ZEB2 promotes tumor metastasis and correlates with poor prognosis of human colorectal cancer.

Colorectal cancer remains the most common cause of cancer-related deaths worldwide and it continues to lack an effective treatment. Here, we found that zinc finger E-box binding homeobox 2 (ZEB2) was overexpressed in several colorectal cancer cell lines and colorectal cancer specimens relative to adjacent non-cancerous tissues. Although ZEB2 has been reported to be associated with several tumors, its involvement in colorectal cancer progression remains unclear. In this study, we investigated the biological functions and molecular mechanisms of ZEB2 underlying colorectal carcinoma metastasis and angiogenesis. HCT116 colorectal cancer cells were treated with ZEB2 shRNA or recombinant ZEB2, and the expression of ZEB2 was assessed using reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting, respectively. Ectopic expression of ZEB2 induced proliferation and epithelial-mesenchymal transition (EMT), and increased the metastatic capacity of HCT116 cells in vitro and in vivo. Furthermore, endothelial cell tube formation and angiogenesis in chick embryo chorioallantoic membrane (CAM) were accelerated by conditioned medium from ZEB2-overexpressing HCT116 cells. Further, overexpression of ZEB2 accelerated tumor growth and angiogenesis in xenotransplantation models. However, silencing endogenous ZEB2 caused an opposite outcome. Our results provide new evidence that ZEB2 promotes the progression of colon cancer, and thereby might represent a novel therapeutic target for colorectal carcinoma.

Surgical outcomes and prognostic factors of T4 gastric cancer patients without distant metastasis.

OBJECTIVE: To evaluate surgical outcomes and prognostic factors for T4 gastric cancer treated with curative resection. METHODS: Between January 1994 and December 2008, 94 patients diagnosed with histological T4 gastric carcinoma and treated with curative resection were recruited. Patient characteristics, surgical complications, survival, and prognostic factors were analyzed. RESULTS: Postoperative morbidity and mortality were 18.1% and 2.1%, respectively. Multivariate analysis indicated lymph node metastasis (hazard ratio, 2.496; 95% confidence interval, 1.218-5.115; p = 0.012) was independent prognostic factor. CONCLUSIONS: For patients with T4 gastric cancer, lymph node metastasis was associated with poorer survival. Neoadjuvant chemotherapy or aggressive adjuvant chemotherapy after radical resection was strongly recommended for these patients.

[Prognostic value of metastatic lymph node ratio in gastric cancer patients undergoing radical gastrectomy].

OBJECTIVE: To assess the prognostic value of metastatic lymph node ratio in gastric cancer patients undergoing radical gastrectomy (D2). METHODS: Prognostic analysis of 1042 gastric cancer patients undergoing radical gastrectomy (D2) was performed based on metastatic lymph node ratio (MLR), the N staging in the 6th and 7th edition of UICC staging system respectively. Homogeneity, discriminatory ability, and gradient monotonicity of these three staging methods were compared using linear trend χ(2), likelihood ratio χ(2) statistics and Akaike information criterion (AIC) calculations, respectively. The area under the ROC curve (AUC) was calculated to compare the prognostic value of these three staging methods. RESULTS: The 5-year survival rate of 1042 patients was 47.5%. The metastatic lymph node ratio (P<0.01) and N staging of the 7th edition UICC (P<0.05) were independent prognostic factors according to univariate and multivariate analyses. The AUC was 0.754 in MLR staging group, higher than that in N staging of the 6th (0.692) and 7th (0.705) edition of UICC group. Compared to the 6th and 7th edition of UICC N staging group, homogeneity and linear curve were better and AIC value was lower in MLR staging group (7240.017 vs. 7364.073 and 7325.731). CONCLUSION: Prognostic value of MLR staging is better than that of UICC N staging for patients undergoing radical gastric cancer resection. The MLR staging can be a new method of lymph node staging for gastric cancer patients.

Laparoscopic versus open adhesiolysis in patients with adhesive small bowel obstruction: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to evaluate whether surgical outcomes differ between laparoscopy versus the open approach for adhesive small bowel obstruction. METHODS: PubMed, MEDLINE, Embase, and the Cochrane Library databases were electronically searched from 1985 to 2010. The study pooled the effects of outcomes of a total of 334 patients enrolled into 4 retrospective comparative studies using meta-analytic methods. RESULTS: Laparoscopic adhesiolysis was associated with a reduced overall complication rate (odds ratio = .42, .25-.70, P < .01), prolonged ileus rate (odds ratio = .28, .10-.73, P = .01) and pulmonary complication rate (odds ratio = .20, .04-.94, P = .04) compared with the open approach. No significant differences were noted for intraoperative injury to bowel rates (odds ratio = 1.93, .76-4.89, P = .17), wound infection rates (odds ratio = .44, .17-1.12, P = .08), and mortality (odds ratio = .81, .12-5.49, P = .83). CONCLUSIONS: Laparoscopic adhesiolysis is advantageous in most of the analyzed outcomes. Laparoscopic treatment of small bowel obstruction is recommended by experienced laparoscopic surgeons in selected patients.

