Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT.

Membrane type 1-matrix metalloproteinase (MT1-MMP) has been identified to play a significant role in several types of cancers, but little is known about the significance of MT1-MMP in gastric cancer patients. The purpose of this study is to investigate the involvement of MT1-MMP in tumor progression of gastric cancer. MT1-MMP expression levels were examined in gastric cancer tissues and cells, and normal gastric tissues and cells. The effects and molecular mechanisms of MT1-MMP expression on cell proliferation, migration, and invasion were also explored. In our results, MT1-MMP messenger RNA (mRNA) and protein expression levels were significantly increased in gastric cancer tissue. Moreover, the overexpression of MT1-MMP was positively associated with the status of clinical stage and lymph node metastasis through real-time PCR. Furthermore, knocking down MT1-MMP expression significantly suppressed the cell migration and invasion in vitro and regulated the expression of MMPs and epithelial-mesenchymal transition (EMT)-associated genes. In conclusions, our study demonstrates that MT1-MMP was overexpressed in gastric cancer tissue, and reduced expression of MT1-MMP suppressed cell migration, invasion, and through regulating the expression of MMPs and the process of EMT in gastric cancer.

Extended multi-organ resection for cT4 gastric carcinoma: A retrospective analysis.

OBJECTIVE: Combined resection for locally advanced (T4) gastric cancer may result in high morbidity and mortality. The aim of this study was to evaluate the clinicopathologic characteristics to determine the prognostic factors for T4 gastric cancers. METHODOLOGY: A total of 463 consecutive patients with gastric cancers were enrolled in this study. Among them, 63 patients received combined resections. Various clinicopathologic factors influencing survival rates were evaluated. Survival rates were calculated according to the Kaplan-Meier method. Prognostic factors were evaluated by the univariate and multivariate analysis. RESULTS: Thirty-one patients (49.2%) received one additional organ resection and 32 patients (50.8%) received two or more additional organ resections. Curative resection was performed in 49 patients (77.8%). Multivariate analysis identified curative resection (hazard ratio 0.330; 95 percent confidence interval, 0.139-0.784; P = 0.012) and tumor diameter (> 7 cm) (hazard ratio, 3.589; the 95 percent confidence interval, 1.425-9.037; P = 0.007) as independent prognostic factor for patients with T4 gastric cancer undergoing combined resection. CONCLUSIONS: The use of aggressive multi-organ resection was recommended for patients with T4 gastric carcinoma, with tumor diameter as a useful indicator. Patients with relatively small tumor diameter (≤ 7cm) could benefit from multi-organ resections.

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.

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.

Transanal versus transabdominal specimen extraction in laparoscopic rectal cancer surgery: a retrospective analysis from China.

INTRODUCTION: Comparison of transanal specimen extraction (TSE) and transabdominal specimen extraction (TASE) in laparoscopic rectal surgery is still sparsely reported. Trauma, pain, scarring, and bad psychological suggestion have long been considered an inevitable outcome of surgery. For laparoscopic rectal cancer surgery, whether TSE or TASE is beneficial in terms of technical platforms, indications, contraindications, technical requirements for aseptic operation, tumor-free operation, prevention and treatment of complications still has not reached a unified consensus and standards. Recently, comparison of TSE and TASE in laparoscopic rectal surgery has still been sparsely reported. AIM: In this study, we retrospectively analyzed the short-term outcomes of TSE and TASE in laparoscopic rectal surgery in a single institution in southern China. MATERIAL AND METHODS: Patients who underwent laparoscopic radical rectal cancer surgery using either TSE or TASE were recruited. Data, including patient demographics, perioperative and postoperative variables, were analyzed retrospectively. RESULTS: Sixty-seven patients were included in this study. Thirty patients underwent TSE and 37 patients underwent TASE. The two groups were similar in demographics and tumor characteristics. Postoperative complications were similar in both groups, except that wound infection was lower for the TSE group (p = 0.122). The TSE group had a better cosmetic result with no abdominal incision and no differences in circumferential margins, distal resection margins or completeness of total mesorectal excision. CONCLUSIONS: Laparoscopic TSE is recommended in the treatment of rectal cancer with similar oncologic outcomes compared with conventional TASE. It is mini-invasive surgery and has the advantage of better cosmetic results. There is a need for further randomized studies to refine the applicability of laparoscopic TSE in rectal cancer.

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.

Susceptibility and REF1 gene polymorphism towards colorectal cancer.

Published data on the relation between REF1 polymorphism and colorectal cancer risk showed inconclusive results. The aim of this study was to derive a comprehensive estimation of the association. Data on association between REF1 polymorphism and colorectal cancer risk were summarized. The association was estimated by calculating an odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) with the fixed effects model when P > 0.1 (from heterogeneity test) or with the random effects model when P < 0.1. No significant association was revealed in any genetic model assumed for the overall analysis (OR = 1.03, 95 % CI = 0.81-1.32 for Glu/Glu vs. Asp/Asp; OR = 1.05, 95 % CI = 0.96-1.15 for Glu/Glu + Asp/Glu vs. Asp/Asp; OR = 0.97, 95 % CI = 0.76-1.23 for Glu/Glu vs. Asp/Glu + Asp/Asp; OR = 1.03, 95 % CI = 0.92-1.16 for Glu vs. Asp; OR = 1.09, 95 % CI = 0.93-1.27 for Asp/Glu vs. Asp/Asp). In Caucasian population, nor did we find a significant association. This research indicates that REF1 polymorphism is unlikely to be associated with colorectal cancer risk.

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.

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.

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.

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.

[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.