Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality. Although advances have been made in understanding the pathogenesis of PDAC, the outcome still remains poor. The aim of this study is to conduct a meta-analysis to evaluate the precise association between SMAD4 loss and clinicopathological significance in PDAC. A literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, Odds Ratio or Hazard Ratio with corresponding confidence intervals was calculated and summarized. 12 relevant articles were included for full review in detail and meta-analysis. The frequency of SMAD4 protein loss was significantly increased in PDAC than in nonmalignant pancreatic tissue, Odd Ratio was 0.05 with 95% confidence interval 0.01-0.23, p<0.0001. SMAD4 loss was significantly associated with poor overall survival in patients with PDAC, Hazard Ratio was 0.61 with 95% confidence interval 0.38-0.99, p=0.05. SMAD4 loss was not correlated with the size, grades, and lymph node metastasis of PDAC. In conclusion, SMAD4 is a biomarker for the diagnosis of PDAC. SMAD4 loss is significantly related to poor prognosis in patients with PDAC.

Comparison of Delta-Shape Anastomosis and Extracorporeal Billroth I Anastomosis after Laparoscopic Distal Gastrectomy for Gastric Cancer: A Systematic Review with Meta-Analysis of Short-Term Outcomes.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate the safety and relative benefits of delta-shape anastomosis (DA) by comparing to conventional laparoscopy-assisted distal gastrectomy with Billroth I gastroduodenostomy (LADG BI). METHODS: Studies and relevant literature regarding DA versus LADG BI were searched in the electronic databases. Operation time, postoperative complications, estimated blood loss, number of retrieved lymph nodes, time to first flatus, time to oral intake, length of postoperative hospitalization in DA and LADG BI were pooled and compared using meta-analysis. Weighted mean differences (WMDs) and odds ratios (ORs) were calculated with 95% confidence intervals (CIs) to evaluate the effect of DA. RESULTS: Eight studies of 1739 patients were included in the meta-analysis. Compared with LADG BI, DA had shorter postoperative hospitalization (WMD = -0.47, 95%CI: -0.69 to -0.25, P<0.01), less blood loss (WMD = - 25.90, 95%CI: -43.11 to -8.70, P<0.01), shorter time to oral intake (WMD = -0.25, 95%CI: -0.49 to -0.01, P = 0.04), and more retrieved lymph nodes (WMD = 1.36, 95%CI: 0.30 to 2.43, P = 0.01). Operation time (WMD = -0.07, 95%CI -15.58 to 15.43, P = 0.99), overall postoperative complication rate (OR = 1.05, 95%CI: 0.74 to 1.49, P = 0.63), surgical complication rate (OR = 1.02, 95%CI: 0.70 to 1.49, P = 0.90), nonsurgical complication rate (OR = 1.21, 95%CI: 0.54 to 2.72, P = 0.64), leakage rate (OR = 2.54, 95%CI: 0.92 to 7.01, P = 0.07), stricture rate (OR = 0.36, 95%CI: 0.09 to 1.44, P = 0.15), wound complication rate (OR = 0.71, 95%CI: 0.33 to 1.55, P = 0.39), time to first flatus (WMD = -0.10, 95%CI: -0.27 to 0.07, P = 0.26), and proximal surgical margin (WMD = -0.25, 95%CI: -1.14 to 0.65, P = 0.59) was not statistically different. CONCLUSION: Compared with LADG BI, DA is a safe and feasible procedure, with significantly reduced blood loss, time to oral intake, and postoperative hospitalization.

Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.

Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer.

Prognostic value of microRNA-21 in pancreatic ductal adenocarcinoma: a meta-analysis.

BACKGROUND: Recently, microRNA-21 (miR-21) has been reported to be associated with prognosis of pancreatic ductal adenocarcinoma (PDAC). The present studies aimed to evaluate the prognostic value of miR-21 for PDAC with meta-analysis. METHODS: A systematic search in the PubMed and other databases was conducted to identify eligible studies. The pooled hazard ratios (HRs) with 95% confidence interval (CI) were calculated. The meta-analysis was conducted using the STATA 12.0 software. RESULTS: A total of 12 articles (13 studies) which included 963 cases were selected for the meta-analysis. Elevated miR-21 expression was significantly predictive of poor overall survival (HR = 2.05, 95% CI 1.71-2.46, P < 0.001). In the subgroup analyses, similar results were observed in Asian (HR = 2.09, 95% CI 1.62-2.71, P < 0.001) and Caucasian (HR = 2.36, 95% CI 1.53-3.65, P < 0.001); in tissue sample (HR = 2.14, 95% CI 1.73-2.65, P < 0.001) and serum sample (HR = 1.84, 95% CI 1.30-2.60, P = 0.001); with quantitative real-time polymerase chain reaction assay method (HR = 2.31, 95% CI 1.86-2.86, P < 0.001); and in patients receiving adjuvant chemotherapy (HR = 2.37, 95% CI 1.88-3.00, P < 0.001). The association between miR-21 expression level and lymph node metastasis was statistically significant (OR = 1.45, 95% CI 1.02-2.06, P = 0.038). However, no significant relationship between miR-21 expression level and sex or vascular invasion or neural infiltration was observed (P > 0.05). CONCLUSIONS: Our meta-analysis indicated that elevated miR-21 expression level can predict poor prognosis in patients with PDAC.

[Laparoscopic-assisted radical distal gastrectomy in treatment of invasive gastric cancer: analysis of 47 cases].

OBJECTIVE: To investigate the clinical effect of laparoscopic-assisted radical distal resection of invasive gastric cancer. METHODS: Forty-seven patients with advanced gastric cancer, 33 males and 14 females, aged 58.2 (36 - 77), underwent laparoscopic-assisted radical resection and then were followed up for 17 months (2 - 33 months). RESULTS: All the 47 patients survived. The operation time was (294 +/- 75) min (200 - 420 min). The blood loss was (150 +/- 65) ml (50 - 500 ml). The number of dissected lymph nodes was (32.4 +/- 22.3) (15 - 48). The gastrointestinal peristalsis recovery time after operation was (2.7 +/- 1.2) d (2 - 6 d). The hospital stay time was (9.0 +/- 3.5) d (5 - 19 d). Post-operational complications were seen in 3 cases: pulmonary infection in 2 cases and incision infection in 1 case, and all the 3 patients recovered well after proper treatment. CONCLUSION: Laparoscopic-assisted radical resection of invasive gastric cancer is safe and feasible, with the advantages as minimal invasion, less pain, shorter hospital stay, faster bowel function recovery.