Regulatory T Cells Promote Overexpression of Lgr5 on Gastric Cancer Cells via TGF-beta1 and Confer Poor Prognosis in Gastric Cancer.

Background: The leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is considered a cancer stem cell marker, and is often overexpressed in tumors. The interaction between Lgr5 and the immune-related tumor microenvironment is not completely understood. The aim of this study was to examine the role of Lgr5 in the microenvironment of gastric cancer (GC), and to explore possible immunological mechanisms influencing Lgr5 expression that are governed by regulatory T cells. Methods: Lgr5 expression was examined in 180 GC tumors by immunohistochemistry, and in 80 pairs of GC tumors for analysis of Th1/Th2 cytokines by ELISA. In addition, SGC7901 cells were co-cultured with patient-derived Tregs, varying concentrations of TGF-ß1, TGF-ß1 neutralizing antibody, or TGF-ß receptor inhibitor SB431542, and Lgr5 and ß-catenin expression were examined by qRT-PCR and western blot. Results: In this study, an immunosuppressive microenvironment was associated with high Lgr5 expression in GC. Furthermore, Lgr5 expression was up-regulated in GC cells co-cultured with Tregs or treated with exogenous TGF-ß1. This up-regulation was partially inhibited by the TGF-ß1 neutralizing antibody, or TGF-ß1 receptor antagonist SB431542. ß-catenin was up-regulated with high Lgr5 expression induced by exogenous TGF-ß1, and this up-regulation was inhibited by SB431542. An increased number of Tregs and high Lgr5 expression in GC tissues were significantly associated with low overall survival. Conclusion: Tregs promoted increased Lgr5 expression in GC cells via TGF-ß1 and TGF-ß1 signaling pathway, which may involve activation of the Wnt signaling pathway. High Lgr5 expression via TGF-ß confer poor prognosis in gastric cancer.

Comparison of hand-assisted laparoscopy with open total colectomy for slow transit constipation: a retrospective study.

OBJECTIVE: To compare the efficacy and safety of hand-assisted laparoscopic colectomy (HALC) and open colectomy (OC) for patients with slow transit constipation (STC). METHODS: Data of patients with STC who underwent total colectomy from January 2008 to December 2012 were retrospectively reviewed after clinical evaluation and an exclusion of secondary causes. These patients were further divided into the HALC and OC groups. Patients' outcomes, including intraoperative and postoperative data on their recovery and complications were compared between the two groups. RESULTS: A total of 68 patients with STC were finally enrolled in the study, including 32 in the HALC group and 36 in the OC group. The baseline characteristics did not significantly differ between the two groups. Compared with the OC group, patients in the HALC group had a shorter length of incision, a longer operative time and less blood loss volume. There was no conversion to OC for patients undergoing HALC and no intraoperative complications in both groups. Furthermore, after operation, patients in HALC group experienced less pain (3.4 ± 0.7 vs 4.8 ± 1.0), earlier first passage of flatus (58.3 ± 6.3 h vs 73.4 ± 13.0 h), shorter length of postoperative hospital stay (8.8 ± 1.2 days vs 11.3 ± 1.7 days) but higher medical cost (RMB 33 979 ± 3 135 vs RMB 29 828 ± 3 216). The overall postoperative complications and the satisfaction in defecation were comparable in the two groups. CONCLUSION: HALC is a safe, minimally invasive and effective surgical alternative for treating STC, which is comparable to OC.

Hand-assisted laparoscopic versus open right hemicolectomy: short-term outcomes in a single institution from China.

AIM: To compare the perioperative parameters and short-term outcomes of hand-assisted laparoscopic colectomy (HALC) and open colectomy (OC) for the treatment of patients with cancer of the right hemicolon. METHODS: Patients who were scheduled to perform right hemicolectomy between August 2009 and December 2010 were randomized into either HALC or OC group. Patients were excluded if they had synchronous cancers, hepatic metastases, acute intestinal obstruction, or intestinal perforations. All the operations in the 2 groups were performed by a single surgical team. Measured outcomes included the demographic variables and perioperative parameters. The former included age, sex, body mass index, American Society of Anesthesiologists class, prior abdominal surgery, distribution of tumors, and histopathologic stage; whereas the latter included length of incision, operative time, estimated blood loss, conversion rate, number of lymph nodes retrieved, postoperative pain score, time to return of bowel function, postoperative complications, duration of hospital stay, and total cost. RESULTS: One hundred sixteen patients with cancer of the right hemicolon (HALC=59, OC=57) were recruited. The 2 groups of patients were similar in age, sex distribution, body mass index, American Society of Anesthesiologists class, and previous abdominal surgery. No significant difference was observed between the 2 groups in terms of distribution of tumors and the final histopathologic staging. HALC had a significantly shorter incision length and longer operative time than OC. Patients in the HALC group had significantly less operative blood loss, less pain and earlier passage of flatus after operation than those in the OC group. The number of lymph nodes recovered in the specimen and the overall postoperative complications was comparable in the 2 groups. The postoperative duration of hospital stay was significantly shorter in the HALC group, whereas the median overall costs in the HALC group were significantly higher than that in the OC group. CONCLUSIONS: The results from the present study demonstrate that the HALC is a valid surgical approach for cancer of the right hemicolon that retains the benefits of minimally invasive surgery. We believe that this technique is a safe, useful, and feasible method for patients with right-sided colonic cancer. If practiced more, it might be advocated as a "bridge" between traditional laparoscopic surgery and conventional open procedures.