Exosomal lncRNA HEIH, an essential communicator for hepatocellular carcinoma cells and macrophage M2 polarization through the miR-98-5p/STAT3 axis.

Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment.

[Vascular endothelial growth factor receptor-1 activation induces epithelial to mesenchmal transition in hepatocellular carcinoma cell line MHCC97-H.].

OBJECTIVE: To evaluate the mechanism of increased invasion and migration of hepatocellular carcinoma (HCC) cells induced by vascular endothelial growth factor receptor-1 (VEGFR-1) activation. METHODS: Vascular endothelial growth factor-B (VEGF-B) was used to induce and stimulate hepatocellular carcinoma cell line MHCC97-H. Morphologic changes of MHCC97-H were investigated. The expression of E-cadherin and alpha-catenin (two epithelial markers) and Vimentin and N-cadherin (two mesenchymal markers) was detected by reverse transcriptase polymerase chain reaction (RT- PCR), western blotting, and immunofluorescence staining. Cell invasion and migration test was performed. RESULTS: Treatment of MHCC97-H cells with VEGF-B led to morphologic changes characteristic of epithelial to mesenchymal transition (EMT), including loss of polarity, increased intercellular separation, and the presence of pseudopodia. Expression of the epithelial adhesion molecules, including E-cadherin and alpha-catenin, was decreased after VEGF-B treatment. Conversely, an increase in the expression of the mesenchymal cell markers, including N-cadherin and vimentin, was observed after VEGF-B treatment (P less than 0.05). VEGF-B-treated cells exhibited a change in E-cadherin from an organized, membrane-bound structure to a disorganized state in which it was noted to be dispersed throughout the cytoplasm. Pretreatment with VEGFR-1 blocking antibody 18F1 inhibited the change in localization of E-cadherin induced by VEGF-B treatment. The ability of invasion and migration of MHCC97-H was enhanced by VEGF-B reatment (P less alpha 0.05). CONCLUSION: Increased invasion and migration of HCC cells induced by VEGFR-1 activation was mediated by epithelial to mesenchymal transition.

Mini-invasive vs open resection of colorectal cancer and liver metastases: A meta-analysis.

BACKGROUND: The safety and feasibility of the simultaneous resection of primary colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM) have been demonstrated in some studies. Combined resection is expected to be the optimal strategy for patients with CRC and SCRLM. However, traditional laparotomy is traumatic, and the treatment outcome of minimally invasive surgery (MIS) is still obscure. AIM: To compare the treatment outcomes of MIS and open surgery (OS) for the simultaneous resection of CRC and SCRLM. METHODS: A systematic search through December 22, 2018 was conducted in electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library). All studies comparing the clinical outcomes of MIS and OS for patients with CRC and SCRLM were included by eligibility criteria. The meta-analysis was performed using Review Manager Software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by a funnel plot and the Begg's and Egger's tests. Fixed- and random-effects models were applied according to heterogeneity. RESULTS: Ten retrospective cohort studies involving 502 patients (216 patients in the MIS group and 286 patients in the OS group) were included in this study. MIS was associated with less intraoperative blood loss [weighted mean difference (WMD) = -130.09, 95% confidence interval (CI): -210.95 to -49.23, P = 0.002] and blood transfusion [odds ratio (OR) = 0.53, 95%CI: 0.29 to 0.95, P = 0.03], faster recovery of intestinal function (WMD = -0.88 d, 95%CI: -1.58 to -0.19, P = 0.01) and diet (WMD = -1.54 d, 95%CI: -2.30 to -0.78, P < 0.0001), shorter length of postoperative hospital stay (WMD = -4.06 d, 95%CI: -5.95 to -2.18, P < 0.0001), and lower rates of surgical complications (OR = 0.60, 95%CI: 0.37 to 0.99, P = 0.04). However, the operation time, rates and severity of overall complications, and rates of general complications showed no significant differences between the MIS and OS groups. Moreover, the overall survival and disease-free survival after MIS were equivalent to those after OS. CONCLUSION: Considering the studies included in this meta-analysis, MIS is a safe and effective alternative technique for the simultaneous resection of CRC and SCRLM. Compared with OS, MIS has less intraoperative blood loss and blood transfusion and quicker postoperative recovery. Furthermore, the two groups show equivalent long-term outcomes.

