BackgroundThe incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing worldwide. We investigated the clinicopathological characteristics of patients with Siewert type II and III AEGs and clarified the optimal intra-abdominal lymph node dissection in these patients.MethodsThis study included 132 patients with AEG who underwent curative resection at Shizuoka Cancer Center from September 2002 to December 2012. We used the index of estimated benefit from lymph node dissection (IEBLD) to assess the efficacy of lymph node dissection of each station. The clinicopathological characteristics and IEBLDs of each station were compared between patients with Siewert type II and III AEGs.ResultsWe analyzed 92 patients with Siewert type II AEG and 40 patients with Siewert type III AEG. The incidence of lymph node metastasis was high in both groups (64.1 % in type II AEG and 75.0 % in type III AEG). The 5-year survival rates were similar for the patients with Siewert type II and III AEGs, at 54.0 and 53.4 %, respectively. The IEBLDs of stations located near the esophagogastric junction were generally high in both groups, while the IEBLDs of lower perigastric lymph nodes were higher in Siewert type III than in Siewert type II AEG cases.ConclusionsThe IEBLDs were similar between Siewert type II and III AEGs at all stations except for lower perigastric lymph nodes. Total gastrectomy should be selected as a standard treatment for Siewert type III AEG, whereas in Siewert type II AEG, preservation of the distal part of the stomach may be an acceptable procedure.
Excessive visceral fat, represented by the VFA, was found to be an independent risk factor for both pancreas-related infection and anastomotic leakage following gastrectomy.
Background The enhanced recovery after surgery (ERAS) protocol integrates a number of perioperative interventions and techniques, aiming at decreasing the morbidity rate and the length of postoperative hospital stay after surgery. Although it has become a standard perioperative management for colorectal surgery, the feasibility of the ERAS protocol for gastric surgery remains unclear. Methods This single-center, prospective phase II study included patients with gastric cancer undergoing curative gastrectomy. The primary end point was the incidence of Clavien-Dindo grade II or higher postoperative complications. The secondary end points were the incidence of anastomotic leakage, the incidence of pneumonia, the proportion of patients starting oral feeding at postoperative day 2, the completion rate of the ERAS protocol, the length of postoperative hospital stay, the readmission rate within 30 days after discharge, and the mortality rate. Results From September 2013 to September 2014, 121 eligible patients were enrolled in this study. The incidence of postoperative complications was 10.7 % (90 % confidence interval, 6.47-16.54 %). Anastomotic leakage and pneumonia was observed in one and zero patients, respectively. The median length of postoperative hospital stay was 8 days, and the completion rate of the ERAS protocol was 85.1 %. The readmission rate and the mortality rate were 0 %. Conclusions The ERAS protocol can be safely used in patients undergoing gastric cancer surgery. The superiority of the ERAS protocol over non-ERAS perioperative management should be clarified.
Multidrug resistance (MDR) caused by the overexpression of ATPbinding cassette (ABC) transporters in cancer cells is a major obstacle in cancer chemotherapy. Previous studies have shown that curcumin, a natural product and a dietary constituent of turmeric, inhibits the function of MDR-related ABC transporters, including ABCB1, ABCC1, and especially ABCG2. However, the limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinical setting. In this study, we investigated the effects of 24 synthetic curcumin analogs with increased bioavailability on the transport function of ABCG2. The screening of the 24 synthetic analogs by means of flow cytometry revealed that four of the curcumin analogs (GO-Y030, GO-Y078, GO-Y168, and GO-Y172) significantly inhibited the efflux of the ABCG2 substrates, mitoxantrone and pheophorbide A, from ABCG2-overexpressing K562/breast cancer resistance protein (BCRP) cells. Biochemical analyses showed that GO-Y030, GO-Y078, and GO-Y172 stimulated the ATPase activity of ABCG2 at nanomolar concentrations and inhibited the photolabeling of ABCG2 with iodoarylazidoprazosin, suggesting that these analogs interact with the substrate-binding sites of ABCG2. In addition, when used in cytotoxicity assays, GO-Y030 and GO-Y078 were found to improve the sensitivity of the anticancer drug, SN-38, in K562/BCRP cells. Taken together, these results suggest that nontoxic synthetic curcumin analogs with increased bioavailability, especially GO-Y030 and GO-Y078, inhibit the function of ABCG2 by directly interacting at the substrate-binding site. These synthetic curcumin analogs could therefore be developed as potent modulators to overcome ABCG2-mediated MDR in cancer cells.
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