Abstract:Objective: To investigate the clinical effects and outcomes of palliative therapy in treatment of hilar cholangiocarcinoma. Methods: The clinical data of 218 patients with hilar cholangiocarcinoma treated in Xiangya Hospital of Central South University between December 2005 and November 2015 were retrospectively analyzed. Results: Of the 218 patients, 159 cases (72.9%) underwent palliative surgery that included external biliary drainage in 134 cases and internal biliary drainage in 25 cases, and 59 cases (27.1%) underwent interventional treatment that included percutaneous transhepatic biliary drainage (PTBD) in 27 cases and endoscopic retrograde biliary drainage (ERBD) in 32 cases. Two patients died within postoperative 30 d, and the total bilirubin levels were decreased significantly in patients either after palliative surgery or interventional treatment (both P<0.05). Two hundred and two patients were followed up and 196 patients died during this period. The median survival time, and the 1-, 3- and 5-year survival rates were 7 months, and 29.9%, 8.1% and 2.3% in the entire group of patients, which were 7 months, 33.8%, 10.3% and 2.9% in patients undergoing palliative surgery, and 7 months, 14.9%, 0 and 0 in patients undergoing interventional treatment, and the difference between the latter two groups had statistical significance (χ2=5.328, P<0.05). The survival rates between patients undergoing external biliary drainage and internal biliary drainage, or between patients undergoing PTBD and ERBD showed no statistical difference (χ2=0.673; χ2=0.023, both P>0.05). Conclusion: The long-term outcomes of palliative therapy for hilar cholangiocarcinoma are unfavorable. Both palliative surgery and interventional treatment have jaundice reduction effect, and survival rates in patients after palliative surgery are higher than those after interventional treatment, while interventional treatment has the advantages of simple operation and less trauma.

Abstract:Objective: To investigate the application value of three-dimensional reconstruction of CT scan images in diagnosing and the resectability assessment of hilar cholangiocarcinoma. Methods: The clinical data of 15 patients with hilar cholangiocarcinoma treated in the Affiliated Provincial Hospital of Anhui Medical University from January 2015 to December 2016 were retroprospectively studied. Before operation, all patients underwent three-dimensional CT reconstruction, and the locations of the tumors and their relations with the surrounding structures as well as their Bismuth classifications were analyzed and thereafter, the surgical resectabilities of the tumors were judged. Results: Of the 15 patients, all cases underwent surgical exploration; Bismuth classification was type II tumor in one case, type III tumor in 5 cases (type IIIa in 2 cases and IIIb in 3 cases) and type IV tumor in 9 cases respectively; 11 cases underwent radical operation and 4 patients had palliative resection. The diagnostic accuracy of three-dimensional CT reconstruction for tumor classification, and tumor relation with the portal vein and the hepatic artery, and mass volume was 93.3%, 86.7%, 53.3% and 93.3%, respectively. The coincidence rate of preoperative simulation operation and actual operation was 80%. Conclusion: The preoperative three-dimensional CT reconstruction can accurately, directly and dynamically display the hilar cholangiocarcinoma and its three-dimensional relations with adjacent structures, and has high accuracy in judging the resectability of the hilar cholangiocarcinoma. So it is recommended to be used in clinical practice.

Abstract:

Objective: To investigate the impact of extended lymph node dissection on patients with T3 gallbladder cancer. Methods: The clinical data of 45 patients with T3 gallbladder cancer undergoing radical surgery in Taizhou People’s Hospital from January 2009 to December 2014 were retrospectively analyzed. According to the scope of lymphadenectomy, the patients were divided into standard dissection group (20 cases undergoing standard regional lymphadenectomy, namely, dissection of the lymph nodes around the cystic duct and common bile duct and hepatoduodenal ligament), and extended dissection group (25 patients undergoing extended regional lymphadenectomy, namely, standard regional lymphadenectomy plus lymphadenectomy of the posterior superior region of the head of the pancreas, or additional para-aortic lymphadenectomy for those with positive finding in rapid pathological diagnosis). The incidence of postoperative complications and survival conditions of two groups of patients were compared. Results: No perioperative death occurred in any of the groups. The incidence of postoperative complications was 15% (3/20) in standard dissection group and 20% (5/25) in extended dissection group, which showed no statistical difference (P>0.05). The 1- and 3-year cumulative survival rate and median survival time was 8%, 0 and 9 months in standard dissection group, and 100%, 44% and 28 months in extended dissection group, and the survival rate in extended dissection group was significantly higher than that in standard dissection group (χ2=45.921, P<0.05). Conclusion: The extended regional lymphadenectomy focusing on lymph nodes in the posterior superior region of the head of the pancreas and para-aortic lymph nodes may effectively improve the survival of the patients with T3 gallbladder cancer without an increase of surgical complications under the premise of radical resection of the primary lesion.

