Background and Aims Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions and mechanisms of dysregulated circRNAs in the cells and EVs of cholangiocarcinoma (CCA). Approach and Results CircRNA microarray was used to identify circRNA expression profiles in CCA tissues and bile‐derived EVs (BEVs). CCA‐associated circRNA 1 (circ‐CCAC1) expression was measured by quantitative real‐time PCR. The clinical importance of circ‐CCAC1 was analyzed by receiver operating characteristic curves, Fisher’s exact test, Kaplan–Meier plots, and Cox regression model. The functions of circ‐CCAC1 and exosomal circ‐CCAC1 were explored in CCA cells and human umbilical vein endothelial cells (HUVECs), respectively. Different animal models were used to verify the in vitro results. RNA sequencing, bioinformatics, RNA immunoprecipitation, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and luciferase reporter assays were used to determine the regulatory networks of circ‐CCAC1 in CCA cells and HUVECs. Circ‐CCAC1 levels were increased in cancerous bile‐resident EVs and tissues. The diagnostic and prognostic values of circ‐CCAC1 were identified in patients with CCA. For CCA cells, circ‐CCAC1 increased cell progression by sponging miR‐514a‐5p to up‐regulate Yin Yang 1 (YY1). Meanwhile, YY1 directly bound to the promoter of calcium modulating ligand to activate its transcription. Moreover, circ‐CCAC1 from CCA‐derived EVs was transferred to endothelial monolayer cells, disrupting endothelial barrier integrity and inducing angiogenesis. Mechanistically, circ‐CCAC1 increased cell leakiness by sequestering enhancer of zeste homolog 2 in the cytoplasm, thus elevating SH3 domain‐containing GRB2‐like protein 2 expression to reduce the levels of intercellular junction proteins. In vivo studies further showed that increased circ‐CCAC1 levels in circulating EVs and cells accelerated both CCA tumorigenesis and metastasis. Conclusions Circ‐CCAC1 plays a vital role in CCA tumorigenesis and metastasis and may be an important biomarker/therapeutic target for CCA.

Background and Objectives:Laparoscopic cholecystectomy (LC) using surgical electrocautery is considered to be the gold standard procedure for the treatment of uncomplicated cholecystitis and cholelithiasis. The objective of the current study was to evaluate the effectiveness and safety of the Harmonic scalpel, an advanced laparoscopic technique associated with less thermal damage in LC, when compared to electrocautery.Methods:From October 2010 through June 2013, a total of 198 patients were randomly allocated to LC with a Harmonic scalpel (experimental group, 117 patients) or conventional monopolar electrocautery (control group, 81 patients). The main outcome measures were operative time, blood loss, conversion to laparotomy, postoperative hospital stay, post-LC pain, and cost effectiveness.Results:The 2 groups were comparable with respect to baseline patient characteristics. When compared to conventional monopolar electrocautery, there were no significant reductions in the operative time, bleeding, frequency of conversion to laparotomy, and duration of postoperative recovery with the Harmonic scalpel (P > .05 for all).Conclusions:Laparoscopic cholecystectomy using conventional monopolar electrocautery is as effective and safe as that with the Harmonic scalpel, for treating uncomplicated cholecystitis and cholelithiasis.

LCBDE and primary CBD closure has excellent short- and long-term outcomes when performed in appropriately selected patients.

AIMTo determine the feasibility, safety, and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) based on favorable or unfavorable location.METHODSOur hospital database included 207 patients who underwent laparoscopic removal of gastric GISTs from January 2004 to September 2015. Patient demographics, clinical presentation, surgery, histopathology, postoperative course, and oncological outcomes were reviewed and analyzed.RESULTSGastric GIST in favorable locations was present in 81/207 (39.1%) cases, and in unfavorable locations in 126/207 (60.9%) cases. Overall mean tumor size was 3.28 ± 1.82 cm. No conversions occurred, and complete R0 resection was achieved in 207 (100%) cases. There were three incidences of iatrogenic tumor rupture. The feasibility and safety of laparoscopic surgery were comparable in both groups with no statistical difference between unfavorable and favorable location groups, respectively: for operative time: 83.86 ± 44.41 vs 80.77 ± 36.46 min, P = 0.627; conversion rate: 0% vs 0%; estimated blood loss: 27.74 ± 45.2 vs 29.59 ± 41.18 mL, P = 0.780; tumor rupture during surgery: 0.90% vs 2.82%, P = 0.322; or postoperative complications: 3.74% vs 7.04%, P = 0.325. The follow-up period recurrence rate was 1.89% with no significant differences between the two groups (3.03% vs 0%, P = 0.447). Overall 5-year survival rate was 98.76% and survival rates were similar between the two groups: 98.99% vs 98.39%, P = 0.623 (unfavorable vs favorable, respectively).CONCLUSIONThe laparoscopic approach for gastric GISTs is safe and feasible with well-accepted oncological surgical outcomes. Strategies for laparoscopic resection should be selected according to the location and size of the tumor. Laparoscopic treatment of gastric GISTs in unfavorable locations should not be restricted in gastrointestinal centers.

Microrchidia family CW-type zinc finger 2 (MORC2) is a ubiquitously expressed protein that contributes to chromatin remodeling, DNA repair, and lipogenesis. However, its role in cholangiocarcinoma (CCA) remains largely unknown. The aim of this study was to investigate the expression profile of MORC2 and its potential functions in CCA progression. The results showed that MORC2 was upregulated in human CCA specimens and cell lines. MORC2 expression was significantly associated with serum CA19-9 levels (P = 0.009), TNM stage (P = 0.003) and lymph node invasion (P = 0.004). Furthermore, high MORC2 expression was associated with poor 5-year survival (P = 0.016). Functional experiments revealed that MORC2 knockdown could suppress CCA cell proliferation, migration, and invasion both in vivo and in vitro . Mechanically, we found that MORC2 promoted CCA cell metastasis through the EMT process and enhanced proliferation via the Akt signaling pathway. Moreover, MORC2 was negatively regulated by miR-186-5p. MiR-186-5p could influence CCA cell proliferation, migration and metastasis by regulating MORC2. Taken together, the findings of this study demonstrated the oncogenic role of MORC2 in CCA tumorigenesis and metastasis, and clarified an underlying regulatory mechanism mediating MORC2 upregulation, which may provide a novel therapeutic target in CCA treatment.