Laparoscopic Common Bile Duct Exploration with Gallbladder Preservation: An Innovative Technique for Primary Common Bile Duct Stones.

Background: Primary common bile duct (CBD) stones can be treated with laparoscopic CBD exploration (LCBDE), during which cholecystectomy is routinely performed. For patients without gallstones, we have developed a new procedure, LCBDE with gallbladder preservation. The purpose of this study was to evaluate the management of LCBDE with gallbladder preservation at our institution. Methods: Retrospective analysis the clinical data of 105 patients with primary CBD stones. Demographic data, clinical characteristics, preoperative risk factors, and postoperative complications were evaluated. Results: All patients were divided into two groups depending on the presence of gallstones: the primary CBD stone coexistence gallstones group (Group A, n = 15) and the primary CBD stones absence gallstones group (Group B, n = 90). Complete stones clearance was achieved in all patients. There were no significant differences in postoperative complications rates and mortality between the two groups. The mean postoperative hospital stay was 3.2 days for Group A and 4.1 days for Group B (P = .03). Conclusion: This study found that LCBDE with gallbladder preservation can effectively and safely treat primary CBD stones without gallbladder stones.

MicroRNA-33b regulates hepatocellular carcinoma cell proliferation, apoptosis, and mobility via targeting Fli-1-mediated Notch1 pathway.

MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA-33b (miR-33b) in HCC remains unclear. Here, we found that miR-33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli-1) was a direct target of miR-33b. Overexpression of miR-33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro. Besides, restoration of Fli-1 partially attenuated miR-33b-mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors. Our findings demonstrate the important role of miR-33b/Fli-1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment.

Contrast of therapeutic effects between CBD incision and LLHD stump in biliary tract exploration of LLS for hepatolithiasis.

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) followed by a biliary tract exploration is used to treat left lateral hepatolithiasis. The purpose of this study was to compare the efficacy of two methods of biliary tract explorations in LLSs: biliary tract exploration through a common bile duct (CBD) incision or through the left lateral hepatic duct (LLHD) stump. METHODS: One hundred eight patients were retrospectively analyzed in our hospital from 2009 to 2018. To compare different methods of biliary tract explorations during LLSs, the patients were divided into 2 groups: 36 patients underwent biliary tract exploration through the LLHD stump (LLSS group), and 72 patients underwent biliary tract exploration through the CBD incision (LLSC group). Clinical data on disease characteristics, surgical outcomes, and surgery-related complications were compared between the 2 groups. RESULTS: Bile duct stones were successfully cleared in all patients. For 2 patients in the LLSS group and 3 patients in the LLSC group, treatment was switched to laparotomy. There were no significant differences in the total operation time (P = 0.09), incidence of bleeding volume (P = 0.33), and bile leakage (P = 0.12) between the two groups. The time of choledochoscopy in the LLSS group was significantly lower than that in the LLSC group (P = 0.03). No bile duct injuries, strictures, recurrent stones, or other adverse events were observed in any patients during follow-up. CONCLUSIONS: Exploration of the biliary tract through the LLHD stump is safe and provides satisfactory results for select patients.

miR-186 modulates hepatocellular carcinoma cell proliferation and mobility via targeting MCRS1-mediated Wnt/ß-catenin signaling.

Previous studies have revealed that miR-186 is involved in the pathogenesis of many malignancies. However, the role of miR-186 in hepatocellular carcinoma (HCC) carcinogenesis and its detailed mechanism are poorly understood. This study was to investigate the function of miR-186 in modulating HCC cell proliferation, cell cycle, migration, and invasion. We found that miR-186 was decreased in HCC tissues and cell lines. Loss-of-function experiments showed that reduction of miR-186 dramatically enhanced tumor cell proliferation and metastasis. Besides, miR-186 also participated in the modulation of the cell cycle. In addition, luciferase reporter assays and Western blot analysis showed that MCRS1 was a novel target of miR-186 in HCC cells. Notably, upregulation of miR-186 suppressed the nuclear ß-catenin accumulation and blocked the activation of Wnt/ß-catenin signaling in HCC cells. Forced MCRS1 expression abrogated the inhibitory effect of miR-186 on cell growth, metastasis and Wnt/ß-catenin signaling in HCC cells. Our findings may provide new insight into the pathogenesis of HCC and miR-186/ MCRS1 might function as new therapeutic targets for HCC.

Complication Analysis with Percutaneous Postoperative Choledochoscopy in 826 Patients: A Single-Center Study.