Abstract:Objective: To investigate Maspin protein expression in cholangiocarinoma tissue as well as its clinical significance and relation with p53 protein. Methods: The Maspin and p53 protein expressions in 42 specimens of cholangiocarinoma tissues along with their adjacent tissues and 12 specimens of normal biliary duct tissues were detected by immunohistochemcal staining. The relations of the two proteins with clinicopathologic factors and prognosis of the patients and the relationship between the two proteins were analyzed. Results: The positive expression rates of both Maspin and p53 proteins in cholangiocarinoma tissue were significantly higher than those in cancer adjacent tissue and normal bile duct tissue (all P<0.05); the Maspin protein expression was significantly related to lymph node metastasis and distant metastasis of cholangiocarinoma, while p53 protein expression was significantly associated with the pathological grade, TNM stage, lymph node metastasis and distant metastasis of cholangiocarinoma, but there was no significant correlation between Maspin and p53 protein expression in cholangiocarinoma tissue (r=–0.329, P=0.144). The postoperative survival time in patients with positive Maspin expression was significantly longer than those with negative Maspin expression (χ2=4.440, P=0.035), while in patients with positive p53 expression was significantly shorter than those with negative p53 expression (χ2=8.231, P=0.004). Results of univariate and multivariate Cox regression analysis showed that Maspin protein expression was an independent prognostic index for holangiocarcinoma patients (HR=0.094, 95% CI=0.015–0.593, P=0.012). Conclusion: The Maspin protein expression is increased in cholangiocarcinoma tissue, but its deficiency or absence may closely be related to unfavorable clinicopathologic features and outcomes of the patients, and the mechanism of its action may not be associated with p53 protein.

Abstract:Objective: To investigate the effect of RNA-mediated interference of inducible nitric oxide synthase (iNOS) gene expression on growth of human cholangiocarcinoma cells. Methods: Three iNOS-siRNA sequences targeting iNOS gene (siRNA1, siRNA2 and siRNA3) and a negative control siRNA sequence were designed and synthesized, and were respectively transfected into human cholangiocarcinoma QBC939 cells, and then, the transfection efficiencies were determined by fluorescence microscopic observation, and the interference effects were examined through changes in iNOS mRNA and protein expressions. The iNOS-siRNA sequence with most evident interference efficacy was selected for use to observe the changes in proliferation, cell cycle and apoptosis in QBC939 cells after its transfection. The untreated QBC939 cells served as blank control. Results: All the three synthesized iNOS-siRNA sequences were effectively transfected into QBC939 cells, and iNOS mRNA and protein expression levels were all significantly reduced in QBC939 cells after their transfection (all P<0.05), in which, siRNA2 showed the most evident inhibitory effect on iNOS. The negative control siRNA sequence exerted no significant effect on iNOS mRNA and protein expressions in QBC939 cells (both P>0.05). In QBC939 cells after siRNA2 transfection, the proliferation was significantly decreased, with significant G0/G1 phase arrest and increased apoptosis rate (all P<0.05), while no significant changes were noted in above indexes in QBC939 cells after transfection of negative control siRNA sequence (all P>0.05). Conclusion: RNA interference can effectively decrease iNOS gene expression in cholangiocarcinoma cells, which thereby inhibit the proliferation and promote apoptosis of cholangiocarcinoma cells.

Abstract:Objective: To investigate the influence of interleukin 13 (IL-13) on activity of transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in bile duct fibroblasts and the interventional effect of dexamethasone (Dex). Methods: Rabbit bile duct fibroblasts were isolated and cultured and then identified. Then, the bile duct fibroblasts were exposed to IL-13 or IL-13 plus different concentrations (0.01, 0.05 and 0.25 mg/mL) of Dex respectively for 48 h, using untreated bile duct fibroblasts as blank control. Afterwards, cell proliferation was assessed by CCK-8, the mRNA expressions of TGF-β1, Smad3 and Smad4 were determined by real-time PCR and the protein expressions of TGF-β1 and Smad4 were examined by Western blot. Results: In bile duct fibroblasts after exposure to IL-13 for 48 h, the cell proliferation was significantly increased, the mRNA expressions of TGF-β1, Smad3 and Smad4 and the protein expressions of TGF-β1 and Smad4 were significantly up-regulated (all P<0.05), and the above changes exerted by IL-13 were significantly inhibited by Dex addition in a certain concentration-dependent manner (part P<0.05). Conclusion: IL-13 can enhance the activity of TGF-β1/Smads pathway in bile duct fibroblasts, and weakening the activation of this signaling pathway may be one of the mechanisms of the inhibitory effect of Dex on benign biliary stricture.

