Abstract:Intrahepatic cholangiocarcinoma (ICC) is characterized by highly malignant behavior, being difficult to make an early detection, and frequent lymph node metastasis, vascular invasion and intrahepatic dissemination, which lead to the poor prognosis of the patients. At present, radical operation is still the only therapy for providing a chance of long-term survival, but it faces many problems such as low radical-resection rate and high postoperative recurrence rate, as well as many controversies such as determinations for the scope of liver resection and the width of the surgical margin and whether the lymph node dissection should be done. Adjuvant therapy is a critical component of the multimodality treatment, but there are no standard directions and effective protocols for its chemoradiotherapy, and the targeted therapy and immunotherapy are at the stage of exploration. With the development of molecular biological techniques, high degree of heterogeneity has been found in ICC in terms of gene mutation, signal transduction and clinicopathologic features. Here, the authors from the heterogeneity of the biological characteristics and clinical features of ICC in combination with the treatment strategies and the new concept of integrated therapy for ICC, provide new insights and research directions for its individualized treatment.

Abstract:Objective: To compare the efficacy, feasibility and safety of laparoscopic transcystic common bile duct exploration (LTCBDE) and laparoscopic common bile duct exploration (LCBDE) in treatment of common bile duct stones.   
Methods: The relevant studies publicly published from 2009 to 2019 were collected by searching several national and international databases. After literature screening according to the predefined criteria, Meta-analysis was performed by Stata12.0 SE software. 
Results: A total of 21 studies were finally included, involving 3 804 patients with 1 939 cases in LTCBDE group and 1 865 cases in LCBDE group. The results of Meta-analysis showed that the stone clearance rate in LTCBDE group was significantly higher than that in LCBDE group (OR=1.51, 95% CI=1.02–2.25, P=0.038), and the perioperative variables that include intraoperative blood loss (MD=–54.16, 95% CI=–101.07––7.26), operative time (MD=–27.27, 95% CI=–35.20––19.33), postoperative tube retention time (MD=–1.97, 95% CI=–2.32––1.63), length of hospital stay (MD=–3.04, 95% CI=–3.58––2.51) and hospitalization cost (MD=–3 554.99, 95% CI=–4 209.66––2 900.32) in LTCBDE group were all superior to those in LCBDE group (all P<0.05); the incidence rates of postoperative bile leakage (OR=0.28, 95% CI=0.19–0.40), cholangitis (OR=0.33, 
95% CI=0.14–0.80), biliary stricture (OR=0.32, 95% CI=0.11–0.91) and the overall complications (OR=0.33, 95% CI=0.25–0.43) in LTCBDE group were all significantly lower than those in LCBDE group (all P<0.05), and no significant differences were noted in the incidence rates of postoperative pancreatitis (OR=0.56, 95% CI=0.24–1.32) and biliary tract injury or bleeding (OR=0.64, 95% CI=0.24–1.71) between the two groups (both P>0.05).
Conclusion: For common bile duct stones, LTCBDE is safer and more effective than LCBDE. So, it is recommended to be used in clinical practice.

Abstract:Objective: To investigate the efficacy of the sequential therapy of percutaneous transhepatic gallbladder drainage (PTGBD) followed by laparoscopic cholecystectomy (LC) in treatment of acute cholecystitis (AC) and the timing selection. 
Methods: The clinical data of 582 patients with AC treated in the Department of Hepatobiliary Surgery of the Affiliated Hospital of Chengde Medical College from December 2010 to December 2018 were retrospectively analyzed. Of the patients, 456 cases underwent direct LC treatment (LC group) and 126 cases underwent  PTGBD before LC (sequential therapy group). According to the time from onset to operation, the patients were divided into early AC patients (≤7 d) and late AC patients (>7 d). Using propensity score matching method, 115 pairs of patients were selected, which included 62 pairs of early AC patients and 53 pairs of late AC patients. The main clinical variables between LC group and sequential therapy group in early and late AC patients were compared, respectively.
Results: In the early AC patients, the intraoperative blood loss, hospitalization cost and the operative time were reduced compared with those in sequential therapy group (all P<0.05), and no significant differences were noted in terms of open conversion and complication rates between the two group (both P>0.05). In late AC patients, the intraoperative blood loss, operative time and open conversion rate were increased, while the hospitalization cost was decreased in LC group than those in sequential therapy group (all P<0.05), and the incidence rates of complications showed no significant difference between the two groups (P<0.05).
Conclusion: LC alone treatment is superior to that of sequential therapy of PTGBD plus LC in AC patients with the time span from onset to operation ≤7 d, while the sequential treatment of PTGBD plus LC is safe and feasible in those with the time span from onset to operation >7 d. 