Background: Advances in choledochoscopy technology lead to an improvement in the treatment of hepatolithiasis. The aim of this study is to analyze the complications and efficacy of percutaneous postoperative choledochoscopy (PPOC) for residual stones. Materials and Methods: Retrospective analysis of patients who underwent PPOC for residual stones. Main outcome measures included the rate of stone removal and postoperative complications. Results: Eight hundred twenty-six patients received PPOC. The average duration of choledochoscopy was 30 min (range, 14-42 min). Complications included basket incarceration, T-tube dislodgement, bleeding, bile leaks, and infection. Residual stone clearance rate was achieved in 97% of the cases. Conclusions: PPOC is a safe and effective approach for residual stones.

MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma.

The miR-490-3p was transfected into HepG2 cells to explore the correlation between miR-490-3p and hepatocellular carcinoma cell proliferation, apoptosis, and autophagy and its downstream target gene ATG7. Then we could possibly provide a mechanism for the treatment of hepatocellular carcinoma. MiR-490-3p was screened out by fold change > 4 and P < 0.01 using gene microarray data. The expression level of miR-490-3p was tested by qRT-PCR and the prognosis analysis was achieved by using TCGA data. The cell proliferation was tested via colony formation assay and CCK-8 after the miR-490-3p mimics were transfected into HepG2 cells; the variations of cell cycle and apoptosis was examined by flow cytometry assay; the number of autophagosome was observed by electron microscopy and the changes of autophagy-relative protein LC-II and LC-I as well as their ratio was tested by western blot. MiR-490-3p is low expressed in hepatocellular carcinoma cell lines and tissues. The results of TCGA showed that miR-490-3p high expression indicated better prognosis. After HepG2 cells were transfected with miR-490-3p mimics, cell viability was increased, cell proliferation was enhanced, cell cycle was blocked in G0/G1 phase, cell apoptosis rate was increased, the number of autophagosomes was reduced, autophagy-associated protein LC-II was decreased, and LC-I was increased and their ratio was decreased. After 3-MA was added, cell proliferation was declined, cell apoptosis rate was increased. Besides, the autophagy was inhibited by knocking down the ATG7, which promoted the cell apoptosis. MiR-490-3p could suppress cell proliferation, retard cell cycle and upgrade cell apoptosis by inhibiting autophagy in HCC cells via targeting ATG7. © 2018 IUBMB Life, 70(6):468-478, 2018.

Fli­1 promotes metastasis by regulating MMP2 signaling in hepatocellular carcinoma.

Friend leukemia virus integration 1 (Fli­1) is a newly identified ETS protein, and has critical roles in many malignancies. However, the physiological characters and potential mechanisms of Fli­1 in hepatocellular carcinoma (HCC) progression remains unclear. In the present study, Fli­1 was highly expressed in HCC samples and tumor cell lines. knockdown of Fli­1 with small interfering (si)RNAs significantly reduced the colony formation and metastasis capacity of HCC cell lines in vitro. Subsequent investigation identified that Fli­1 functioned as an oncogene in HCC carcinogenesis and it exerted its promoting metastatic effect primarily by modulating the matrix metalloproteinase (MMP)2 signaling pathway. Collectively, these data provide a novel insight into the mechanism of Fli­1/MMP2 signaling pathway in the pathogenesis of HCC, and Fli­1 may serve as a novel therapeutic target for HCC.

Elevated Preoperative Serum Hs-CRP Level as a Prognostic Factor in Patients Who Underwent Resection for Hepatocellular Carcinoma.

To evaluate the effects of preoperative highly sensitive C-reactive protein (Hs-CRP) in serum on the prognostic outcomes of patients with hepatocellular carcinoma (HCC) following hepatic resection in Chinese samples.From January 2004 to December 2008, a total of 624 consecutive HCC patients who underwent hepatic resection were incorporated. Serum levels of Hs-CRP were tested at preoperation via a collection of venous blood samples. Survival analyses adopted the univariate and multivariate analyses.In our study, among the 624 screened HCC patients, 516 patients were eventually incorporated and completed follow-up. Positive correlations were found regarding preoperative serum Hs-CRP level and tumor size, Child-Pugh class, or tumor stage (all P < 0.0001). Patients with recurrence outcomes and nonsurvivors had increased Hs-CRP levels at preoperation (both P < 0.0001). When compared to the Hs-CRP-normal group, the overall survival (OS) and recurrence-free survival rates were evidently decreased in the Hs-CRP-elevated group. Further, preoperative serum Hs-CRP level might be having possible prediction effect regarding survival and recurrence of HCC patients after hepatic section in the multivariate analysis.Preoperative increased serum Hs-CRP level was an independent prognostic indicator in patients with HCC following hepatic resection in Chinese samples.

TGF-ß1 Reduces miR-29a Expression to Promote Tumorigenicity and Metastasis of Cholangiocarcinoma by Targeting HDAC4.