Abstract:Objective: To investigate the enhancing effect of quercetin (QUE) on sensitivity of endocrine-resistant breast cancer to tamoxifen (TAM) therapy. Methods: The TAM-resistant breast cancer cell lines (MCF-7/TAM-R) were induced by high dose TAM pulse exposure, and then were transplanted into nude mice. After that, the tumor xenograft-bearing nude mice were randomly divided into 4 groups, and were administrated with vehicles (control group), QUE 50 mg/kg once every 2 days (QUE group), TAM 5 mg/kg once daily (TAM group) or QUE 50 mg/kg once every 2 days plus TAM 5 mg/kg once per day (QUE+TAM group), respectively. The general conditions of the tumor-bearing mice and the volume changes of the tumors were monitored, and the mice in each group were sacrificed at 21th day after treatment, and then the tumor weight and the expressions of ERα, HER-2, pMAPK, MAPK, pAkt and Akt in the tumor tissue were determined. Results: During treatment, the daily food intake and body weight were significantly reduced in mice of QUE+TAM group and QUE group, but showed no abnormalities in mice of control group and TAM group; the tumor growth started to decrease from the 12th day, and decreased significantly to the 21th day in QUE+TAM group (P<0.05), while the tumors grew continuously in other groups. Compared with control group, the tumor weight was significantly decreased in QUE+TAM group (P<0.05), but showed no significant difference in the other two groups (both P>0.05); the ERα protein expression was increased while HER-2, pMAPK and pAkt protein expressions were decreased markedly in the tumor tissues of QUE+TAM group and QUE group, but the expressions of all above proteins showed no obvious change in TAM control, while the expressions of unphosphorylated MAPK and Akt showed no remarkable changes in any of the groups. Conclusion: QUE can restore the sensitivity of endocrine-resistant breast cancer to TAM, which may probably be associated with its down-regulating HER-2 and downstream pMAPK and pAkt expressions, and up-regulating ERα expression; QUE has potential toxicity and adverse activities, so its safe dose range and minimum effective dose should be determined.

Abstract:Objective: To investigate the efficacy of liver resection based on pedicles of hepatic segments in treatment of hepatolithiasis. Methods: Using a prospective, cohort-controlled design, 90 patients with hepatolithiasis were randomly designated to study group and control group, with 45 cases in each group. Patients in study group underwent hepatectomy based on pedicles of hepatic segments and those in control group underwent hepatectomy based on Couinaud’s liver segment classification under ultrasound positioning. The main clinical variables between the two groups of patients were compared. Results: The general condition, liver function, stone distribution, bile duct variations and scope of liver resection showed no statistical difference between the two groups of patients before operation (all P>0.05). The intraoperative blood loss, incidence of postoperative complications, drainage volume and residual stone rate were significantly reduced in study group compared with control group (all P<0.05). The differences in operative time, blood transfusion rate, postoperative liver function, time to postoperative gas passage, and length of postoperative hospital stay showed no statistical significance (all P>0.05). Conclusion: Hepatectomy based on pedicles of hepatic segments has the advantages of small amount of blood loss and exudation as well as low rate of complications and residual stones, so it suitable to be used in treatment of hepatolithiasis.

