Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer.

The present study evaluated the efficacy of Roux-en-Y (R-Y) reconstruction and Billroth-I (B-I) reconstruction after laparoscopy-assisted distal gastrectomy (LADG). Between October 2000 and February 2006, a total of 133 consecutive patients who underwent LADG for gastric carcinoma were classified into 2 groups according to reconstruction (B-I, n = 65; R-Y, n = 68). Parameters analyzed included patients and tumor characteristics, operative details, postoperative outcomes, and nourishment state. Endoscopic findings of the gastric remnant and lower esophagus were evaluated at 12 months postoperatively. Regarding postoperative complications, no significant differences were found between groups. In the B-I group, 3 patients developed anastomotic leakage and 4 patients suffered anastomotic stricture requiring endoscopic balloon dilation. So-called functional stasis after R-Y reconstruction was not found in this study. Incidence of heartburn at 12 months postoperatively was 37% in the B-I group and 8% in the R-Y group (P = 0.0002). Amount of meal consumed compared with preoperative value at 12 months postoperatively was significantly higher for the R-Y group than for the B-I group (83.6% ± 15.3% vs. 77.8% ± 16.0%; P = 0.047). Endoscopic findings showed that incidence of remnant gastritis was significantly lower in the R-Y group than in the B-I group (12% vs. 34%; P = 0.002). Bile reflux into the remnant stomach was not observed in the R-Y group. R-Y reconstruction seems superior to B-I reconstruction for preventing both bile reflux into the gastric remnant and postoperative complications. We consider R-Y reconstruction as a feasible and safe method for LADG.

Background: The role of human epidermal growth factor receptor (HER) 3 and HER4 has been elucidated in gastric cancer. HER1 and HER2 overexpression are regarded as prognostic factors and targets of treatment. The dimerization of the HER family receptors activates downstream signal pathways and promotes tumor progression. This study investigated the positive correlation between HER1 and HER4 expression and the prognosis of patients with gastric cancers. Experimental Design: Tumor samples were obtained from gastric adenocarcinomas of 134 patients who underwent a gastrectomy from 1999 to 2002. The expression of each HER was analyzed in the tumor by immunohistochemical staining. Parametric correlations were done between HER expression and the clinicopathologic findings. A multivariate analysis was done with the overall survival. Results: HER3 expression was significantly associated with parameters involved with tumor progression, including the depth of tumor invasion (T₁ versus T₂-T₄; P = 0.000), involved lymph nodes (P = 0.000), distant metastasis (P = 0.008), tumor stage (P = 0.000), and recurrent disease (P = 0.000). HER1 was also significantly associated with those factors excluding distant metastasis. A significant relationship was observed between the expression of HER1 and HER3 (P = 0.000). HER3 overexpression was associated with a significantly worse survival (P = 0.0000) and was an independent prognostic factor in the multivariate analysis (hazard ratio, 2.382; 95% confidence interval, 1.009-5.625; P = 0.048). Conclusions: HER3 overexpression is strongly associated with tumor progression and poor prognosis of patients with gastric cancer. It may become a new prognostic factor and a target of treatment.

AIM: To investigate the anastomotic complications of esophagojejunostomy (EJS) after laparoscopic total gastrectomy (LTG), we reviewed retrospective studies. METHODS: A literature search was conducted in PubMed for studies published from January 1, 1994 through January 31, 2015. The search terms included “laparoscopic,”“total gastrectomy,” and “gastric cancer.” First, we selected 16 non-randomized controlled trials (RCTs) comparing LTG with open total gastrectomy (OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system (NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0% (30 of 984 patients) among LTG procedures and 2.1% (31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG (odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I² = 0%). Anastomotic stenosis related to EJS was reported in 72 (2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG (OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I² = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar (1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the OrVil^TM device was used (8.8%) compared with other procedures (1.0% to 3.6%). CONCLUSION: The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the OrVil^TM device was used.

The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2–4, P=0.003), involved lymph nodes (P=0.010), and tumour stage (I vs II–IV, P=0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (P<0.001,=0.035, and <0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P=0.037) and overall survival (OS, P=0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P=0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.