UNLABELLED: Transforming growth factor ß1 (TGF-ß1) and miRNAs play important roles in cholangiocarcinoma progression. In this study, miR-29a level was found significantly decreased in both cholangiocarcinoma tissues and tumor cell lines. TGF-ß1 reduced miR-29a expression in tumor cell lines. Furthermore, anti-miR-29a reduced the proliferation and metastasis capacity of cholangiocarcinoma cell lines in vitro, overexpression of miR-29a counteracted TGF-ß1-mediated cell growth and metastasis. Subsequent investigation identified HDAC4 is a direct target of miR-29a. In addition, restoration of HDAC4 attenuated miR-29a-mediated inhibition of cell proliferation and metastasis. CONCLUSIONS: TGF-ß1/miR-29a/HDAC4 pathway contributes to the pathogenesis of cholangiocarcinoma and our data provide new therapeutic targets for cholangiocarcinoma.

[Application of three-dimensional visualization technology for laparoscopic resection of cystic carcinoma in the pancreatic body and tail].

OBJECTIVE: To study the application of three-dimensional visualization technology for laparoscopic resection of cystic carcinoma in the pancreatic body and tail. METHODS: Six cases of cystic carcinoma in the pancreatic body and tail treated between Nov, 2009 and Mar, 2011 were retrospectively analyzed. The original image data of 64-slice spiral CT were collected and using adaptive region growing algorithm, the serial CT images were segmented and automatically extracted to obtain the 3-dimensional reconstruction images with customized image manipulation software. The specific surgical approach (the trocar position) and surgical procedure were planned based on the reconstructed mode. RESULTS: The reconstructed 3-dimensional model clearly displayed cystic carcinoma in the pancreatic body and tail and the adjacent organs, showing distinct relationship between the cystoma and the splenic artery and vein. All the patients successfully underwent laparoscopic resection of the pancreatic body and tail without perioperative death. The spleen was preserved in 5 cases and removed in 1 case due to mucinous cystadenocarcinoma. The overall rate of pancreatic fistulae was 33.3% without incidences of postoperative hemorrhage. The average hospital stay of the patients was 12 days. CONCLUSION: Three-dimensional reconstruction based on pancreatic CT data provides valuable assistance for laparoscopic resection of cystic carcinoma in the pancreatic body and tail.

[Expression of miR-216a in pancreatic cancer and its clinical significance].

OBJECTIVE: To explore the clinical significance of miRNA-216a expression in pancreatic cancer. METHODS: Fourteen patients with pancreatic cancer undergoing pancreaticoduodenectomy and 6 patients with benign pancreas lesions were examined for miR-216a expressions in the tumor or lesion tissues using Agilent Human miRNA Microarray (V12.0). The relationship between miR-216a expressions and the clinicopathological features of the patients was analyzed. RESULTS: The expression of miRNA-216a was significantly lower in pancreatic cancer than in benign pancreas lesions (P=0.000). The expression of miRNA-216a was significantly correlated with the T stage of the tumor (P=0.002), but not with the patients' age, gender, smoking status, tumor stage, lymph node metastases, distant metastasis, tumor differentiation, nerve invasion, vessel invasion or serum CA19-9 level (P>0.05). CONCLUSIONS: The down-regulated expression of miR-216a in pancreatic cancer suggests the involvement of miR-216a in the tumorigenesis and development of pancreatic cancer. miR-216a may potentially serve as a novel tumor marker and also a prognostic factor for pancreatic cancer.

[Value of perioperative adjuvant therapy in liver transplantation for advanced hepatocellular carcinoma].

OBJECTIVE: To evaluate the clinical value of perioperative adjuvant chemotherapy in prevention of tumor recurrence and improvement of patient survival after liver transplantation for advanced hepatocellular carcinoma (HCC). METHODS: Twenty patients with advanced HCC (pTNM stages III and IV a) receiving liver transplantation with preoperative transcatheter arterial chemoembolization (TACE) and postoperative adjuvant chemotherapy (ADM+5-Fu+CDDP) were retrospectively reviewed in comparison with 16 patients receiving liver transplantation only for tumor recurrence, cumulative and tumor-free survivals. The feasibility and side-effects of the treatments were also studied. RESULTS: The recurrence rate was lower in the perioperative treatment group than in non-treatment group (12/20, 60.0% vs 11/16, 87.5%, P<0.05). The 1- and 2-year overall survival rates were 70.8% and 47.1% for the chemotherapy group and 43.8% and 20.5% for the non-chemotherapy group respectively, showing significant differences between them (P<0.05). The 1- and 2-year tumor-free survival rates were 60.6%, 40.5% and 33.6%, 15.6% in the two groups, respectively, with also significant differences (P<0.05). CONCLUSIONS: Perioperative adjuvant treatment may significantly decrease the likeliness of tumor recurrence and prolong the survival of patients with advanced HCC after liver transplantation. Chemotherapy with ADM+5-Fu+CDDP can be effective and safe with only mild side-effects.