Abstract:Objective: To evaluate the safety and efficacy of minimally invasive hepatectomy for hepatolithiasis. Methods: Literature regarding studies comparing minimally invasive hepatectomy and open hepatectomy for hepatolithiasis was collected through searching several national and international online databases. After data extraction, Meta-analysis was performed by using Stata 12.0 software. Results: Twenty-four studies were finally included involving 2 051 patients, of whom, 993 cases underwent minimally invasive hepatectomy and 1 058 cases underwent open hepatectomy. Results of Meta-analysis showed that minimally invasive hepatectomy had significantly reduced intraoperative blood loss (SMD=–0.867, 95% CI=–1.261––0.472, P<0.001), blood transfusion rate (OR=0.475, 95% CI=0.330–0.683, P<0.001), incidence of postoperative complications (OR=0.493, 95% CI=0.382–0.638, P<0.001), postoperative fasting time (SMD=–1.845, 95% CI=–2.609––1.082, P<0.001), length of postoperative hospital stay (SMD=–0.983, 95% CI=–1.323––0.643, P<0.001) and stone recurrence rate (OR=0.513, 95% CI=0.322–0.816, P=0.005) compared with open hepatectomy, while no significant differences were noted in operative time, initial stone clearance rate and final stone clearance rate between the two approaches (all P>0.05). Conclusion: Minimally invasive hepatectomy is a safe and effective approach for hepatolithiasis, and is superior to open hepatectomy in most intra- and postoperative variables. However, more randomized controlled trials are still needed to verify these differences.

Abstract:Objective: To compare the efficacy and safety of laparoscopic cholecystectomy (LC) in treatment of acute calculous cholecystitis (ACC) at different timing within early stage. Methods: The literature of clinical studies comparing the efficacy and safety of LC at different timings for ACC publically published before April 2017 was searched from national and international databases. Meta-analysis was performed on some relevant clinical variables by using RevMan 5.3 software. Results: Fifteen studies were included, involving 16 389 patients, of whom, 13 417 cases underwent LC within 48 h after onset and 2 972 cases underwent LC within 48 to 72 h after onset. The results of Meta-analysis showed that, the operative time (MD=–11.33, 95% CI=–17.26––5.40, P=0.0002), intraoperative blood loss (MD=–24.60, 95% CI=–45.83––3.36, P=0.02), incidence of bile duct injury (OR=0.48, 95% CI=0.26 0.90, P=0.02) and open conversion rate (OR=0.56, 95% CI=0.43–0.74, P<0.0001) were reduced in patients undergoing LC within 48 h compared with those undergoing LC within 48 to 72 h. The differences in the length of hospital stay, overall incidence of complications and the incidence of bile leakage, intestinal obstruction, postoperative intra-abdominal hemorrhage, wound infection, abdominal infection, pulmonary infection and incisional hernia showed no statistical significance between the two groups of patients (all P>0.05). Conclusion: In ACC patients, LC has better efficacy and safety when performing within 48 h after onset.

Abstract:Objective: To investigate the safety and effectiveness of laparoscopic common bile duct exploration (LCBDE) with primary closure in treatment of choledocholithiasis in elderly patients. Methods: The clinical and follow-up data of 146 patients with gallbladder stones and concomitant choledocholithiasis undergoing LCBDE with primary closure from December 2012 to December 2016 were retrospectively analyzed. The patients were divided into two groups according to their age, with 61 cases ≥65 years old in elderly group and 85 cases <65 years old in non-elderly group. The main clinical variables between the two groups of patients were compared. Results: LCBDE with primary closure was uneventfully completed in all the 146 patients, without any open conversion. In elderly group versus non-elderly group, the operative time (90.98 min vs. 93.12 min), intraoperative blood loss (25.08 mL vs. 24.94 mL) and number of stones in the common bile duct (2.36 vs. 1.98) showed no statistical difference (all P>0.05), but the postoperative drainage time (4.74 d vs. 4.13 d), time to ambulation (1.87 d vs. 1.61 d), time for bowel function recovery (2.43 d vs. 2.05 d) and length of hospital stay (7.46 d vs. 6.62 d) were significantly prolonged (all P<0.05). No serious complications occurred in either of the groups, and no significant differences were noted in incidence of bile leakage (9.8% vs. 9.4%), abdominal bleeding (1.6% vs. 2.4%), residual stone rate (1.6% vs. 1.2%) and stone recurrence rates (1.6% vs. 0) between the two groups (all P>0.05). Conclusion: LCBDE with primary closure is safe and effective in treatment of choledocholithiasis in elderly patients, and can be used as a preferable surgical procedure for elderly patients with choledocholithiasis under adherence to strict surgical indications.