Abstract:Objective: To investigate the safety and efficacy of using the self-designed C/S-J type self-releasing biliary stent for biliary drainage after endoscopic retrograde cholangiopancreatography (ERCP). 
Methods: A total of 184 patients with common bile duct stones admitted from October 2015 to October 2018 were allotted to three groups, and underwent ERCP and endoscopic sphincterotomy (EST) plus internal drainage with C/S-J type self-releasing biliary stent (C/S-J group, 104 cases), ERCP and EST plus endoscopic nasobiliary drainage ENBD (ENBD group, 40 cases), and ERCP and EST plus endoscopic retrograde biliary drainage (ERBD) (ERBD group, 40 cases), respectively. The incidence rates of post-ERCP acute pancreatitis (PEP) and acute cholangitis among groups were compared, and the evacuation time of the self-releasing biliary stent in C/S-J group was observed. 
Results: There were no differences in sex, age, stone size, number of stones, previous cholecystectomy and presence or absence of cholangitis among the three groups (all P>0.05). In C/S-J group, ENBD group and ERBD group, the incidence rates of PEP were 6.73% (7/104), 7.50% (3/40) and 10.00% (4/40), and the incidence rates of cholangitis were 0.96% (1/104), 0.00% (0/40) and 2.50% (1/40) respectively, and the differences among groups showed no significance (both P>0.05). In C/S-J group, the stent in two cases was shed and evacuated on the first day after ERCP, the stent in one case failed to evacuate 3 months after ERCP and then was removed with duodenoscope, and the stent in the remaining cases evacuated through the digestive tract within 9–14 d with an average of 10.2 d after ERCP, and no complications such as obstruction, perforation and bleeding of the digestive tract occurred.
Conclusion: Using the self-designed C/S-J type self-releasing biliary stent for post-ERCP biliary drainage is safe and effective, and it also can overcome the limitations of ENBD and ERBD. 

Abstract:Objective: To investigate the effect of age on the occurrence of complicating pancreatitis (PEP) and its severity after endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones.
Methods: The clinical data of 512 patients with common bile duct stones undergoing ERCP from September 2014 to April 2018 were retrospectively analyzed. Of the patients, 232 cases with age equal to or over 75 years were defined as observation group, and 280 cases with age below 75 years were served as control group. The main clinical variables and the incidence as well as the severity of PEP were compared between the two groups of patients.
Results: In observation group, except the proportions of cases with concomitant geriatric conditions (hypertension, diabetes and coronary heart disease) were higher than those in control group (all P<0.05), all other general data showed no significant differences with control group (all P>0.05). There were no significant differences in terms of treatment success rate of ERCP, intraoperative variables and treatment procedures between the two groups of patients (all P>0.05). The incidence rates of postoperative bleeding and hyperamylasemia showed no significant differences between the two groups of patients (both P>0.05). In the entire group, the incidence rate of PEP was 10.94% (56/512), which in observation group was 6.47% (17/232), including 4.74% (11/232) mild, 2.16% (5/232) moderate and 0.43% (1/232) severe PEP; in control group it was 13.93% (39/280), including 8.93% (25/280) mild, 4.29% (12/280) moderate and 0.71% (2/280) severe PEP. The overall incidence rate of PEP in observation group was significantly lower than that in control group (P=0.017), and the incidence rate of each degree of PEP was lower than in control group, but all did not reach a significant difference (P=0.065, 0.180, 0.676). All complications in both groups of patients were alleviated after aggressive conservative treatment.
Conclusion: Atrophy, fibrosis and exocrine hypofunction of the pancreas result from increase in age have a certain inhibitory effect on the occurrence of PEP, but have no obvious influence on the severity of PEP. However, this result still needs to be further assessed by big data from multiple centers.