Effectiveness and safety of robotic versus traditional laparoscopic gastrectomy for gastric cancer: An updated systematic review and meta-analysis.

Gastrectomy is considered the gold standard treatment for gastric cancer patients. Currently, there are two minimally invasive surgical methods to choose from, robotic gastrectomy (RG) and laparoscopic gastrectomy (LG). Nevertheless, it is still unclear which is superior between the two. This meta-analysis aimed to investigate the effectiveness and safety of RG and LG for gastric cancer. A systematic literature search was performed using PubMed, Embase, and the Cochrane Library databases until September 2018 in studies that compared RG and LG in gastric cancer patients. Operative and postoperative outcomes analyzed were assessed. The quality of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluations. Twenty-four English studies were analyzed. The meta-analysis revealed that the RG group had a significantly longer operation time, lower intraoperative blood loss, and higher perioperative costs compared to the LG group. However, there were no differences in complications, conversion rate, reoperation rate, mortality, number of lymph nodes harvested, days of first flatus, postoperative hospitalization time, and survival rate between the two groups. RG was shown to be associated with decreased intraoperative blood loss and increased perioperative cost and operation time compared to LG. Several higher-quality original studies and prospective clinical trials are required to confirm the advantages of RG.

Risk factors for 30-day unplanned reoperation after pancreatoduodenectomy: A single-center experience.

OBJECTIVE: The purpose of this study was to investigate the rate and reasons and also the risk factors for unplanned reoperation after pancreatoduodenectomy (PD) in a single center. PATIENTS AND METHODS: This retrospective analysis included patients who underwent PD in the First Affiliated Hospital of Nanchang University between January 2010 and January 2018. The patients were divided into nonreoperation and reoperation groups according to whether they underwent unplanned reoperation following the primary PD. The incidence and reasons were examined. In addition, multivariate logistic regression analysis was performed to identify the risk factors for unplanned reoperation. RESULTS: Of the 330 patients who underwent PD operations, 22 (6.67%) underwent unplanned reoperation. The main reasons for reoperation were postpancreaticoduodenectomy hemorrhage (PPH) (12/22 [54.5%]) and pancreaticoenteric anastomotic (PEA) leak (5/22 [22.7%]). Multivariate logistic regression analyses identified that diabetes (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.06-12.90; P = 0.04), intraoperative blood loss ≥400 mL (OR, 4.06; 95% CI, 1.29-12.84; P = 0.02), occurrence of postoperative complications in the form of PPH (OR, 30.67; 95% CI, 8.85-106.31; P < 0.001), and PEA leak (OR, 11.53; 95% CI, 3.03-43.98, P < 0.001) were independent risk factors for unplanned reoperation. CONCLUSIONS: Our results suggest that diabetes, intraoperative blood loss ≥400 mL, PPH, and PEA leak were independent risk factors for unplanned reoperation after primary PD.

[The expression and significance of vascular endothelial growth factor and its receptors in hepatocellular carcinoma cell lines with various metastatic potentialities].