Combined APACH II score and arterial blood lactate clearance rate to predict the prognosis of ARDS patients.

OBJECTIVE: To explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome (ARDS). METHODS: Blood and biochemical tests and blood-gas analyses were performed upon entry into the ICUs, 12 h, 24 h, 48 h and 72 h after that in 72 ARDS patients (who were admitted to the ICUs of our hospital from January 2000 to December 2009). Then APACHE II scores were achieved by combining relevant physiological parameters and laboratory results. RESULTS: There was a statistical difference between the death group and survival group at different time points upon entering the ICUs in terms of APACHE II score, alveolar-arterial oxygen difference and arterial blood lactate clearance rate. PaO(2)/FiO(2) values were recorded to be statistically different between the death group and survival group 24 h, 48 h and 72 h, respectively after entry into the ICUs. In addition, registered linear regression existed between APACHE II score, alveolar-arterial oxygen difference or PaO(2)/FiO(2) value and time. APACHE II score 24 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) standing respectively at 0.919 and 0.955. Arterial blood lactate clearance rate 12 h, 24 h, 48 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) at 0.918, 0.918, 0.909 and 0.991, respectively. CONCLUSIONS: APACHE II score applied in combination with arterial blood lactate clearance rate is of clinical significance in assessing the prognosis of ARDS patients.

Meta-analysis of laparoscopic versus open colorectal surgery within fast-track perioperative care.

BACKGROUND: Both laparoscopic surgery and fast-track perioperative care have demonstrated advantages in patients undergoing elective colorectal resections. It is unclear whether there is an additive effect by combining these 2 procedures. OBJECTIVE: The study aimed to conduct a meta-analysis of the randomized evidence to compare laparoscopic with open colorectal surgery within fast-track perioperative care. DATA SOURCES: PubMed, MEDLINE, Embase, and the Cochrane library databases were electronically searched (January 1985 to August 2011). STUDY SELECTION: Randomized clinical trials compared laparoscopic with open colorectal resections within fast-track programs. INTERVENTION: Investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria. MAIN OUTCOME MEASURES: The main outcomes measured were postoperative hospital stay, overall hospital stay, readmission rate, morbidity, and mortality. RESULTS: Three trials were considered suitable for meta-analysis. A total of 171 patients underwent laparoscopic surgery, and 142 had open surgery. Meta-analysis showed that laparoscopic colorectal surgery had shorter postoperative hospital stays (weighted mean difference -1.06; 95% CI, -2.06 to -0.06, z = 2.08, p = 0.04) and shorter overall hospital stays (weighted mean difference -2.04; 95% CI, -3.50 to -0.58, z = 2.74, p < 0.01). No significant differences were noted for readmission rate (OR 0.54; 95% CI, 0.26-1.12, z = 1.65, p = 0.10), morbidity (OR 0.68; 95% CI, 0.42-1.10, z =1.58, p = 0.11), and mortality (OR 0.33; 95% CI, 0.09-1.18, z =1.70, p = 0.09). No publication bias and no significant heterogeneity were noted. LIMITATIONS: This study was limited because of its small sample size. CONCLUSIONS: Laparoscopic colorectal surgery has shorter postoperative hospital stays and overall hospital stays than open surgery within fast-track perioperative care. There is no significant difference with respect to readmission rate, morbidity, and mortality. Because the number of patients included in the present trials was small, further studies should be undertaken to confirm these findings.

Superiority of metastatic lymph node ratio to the 7th edition UICC N staging in gastric cancer.

AIM: To compare and evaluate the appropriate prognostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection. METHODS: A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer (UICC) N staging methods and the metastatic lymph node ratio (MLNR) staging. Homogeneity, discriminatory ability, and gradient monotonicity of the various staging methods were compared using linear trend χ(2), likelihood ratio χ(2) statistics, and Akaike information criterion (AIC) calculations. The area under the curve (AUC) was calculated to compare the predictive ability of the aforementioned three staging methods. RESULTS: Optimal cut-points of the MLNR were calculated as MLNR0 (0), MLNR1 (0.01-0.30), MLNR2 (0.31-0.50), and MLNR3 (0.51-1.00). In univariate, multivariate, and stratified analyses, MLNR staging was superior to the 6th and 7th edition UICC N staging methods. MLNR staging had a higher AUC, higher linear trend and likelihood ratio χ(2) scores and lower AIC values than the other two staging methods. CONCLUSION: MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edition UICC N classifications and should be considered as an alternative to current pathological N staging.