Abstract:Objective: To investigate the expression of lysyl oxidase-like 2 (LOXL2) in cholangiocarcinoma (CCA) and its association with angiogenesis in CCA.
Methods: The relevant data were downloaded from the GEO database, and then, the difference in LOXL2 mRNA expression between CCA tissue and tumor adjacent tissue was compared; the potential function of the LOXL2 in CCA was determined by gene set enrichment analysis; the relationship between the expressions of LOXL2 and vascular endothelial growth factor A (VEGFA) was analyzed in each dataset. The changes in expression and secretion level of VEGFA in CCA cells after down- or up-regulating LOXL2 expression were detected by Western blot, qRT-PCR and ELISA, respectively. The human umbilical vein endothelial cells (HUVECs) were cultured with the conditioned medium from CCA cells with LOXL2 interference or overexpression, and then, the tube formation abilities of the HUVECs were observed. 
Results: The results of GEO database analyses showed that the LOXL2 expression in CCA tissue was significantly higher than that in tumor adjacent tissue (P<0.05); LOXL2 was possibly associated with angiogenesis in CCA; there was a significant positive correlation between LOXL2 expression and VEGFA expression in each GEO dataset (r=0.320, 0.243, 0.234 and 0.665, all P<0.05). In CCA cells, the VEGFA expression and secretion level of LOXL2 were significantly decreased after LOXL2 interference, and were significantly increased after LOXL2 overexpression (all P<0.05). The number of tube formation was significantly decreased in HUVECs after culture with the conditioned medium from CCA with LOXL2 knockdown, and was significantly increased in HUVECs after culture with the conditioned medium from CCA with LOXL2 overexpression (both P<0.05).
Conclusion: LOXL2 expression is increased in CCA and it may promote angiogenesis in CCA through upregulating VEGFA expression.

Abstract:Objective: To investigate the protein expressions of RCAS1/EBAG9 and P53 in intrahepatic cholangiocarcinoma (ICC) tissue and their clinical significance.
Methods: The protein expressions of RCAS1/EBAG9 and P53 in 41 specimens of ICC tissue and 9 specimens of normal bile duct tissue were detected by immunohistochemcal staining. The relations of RCAS1/EBAG9 and P53 protein expressions with the clinicopathologic characteristics and prognosis of the patients were analyzed.
Results: The positive expression rates of both RCAS1/EBAG9 and P53 proteins in ICC tissue were significantly higher than those in normal bile duct tissue (both P<0.05). The RCAS1/EBAG9 protein expression was significantly related to tumor size, pathological grade, TNM stage and lymph node metastasis, while P53 protein expression was significantly associated with tumor size, pathological grade, and TNM stage (all P<0.05). There was a positive correlation between RCAS1/EBAG9 and P53 protein expression in ICC tissue (r=0.329, P=0.018). The overall postoperative survival time in patients with negative RCAS1/EBAG9 or P53 protein expression was significantly longer than that in patients with positive RCAS1/EBAG9 or P53 protein expression (χ2=3.862, P=0.049; χ2=4.977, P=0.026). Results of univariate and multivariate Cox regression analysis showed that RCAS1/EBAG9 protein expression was an independent risk factor for the prognosis of ICC patients (HR=3.657, 95% CI= 1.111–12.040, P=0.033).
Conclusion: The RCAS1/EBAG9 and P53 protein expressions are increased in ICC tissue, and are closely associated with unfavorable clinicopathologic features and outcomes of the ICC patients, in which, the RCAS1/EBAG9 may probably play a causal role.