OBJECTIVES: To examine whether or not vascular endothelial growth factor (VEGF) and its receptors were expressed in hepatocellular carcinoma cell lines with various metastatic potentialities. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA) and Western blot were employed to study the expressions of VEGFR-1, VEGFR-2, VEGF-A and VEGF-B in four hepatocellular carcinoma cell lines MHCC97-H, MHCC97-L, SMMC7721 and HepG-2 and one normal liver cell line L-02. RESULTS: Three hepatocellular carcinoma cell lines (MHCC97-H, MHCC97-L, SMMC7721) expressed VEGFR-1 mRNA and their proteins. The expression level of VEGFR-1 in MHCC97-H was higher than that in MHCC97-L (P less than 0.05) and the expression level of VEGFR-1 in MHCC97-L was higher than that in SMMC7721 (P less than 0.05). No expression of VEGFR-1 was found in HepG-2 or L-02. All four hepatocellular carcinoma cell lines and the L-02 cell line expressed VEGFR-2 mRNA and the protein, as well as the VEGFR-1 ligands VEGF-A and VEGF-B. The expression level of VEGFR-2 in all tested hepatocellular carcinoma cell lines and normal liver cell line L-02 showed no significant differences (P more than 0.05). CONCLUSION: VEGFR-1 was expressed in 4 hepatocellular carcinoma cell lines with various metastatic potentialities. The expression levels appeared to be positively correlated with the potentialities of metastasis of the hepatocellular carcinoma cell lines. VEGFR-1 may relate to the invasiveness and metastatic potential of the hepatocellular carcinoma.

Feasibility and safety of laparoscopic liver resection for hepatocellular carcinoma with a tumor size of 5-10 cm.

BACKGROUND: Although laparoscopic liver resection has developed rapidly and gained widespread acceptance for the treatment of benign liver diseases and hepatocellular carcinoma with a small tumor size, its usefulness for the treatment of large tumors is less clear, due to concerns about compromising oncological principles and patient safety. The purpose of this study was to explore the safety and feasibility of laparoscopic liver resection for the treatment of hepatocellular carcinoma with a tumor size of 5-10 cm. METHODS: From March 2007 to December 2011, we performed liver resection in 275 patients with hepatocellular carcinoma with a tumor size of 5-10 cm. Laparoscopic liver resection was performed in 97 patients (Lap-Hx group) and open liver resection was performed in 178 patients (Open-Hx group). Operative time, estimated intraoperative blood loss, blood transfusion rate, and length of postoperative hospital stay were compared between the two groups. Early and intermediate-term postoperative outcomes were also compared. RESULTS: Only one liver resection was performed for every patient with HCC in the present study.No operative deaths occurred in either group. Nine of the laparoscopic procedures were converted to open resection (conversion rate 9.28%). There were no significant differences in mean operative time (245±105 min vs 225±112 min; P = .469), mean estimated intraoperative blood loss (460±426 mL vs 454±365 mL; P = .913), or blood transfusion rate (4.6%, 4/88) vs (2.8%, 5/178)(P = .480) between the Lap-Hx and Open-Hx groups. However, postoperative hospital stay was shorter in the Lap-Hx group than the Open-Hx group (8.2±3.6 days vs 13.5±3.8 days; P = .028). There was a lower rate of postoperative complications in the Lap-Hx group than the Open-Hx group (9% vs 30%; P = .001), but there were no severe complications in either group. The median overall follow-up time was 21 months (range 2-50 months) and the median follow-up of time of survivors was 23 months. The median follow-up time was 25 months in the Lap-Hx group and 20 months in the Open-Hx group. The follow-up rate was 95% (84 patients) in the Lap-Hx group and 95% (169 patients) in the Open-Hx group, which was not a significant difference between the two groups (P = .20). Tumor recurrence occurred in 17 patients (20%) in the Lap-Hx group and 35 patients (21%) in the Open-Hx group, which was not a significant difference between the two groups (P = .876). A total of 33 patients (13%) died during the study period, including 12 patients (14%) in the Lap-Hx group and 21 patients (12%) in the Open-Hx group, which was not a significant difference between the two groups (P = .695). There were also no significant differences in the 1-year rates of overall survival (94% vs 95%; P = .942) or disease-free survival (93% vs 92%; P = .941), or the 3-year rates of overall survival (86% vs 88%; P = .879) or disease-free survival (66% vs 67%; P = .931), between the Lap-Hx and Open-Hx groups. CONCLUSIONS: Laparoscopic liver resection is safe and feasible in patients with hepatocellular carcinoma with a tumor size of 5-10 cm. Laparoscopic liver resection can avoid some of the disadvantages of open resection, and is beneficial in selected patients based on preoperative liver function, tumor size and location.