Combination of stromal-derived factor-1alpha and vascular endothelial growth factor gene-modified endothelial progenitor cells is more effective for ischemic neovascularization.

BACKGROUND: Recruitment and entrapment of bone marrow-derived endothelial progenitor cells (EPCs) is important in vascular endothelial growth factor (VEGF)-induced angiogenesis. EPC mobilization and differentiation are modulated by stromal-derived factor-1alpha (SDF-1alpha/CXCL12), another important chemokine. In this study, we investigated the hypothesis that SDF-1alpha and VEGF might act synergistically on EPC-mediated vasculogenesis. METHODS: EPCs were isolated and cultured from human peripheral blood, then transduced with retroviral vectors pBabe containing human VEGF(165) complimentary DNA (Td/V-EPCs) and pBabe wild-type (Td/p-EPCs). EPC migration activity was investigated with a modified Boyden chamber assay. EPC apoptosis induced by serum starvation was studied by annexin V assays. The combined effect of local administration of SDF-1alpha and Td/V-EPC transplantation on neovascularization was investigated in a murine model of hind limb ischemia. RESULTS: Over-expression of hVEGF(165) increased SDF-1alpha-mediated EPC migration. SDF-1alpha-mediated migration was significantly increased when EPCs were modified with VEGF (Td/V-EPCs) vs when VEGF was not present (Td/p-EPCs) or when VEGF alone was present (Td/V-EPCs; 196.8 +/- 15.2, 81.2 +/- 9.8, and 67.4 +/- 7.4/mm(2), respectively P < .001). SDF-1alpha combined with VEGF reduced serum starvation-induced apoptosis of EPCs more than SDF-1alpha or VEGF alone (P < .001). To determine the effect of this combination in vivo, SDF-1alpha was locally injected alone into the ischemic hind limb muscle of nude mice or combined with systemically injected Td/V-EPCs. The SDF-1alpha plus VEGF group showed significantly increased local accumulation of EPCs, blood-flow recovery, and capillary density compared with the other groups. The ratio of ischemic/normal blood flow in Td/V-EPCs plus SDF-1alpha group was significantly higher (P < .01), as was capillary density (capillaries/mm(2)), an index of neovascularization (Td/V-EPCs plus SDF-1alpha group, 863 +/- 31; no treatment, 395 +/-13; SDF-1alpha, 520 +/- 29; Td/p-EPCs, 448 +/- 28; Td/p-EPCs plus SDF-1alpha, 620 +/- 29; Td/V-EPCs, 570 +/- 30; P < .01). To investigate a possible mechanistic basis, we showed that VEGF up-regulated the receptor for SDF-1alpha, CXCR4, on EPCs in vitro. CONCLUSION: The combination of SDF-1alpha and VEGF greatly increases EPC-mediated angiogenesis. The use VEGF and SDF-1alpha together, rather than alone, will be a novel and efficient angiogenesis strategy to provide therapeutic neovascularization.

[Laparoscopic versus open appendectomy in patients with chronic appendicitis].

OBJECTIVE: To compare the advantages and disadvantages of laparoscopic versus open appendectomy in patients with chronic appendicitis. METHODS: Two hundred twenty- four patients were divided into laparoscopic group (n=98) and open appendectomy group (n=126) according to individual willing. Prospective non- randomized study was performed to compare the operative time, operative bleeding, hospitalization time, the discovery and management concerned in operation. Abdominal pain in these chronic appendicitis cases was followed up. RESULTS: The operative time was (54.8+/-21.8) min in open group and (51.8+/-18.0) min in laparoscopic group (t=0.80,P > 0.05). The operative bleeding was (18.6+/-23.3) ml in open group and (9.8+/-4.7) ml in laparoscopic group (t=3.13, P < 0.05). The hospitalization time was (8.9+/-5.3) d in open group and (6.8+/-3.0) d in laparoscopic group (t=2.66,P < 0.05). Twenty- five cases had abdominal adhesion in laparoscopic group, including 9 cases of adhesion around appendix, 6 cases of adhesion between ileocecum and anterior or lateral abdominal wall, 4 cases of adhesion between epiploon and abdominal wall or intestines, 6 cases of adhesion around colon and others. All adhesion had been dissected. Fourteen cases adhesion around appendix had been discovered in 126 cases of open group and dissected (chi(2) =7.95,P < 0.05). In follow- up research, 24 cases still had chronic abdominal pain in 98 case of open group, and 9 cases had chronic abdominal pain in 87 of laparoscopic group, the difference was significant (chi(2)=6.29,P < 0.05). CONCLUSION: The laparoscopic appendectomy possesses more advantages in treating chronic appendicitis and can decrease the incidence of chronic abdominal pain after operation.