Foxp3 expression in CD4CD25Foxp3regulatory T cells promotes development of colorectal cancer by inhibiting tumor immunity / 华中科技大学学报（医学）（英德文版）

The mechanism underlying CD4CD25Foxp3regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4CD25Foxp3Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0.01). Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at mRNA level (r=0.526, P=0.036), and was positively correlated with IL-10 at protein level (r=0.314, P=0.030). The Foxp3 expressed in CD4CD25Foxp3Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC (P<0.05 for all). The IL-10 expression was correlated with the histological grade and TNM stage (both P<0.05). The Stat3 expression was correlated with the lymph node metastasis and TNM stage (both P<0.05). It was concluded that CD4CD25Foxp3Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4CD25Foxp3Tregs correlates with CRC progression.

Efficacy and safety of sunitinib on patients with imatinib-resistant gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.</p><p><b>METHODS</b>Clinical data of 48 patients with imatinib-resistant GIST received sunitinib therapy from May 2008 to April 2012 in the Union Hospital of Fujian Medical University were analyzed retrospectively. Eighteen patients received 50 mg/d of sunitinib in a protocol of 4/2 (4 weeks on and 2 weeks off) [50 mg/d (4/2)], and 30 patients received a protocol of 37.5 mg of sunitinib continuous daily dose (37.5 mg/d CDD).</p><p><b>RESULTS</b>The median duration of sunitinib administration of all the 48 patients was 56 weeks, and the short-term efficacy was evaluated at 24 weeks after the initial treatment according to the Choi criteria. The response rate was 27.1% (13/48), including 1 case with complete response (CR), 12 cases with partial response (PR), and 21 cases with stationary disease (SD). The disease control rate was 70.8% (34/48). The mean follow-up time of 48 patients was 89 weeks. The median progression-free survival (PFS) and overall survival (OS) were 48 weeks and 92 weeks respectively. Stratified analyses indicated that the median PFS of patients previously treated by imatinib 400 mg/d and >400 mg/d were 53 weeks and 35 weeks respectively (P=0.018), and the median OS of these two groups were 157 weeks and 71 weeks respectively (P=0.003). Patients with exon 11 mutations had a significantly shorter OS compared with those with exon 9 mutations (71 weeks vs 157 weeks, P=0.008). Hand-foot syndrome was the most common adverse effect (25/48, 52.1%), followed by nausea (24/48, 50.0%), fatigue (23/48, 47.9%), neutropenia(21/48, 41.7%). The sub-group analysis of two protocols of sunitinib administration showed that the incidence of diarrhea and hand-foot syndrome were higher in 50 mg/d (4/2) group than those in 37.5 mg/d CDD group (P=0.027, P=0.048).</p><p><b>CONCLUSIONS</b>Sunitinib is effective for the patients with imatinib-resistant GIST. After 400 mg/d imatinib treatment failure, sunitinib should be prescribed instead of increased dosage of imatinib. Patients with KIT exon 9 mutations present better prognosis than those with KIT exon 11 mutations. The protocol of sunitinib 37.5 mg/d CDD possesses better safety.</p>

Meta analysis of postoperative complications between laparoscopic resection and traditional open resection of mid-low rectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To conduct a meta-analysis of postoperative complications between laparoscopic resection (Group LR) and traditional open resection (Group OR) of mid-low rectal carcinoma.</p><p><b>METHODS</b>Meta analysis was performed by two reviewers, who independently selected and extracted data retrieved from literatures and papers published in China Knowledge Resource Integrated Database (CNKI), Wangfang Data, Foreign Medical Journal Service (FMJS), PubMed, EMBASE and The Cochrane before August 2012 on comparison between two groups. The statistical analysis for research of complex standard was conducted through Revman 5.0.</p><p><b>RESULTS</b>Thirteen clinical case-control studies with a total of 2733 cases were enrolled for analysis, including 1368 cases in Group LR and 1365 in Group OR. The result showed that, compared with Group OR, Group LR had lower overall rate of postoperative complication (OR=0.76, 95%CI:0.62-0.92, P<0.01), lower rate of postoperative intestinal obstruction (OR=0.53, 95%CI:0.35-0.80, P<0.01), lower rate of incision complications (OR=0.43, 95%CI:0.28-0.67, P<0.01), similar incidence of anastomotic bleeding and fistula, and similar incidence of bleeding in abdominal cavity and pelvic cavity (all P>0.05).</p><p><b>CONCLUSIONS</b>The overall rate of postoperative complications of laparoscopic resection for mid-low rectal carcinoma is obviously lower than that of open resection. Laparoscope can be applied safely in the resection of mid-low rectal carcinoma.</p>