Abstract:Objective: To investigate the influential factors for hypercoagulable state formation in patients after laparoscopic cholecystectomy. Methods: One hundred and eight patients undergoing laparoscopic cholecystectomy from January 2012 to December 2015 were prospectively selected as study subjects. The differences in the relevant clinical variables were compared between patients with and without hypercoagulable state formation, and the factors for postoperative hypercoagulable state formation were analyzed. Results: Of the 108 patients undergoing laparoscopic cholecystectomy, 32 cases (29.63%) were found having a hypercoagulable state. In patients with hypercoagulable state compared with those without hypercoagulable state, the proportion of cases with hyperlipidemia history and preoperative levels of systolic blood pressure, fibrinogen (Fbg), D-dimer (D-D), platelet count (PLT), prothrombin fragments (F1+F2), transferrin (Trf), alpha acid glycoprotein (Orso), C-reactive protein (CRP), interleukin 6 (IL-6), and low density lipoprotein cholesterol (LDL-C) were significantly increased, while the high density lipoprotein cholesterol (HDL-C) level was significantly decreased (all P<0.05). Univariate and multivariate Logistic regression analyses showed that hyperlipidemia history, Fbg≥3.95g/L, D-D≥100.00 μg/L, PLT≥228.00×109/L, F1+F2≥0.16 nmol/L, Trf≥2.15 g/L, Orso≥0.85 g/L, CRP≥1.50 mg/L, IL-6≥1.50 pg/mL, LDL-C≥2.85 mg/dL were independent risk factors for hypercoagulable state formation after laparoscopic cholecystectomy (all P<0.05). Conclusion: For patients undergoing laparoscopic cholecystectomy, attention should be paid to the occurrence of hypercoagulable state formation in those with above risk factors.

Abstract:Objective: To investigate the feasibility and efficacy of laparoscopic first stage and open second stage ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) in treatment of huge hepatocellular carcinoma (HCC). Methods: The clinical data of 12 patients with huge HCC with concomitant liver cirrhosis undergoing laparoscopic first stage and open second stage ALPPS from April 2014 to April 2016 were retrospectively analyzed. Results: Before treatment, all patients were classified as Child B liver function, the average ICGR15 was (23.4±1.5)%, and the estimated future liver remnant (FLR) was (308±64) mL with a ratio of (27±3.8)% to the total estimated liver volume. In the first-stage operation, except one case of open conversion, laparoscopic procedure was successfully performed in all remaining cases; after the first-stage operation, the liver function transferred to Child A in all patients, the average ICGR15 was (8.6±4.2)%, and FLR was (684±129) mL with a ratio of (56±7.7)% to the total estimated liver volume. The average time interval between the first- and second-stage operations was 10.5 (7–16) d. in the open second-stage operation, 7 patients underwent extended right hemihepatectomy and 5 patients underwent right hepatic trisegmentectomy, with an average intraoperative blood loss of 650 (200– 1 200) mL and blood transfusion of 3.5 (1.5–6) U respectively. No severe postoperative complications occurred, and the ascites and transient bile leakage were resolved by conservative treatments. Postoperative follow-up was conducted for 6 to 30 months, during which time, 3 patients died and the remaining patients were alive. Conclusion: Laparoscopic first stage and open second stage ALPPS is a safe and effective treatment method for huge HCC.

Abstract:Due to complex causes and difficult surgical procedures as well as residue and relapse prone, the treatment of complex biliary stones has always been a thorny problem in hepatobiliary surgical practice. Although the traditional surgical procedure offers demonstrable efficacy, it has shortcomings such as severe surgical trauma that will cause slow recovery and numerous postoperative complications of the patients. With the development and popularization of endoscopic techniques in recent years, minimally invasive approaches have become increasingly prevalent in treatment of complex biliary stones by advantages such as minor trauma and quick recovery. Here, the authors address the progress of minimally invasive treatment of complex biliary stones, to be used for clinical reference .

Abstract:

The reasons for pigment gallstone formation are currently regarded as being related to the sedimentation of bile sludge plus other factors such as deconjugation of the conjugated bilirubin by exogenous β-glucuronidase produced by bacteria in biliary tract. Moreover, many investigations demonstrated that the source of biliary bacteria is closely related to duodeno-biliary reflux due to sphincter of Oddi relaxation. The authors overview the current research status and the relevant investigations and combine them with the authors’ own related studies and reflections to discuss the relationship between duodeno-biliary reflux and pigment gallstone formation.

Abstract:Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a new approach for two-stage hepatectomy procedure developed in recent years. The major advantages of ALPPS are offering rapid hypertrophy of the future liver remnant (FLR), and higher rates of the completion of the second-stage procedure and R0 resection compared to the traditional two-stage hepatectomies, which give hope to patients with liver malignancies considered unresectable due to an insufficient FLR. In this paper, the authors address the research progress on the mechanisms of ALPPS causing rapid FLR hypertrophy and relevant factors.