Abstract:Objective: To investigate the expression of long non-coding RNA CBR3-AS1 (lncRNA CBR3-AS1) in cholangiocarcinoma (CCA) and its clinical significance. 
Methods: The expressions of lncRNA CBR3-AS1 in CCA tissue and tumor adjacent tissue as well as in CCA cells and normal biliary epithelial cells were determined by qRT-PCR. The relations of lncRNA CBR3-AS1 expression with the clinicopathologic variables and survival rates of the CCA patients were analyzed. The CCA cells were transfected with lncRNA CBR3-AS1 overexpression plasmid (overexpression group), negative control plasmid (control group) and lncRNA CBR3-AS1 silencing sequences (silencing group) respectively, and then, the proliferative and invasion abilities in each group of cells were examined by MTT and Transwell assay.
Results: The lncRNA CBR3-AS1 expression in CCA tissue was significantly higher than that in tumor adjacent tissue, and in CCA cells was significantly higher than that in normal biliary epithelial cells (all P<0.05). The lncRNA CBR3-AS1 expression was significantly associated with the lymph node metastasis, TNM stage and recurrence of the CCA patients (all P<0.05). The overall survival rate in CCA patients with high lncRNA CBR3-AS1 expression was significantly lower than that in those with low lncRNA CBR3-AS1 expression (P=0.004). The lncRNA CBR3-AS1 expression (P=0.020) and TNM stage (P=0.014) were independent risk factors for overall survival rate of the CCA patients. Compared with the CCA cells in control group, the proliferative and invasion abilities were significantly increased in CCA cells in overexpression group, which were significantly reduced in CCA cells in silencing group (all P<0.05).
Conclusion: LncRNA CBR3-AS1 expression is increased in cholangiocarcinoma, which is closely associated with the malignant features of CCA and poor prognosis of the patients. 

Abstract:Objective: To investigate the expressions of TGF-β1, survivin and caspase-3 in hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) tissue and their clinical significance.
Methods: The expressions of TGF-β1, survivin and caspase-3 in intrahepatic bile duct specimens from 52 patients with intrahepatic stones and concomitant ICC (tumor group) and 30 patients with intrahepatic stones and chronic inflammation (inflammation group) as well as 30 specimens of normal intrahepatic bile duct were determined by immunohistochemical staining. The relations of the three factors with the clinicopathologic characteristics and prognosis of ICC patients were analyzed.
Results: In tumor group, inflammation group and normal group, the positive expression rates TGF-β1 and survivin presented a successively decreasing order, while the positive expression rates of caspase-3 showed a successively increasing order (all P<0.05); in ICC tissue, the expressions of TGF-β1 and survivin showed a positive correlation (r=0.917, P<0.01), and both had a negative correlation with that of caspase-3 (r=–0.890, P<0.01; r=–0.894, P<0.01). the results of univariate and multivariate analyses showed that TGF-β1, survivin and caspase-3 were independent influential factors for the prognosis of patients with hepatolithiasis-associated ICC (all P<0.05); the survival rates of patients with positive TGF-β1 or  survivin expression were significantly reduced compared with respective negative ones (χ2=13.192, P=0.001; χ2=10.536, P=0.002), and the survival rate of patients with positive caspase-3 expression was significantly higher than those with its negative expression (χ2=5.469, P=0.023).
Conclusion: The expressions of TGF-β1, survivin and caspase-3 are abnormal in hepatolithiasis-associated ICC tissue, and they may probably be jointly involved in the occurrence and development of this condition.

Abstract:Objective:  To investigate the expression of SUMO-activating enzyme subunit 2 (SAE2) in cholangiocarcinoma tissue and its clinical significance. 
Methods: The expressions of SAE2 in 60 specimens of cholangiocarcinoma tissue and 20 specimens of normal bile duct tissue were detected by immunohistochemical staining. The relations of SAE2 expression with the clinicopathologic factors and prognosis of the patients were analyzed.
Results: The positive SAE2 expression rate in cholangiocarcinoma tissue was significantly higher than that in normal bile duct tissue (71.67% vs. 30.00%, χ2=10.972, P<0.001). The SAE2 expression was significantly associated with the degree of pathological differentiation of the tumor and TNM stage of the patients (both P<0.05). The median survival time of patients with positive SAE2 expression was significantly shorter than that of patients with negative SAE2 expression (13.0 months vs. 30.7 months, χ2=13.805, P<0.001). Results of univariate analysis showed that the SAE2 expression and TNM stage were significantly relevant to the prognosis of the patients (both P<0.001), and the results of Cox multivariate regression analysis identified that the SAE2 expression and TNM stage were independent factors for the prognostic of patients (all P<0.01).
Conclusion: The expression of SAE2 is increased in cholangiocarcinoma tissue, and it is related to the poor prognosis of cholangiocarcinoma patients, suggesting SAE2 expression may be involved in the occurrence and development of cholangiocarcinoma.

