcinoma of the ampulla of Vater can increase the number of dissected lymph nodes, reduce intraoperative blood loss, and with no increase of occurrence of complications. It is a safe and effective tracer.

Abstract:Objective: To investigate the implementation of multidisciplinary collaboration led by enterostomal therapists (ET) for risk management of wound treatment and the effect.  
Methods: The data of all patients attending the Center of Wound Care of Xiangya Hospital from May 2013 to April 2017 were collected. The process of multidisciplinary collaboration led by ET for risk management of wound treatment was implemented in patients admitted since May 2015, which included risk assessment, risk analysis, risk identification, and risk decision, and in those regarded as important individuals due to obvious treatment and operative difficulties or potential medical disputes, a series of risk prevention and control measures were performed in partnership with multidisciplinary team. The number, constitution and source of patients as well as patients’ satisfaction rate, and incidence of adverse events were compared before and after implementation of the process.
Results: After implementation, the total number of admitted patients increased by 27.74%, the number of referrals from doctors increased by 54.76%, the number of patients with chronic wounds increased by 51.34%, and the number of ward consultations increased by 52.63% compared with those before implementation. The incidence of adverse events was significantly reduced (0.05% vs. 0.12%, P<0.05) and the patients’ satisfaction rate was significantly increased [(95.36±0.52) % vs. (90.34±0.45) %, P<0.05] after implementation comparted with those before implementation. 
Conclusion: Implementation of multidisciplinary collaboration led by ET for risk management of wound treatment can reduce the incidence of adverse events, increase the patients’ satisfaction rate and improve the wound treatment efficacy. So, it is recommended to be used in clinical practice.

Abstract:Intrahepatic cholangiocarcinoma (ICC) is an epithelial cancer arising above the second-order bile ducts, and is characterized by high tendency to postoperative recurrence, unclear benefit of chemotherapy and low long-term survival rates. At present, there is lack of specific markers for early diagnosis of ICC, so it is always diagnosed at a mid-late or late stage. With the in-depth study of the molecular pathogenesis of ICC, some key regulators such as antioncogenes p53 and p16, proto-oncogenes Ras, and miRNA and histone modifications have been found, which may become the therapeutic targets. Here, the authors address the research progress on the molecular profiling of ICC based on the DNA-RNA-protein central dogma. 

Abstract:After more than 30 years of development, laparoscopic cholecystectomy (LC) has gradually replaced open cholecystectomy (OC) and become the gold standard therapeutic option for the treatment of symptomatic cholecystolithiasis. However, the LC-associated complications, especially bile duct injury (BDI), have generated widespread concern due to the severity of their consequences. Here, the authors address the research progress of BDI in terms of etiology, diagnosis, classification, treatment and prognosis, in order to elaborate the evolutionary characteristics of BDI, with an emphasis on the development of surgical procedures for helping in clinical practice, and establishment of the standardized diagnosis and treatment of BDI.

Abstract:Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in the world. The incidence of HCC has increased significantly over the past decade. Radical treatments such as surgical resection, liver transplantation or radiofrequency ablation are only suitable for less than 30% of cases. Solafenib is the first-line therapy for patients with advanced HCC, but the overall survival rate has not improved significantly and there is also the occurrence of high-frequency adverse events. In recent years, with the deep research in the immune microenvironment of liver tissue, immunotherapy is becoming a new standard for advanced HCC globally. Compared to tyrosine kinase inhibitors (TKIs), immunotherapeutic agents, with higher objective response rates and fewer side effects, may replace sorafenib from standard first-line treatments. The author reviews the current status and progress of immunotherapy for HCC.