Laparoscopic cylindrical abdominoperineal resection with transabdominal approach for lower rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of laparoscopic cylindrical abdominoperineal resection.</p><p><b>METHODS</b>Six patients with rectal adenocarcinoma within 3 cm above the anal verge underwent laparoscopic cylindrical abdominoperineal resection. Transabdominal levator transaction was performed laparoscopically, with no position change during the perineal operation. Pelvic reconstruction was achieved using human acellular dermal matrix mesh in 3 patients.</p><p><b>RESULTS</b>All the procedures were successfully performed without any intraoperative complications, laparoscopy-associated complications, or conversion to the open approach. The mean operation time was 186.7 minutes and intraoperative blood loss was 101.7 ml. All the specimens had a cylindrical shape with levator muscles attached to the mesorectum and circumferential margins were all negative. No adverse incidence followed the pelvic reconstruction using human acellular dermal matrix mesh.</p><p><b>CONCLUSIONS</b>Laparoscopic transabdominal transection of the levator muscles without position change and pelvic floor reconstruction with human acellular dermal matrix mesh is feasible. This procedure simplifies cylindrical abdominoperineal resection which is aggressively invasive and technically complicated. The oncologic outcomes are acceptable and complications are less.</p>

Interleukin-18 and -12 synergistically enhance cytotoxic functions of tumor-infiltrating lymphocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is not clear and is a challenge for anti-tumor immunotherapy. This study aimed to investigate the effects of interleukin (IL)-18 and -12 on cytotoxic functions of TILs.</p><p><b>METHODS</b>TILs from postoperative gastric cancer patients were costimulated with IL-18 and IL-12. SGC-7901 tumor cells were pre-incubated with TILs and subcutaneously injected into BALB/C SCID mice. The function of TILs was evaluated by measuring tumor sizes in tumor-bearing mice, T helper (Th)1 (tumor necrosis factor (TNF)-α, interferon (IFN)-γ) and Th2 cytokine levels (IL-10 and IL-4) in serum and cytotoxicity of mouse natural killer (NK) and CD8(+) T cells.</p><p><b>RESULTS</b>IL-18 and IL-12 synergistically inhibited the growth of SGC-7901 cells in vivo and significantly extended the survival rate of SGC-7901-bearing mice (66.7% vs. 13.7%, P < 0.01). Moreover, TILs could promote the secretion of TNF-α and IFN-γ ((130.34 ± 7.65) vs. (210.63 ± 12.31) pg/ml, P < 0.01; (14.23 ± 1.97) vs. (30.52 ± 2.12) pg/ml, P < 0.01), and downregulate IL-10 and IL-4 secretion ((103.72 ± 11.21) vs. (61.36 ± 5.41) pg/ml, P = 0.021; (49.36 ± 4.67) vs. (28.48 ± 3.86) pg/ml, P = 0.024).</p><p><b>CONCLUSION</b>IL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human gastric cancer.</p>

Short-term efficacy of laparoscopic-assisted right hemicolectomy with D3 lymph node dissection in colon cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility and short-term efficacy of laparoscopic-assisted D3 lymph node dissection for right colon cancer with a medial-to-lateral approach.</p><p><b>METHODS</b>Clinical data of 61 patients with right colon cancer undergoing D3 lymph node dissection from March 2006 to June 2010 were analyzed retrospectively. Among them,29 underwent laparoscopic-assisted right hemicolectomy (LARH group) and 32 underwent open right hemicolectomy (ORH group). The number of lymph node harvest, operative details, and complication rate were compared between the two groups.</p><p><b>RESULTS</b>The mean number of lymph node harvest did not differ significantly between the two groups (16.9±3.8 vs. 15.4±3.6). As compared to ORH group, although the operative time was significantly longer [(214.4±37.9) min vs. (193.3±28.8) min] in LARH group, the mean blood loss [(83.4±38.0) ml vs. (192.7±43.6) ml], time to first flatus [(44.6±20.8) h vs. (70.4±80.0) h], time to resumption of soft diet[(32.5±10.6) h vs. (59.7±10.4) h], and postoperative hospital stay [(11.2±2.2) d vs. (13.8±2.8) d] were more favorable(all P<0.05). Complication rate was lower in LARH group(10.4% vs. 9.4%), however the difference was not statistically significant.</p><p><b>CONCLUSIONS</b>LARH with D3 lymph node dissection is oncologically comparable with ORH for right colon cancer. It is a safe and feasible procedure associated with rapid postoperative recovery.</p>