Abstract:spectively analyzed. The clinicopathologic characteristics of the patients were summarized. The clinical and pathological factors for lymphatic metastasis of the patients were determined by univariate and multivariate analysis.
Results: Among the 50 patients, the proportion of females was higher than that of males (male to female ratio was 2:3); 7 cases had no symptoms, 43 cases presented with different degrees of upper abdominal pain, nausea/vomiting, tiredness, weight loss and anorexia, and 32 cases (64.0%) had lymphatic metastasis. Results of univariate analysis showed that tumor location, T stage, histological grade, distant metastasis, vascular invasion, hepatic invasion and serum CEA level were significantly associated with lymph node metastasis of the patients (all P<0.05). Results of Logistic multivariate regression analysis showed that tumor location, T stage, histological grade and distant metastasis were independent risk factors for lymphatic metastasis of gallbladder cancer patients (all P<0.05).  
Conclusion: Women account for a relatively high proportion of the patients with gallbladder cancer,  and lymph node metastasis is common. Many factors are closely associated with lymph node metastasis of the patients. In these patients, the lymphatic tissue should be carefully cleared during operation to avoid local recurrence and distant metastasis, and thereby prolong their survival time.

Abstract:Objective: To investigate the application efficacy of the concept of enhanced recovery after surgery (ERAS) in perioperative period of hepatectomy. 
Methods: Ninety-seven patients undergoing liver resection in Fuyang People's Hospital from February 2014 to December 2018 were enrolled, and were randomly allocated to ERAS group (49 cases) and control group (48 cases). Patients in ERAS group received perioperative management directed by ERAS concept, and those in control group underwent perioperative management with a conventional protocol. The main clinical variables were compared between the two groups.
Results: There were no significant differences in general data between the two groups (all P>0.05). In ERAS group compared with control group, the operative time was significantly prolonged [(186.18±51.31) min vs. (157.00±66.53) min, P=0.02], but the intraoperative blood loss and proportion of blood transfusion showed no significant differences (both P>0.05); the time to postoperative tube removal [(6.04±2.09) d vs. (8.44±2.97)d], time to anal gas passage [(1.96±0.79) d vs. (2.52±1.26) d] and length of postoperative hospital stay [(8.57±3.21) d vs. (11.54±4.82) d] were all significantly reduced (all P<0.05); the incidence of postoperative complications was significantly decreased (20.4% vs. 60.4%, P=0.001). 
Conclusion: Using ERAS protocol in perioperative management of hepatectomy in the treatment of liver diseases is safe and effective, and it can also reduce the occurrence of postoperative complications and promote the postoperative recovery of patients. It is recommended to be used in clinical practice.

Abstract:Choledocholithiasis is a common disease of the digestive system. Endoscopic retrograde cholangiopancreatography (ERCP) is an important method for the treatment of common bile duct stones, but postoperative stone recurrence is still a major problem. Many complex factors are involved in the process of the recurrence of the common bile duct stones after removal, which mainly include the history of biliary tract surgery, bile duct dilatation, periampullary diverticulum, biliary infection, etc. Here, the authors address the relevant factors for recurrence of common bile duct stones after ERCP, so as to provide help for its prevention and treatment in clinical practice.

Abstract:Gallbladder carcinoma (GBC) is a rare and highly malignant tumor. Although the continuous deepening of the relevant studies in recent years, the prognosis of patient with GBC is still poor. Surgical treatment offers the only chance of cure for GBC. Multidisciplinary treatment of adjuvant therapy combined with surgery is the hope for advanced GBC patients to improve survival. Here, the authors review and summarize the relevant literature on the treatment of GBC in recent years.

Abstract:Primary aortic mural thrombus is a rare aorta disease. It has an insidious onset, but very dangerous complications that mainly is the lower limb arterial embolism and secondly the visceral arterial embolism, which may result in severe sepsis and multiple organ dysfunction, leading to high mortality rates. Here, the authors address the diagnosis and treatment of the primary aortic mural thrombus in recent years.