Laparoscopic resection is better than endoscopic dissection for gastric gastrointestinal stromal tumor between 2 and 5 cm in size: a case-matched study in a gastrointestinal center.

BACKGROUND: The feasibility of endoscopic dissection for gastric gastrointestinal stromal tumor (gGIST) between 2 and 5 cm in size has been demonstrated. However, its impact on short-term and long-term outcomes, compared with laparoscopic resection, is unknown. The purpose of this study was to compare short-term and long-term outcomes between laparoscopic resection and endoscopic dissection for 2-5-cm gGIST. METHODS: A case-matched study was performed using the propensity score. To overcome selection bias, we performed a 1:1 match using six covariates, including age, sex, BMI, ASA score, tumor size, and tumor location. Short-term and long-term outcomes between laparoscopic resection and endoscopic dissection were compared. RESULTS: A total of 210 patients with 2-5-cm gGIST were enrolled between 2006 and 2017 in our gastrointestinal center. According to the intention-to-treat approach, 165 patients underwent laparoscopic resection, and 45 patients underwent endoscopic dissection. After the propensity score, 45 pairs were balanced and analyzed. There was no significant difference in the baseline characteristics between the laparoscopic and endoscopic groups after matching. The rate of complications was significantly higher in the endoscopic group compared with the laparoscopic group (P < 0.001). Perforations occurred in 16 patients in the endoscopic group (16/45, 35.6%). The postoperative hospital stay was significantly longer in the endoscopic group compared with the laparoscopic group (P < 0.001). There was no significant difference between the two groups in disease-free survival or overall survival. CONCLUSION: Laparoscopic resection is better than endoscopic dissection for 2-5-cm gGIST because of the lower complication rate and shorter hospital stay.

Git2 deficiency promotes MDSCs recruitment in intestine via NF-κB-CXCL1/CXCL12 pathway and ameliorates necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants and the most common cause of neonatal death, whereas the molecular mechanism of intestinal injury remains unclear accompanied by deficiency of effective therapeutic approaches. GIT2 (G-protein-coupled receptor kinase interacting proteins 2) can affect innate and adaptive immunity and has been involved in multiple inflammatory disorders. In this study, we investigated whether GIT2 participates in the pathogenesis of NEC. Here we found that intestinal Git2 gene expression was significantly increased in NEC patients and NEC mice, which positively correlated with the tissue damage severity, and Git2 deficiency could potently protect against NEC development in mice. Mechanistically, Git2 gene knockout dramatically increased the recruitment of MDSCs in the intestine, and in vivo depletion of MDSCs almost completely abrogated the protective effect of Git2 deficiency on NEC. Moreover, Git2 deficiency induced MDSCs intestinal accumulation mainly relied on CXCL1/CXCL12 signaling, as evidenced by the significant increment of CXCL1 and CXCL12 levels in intestinal epithelium of Git2-/- mice and dramatically decrease of MDSCs accumulation in intestine as well as increase of NEC severity upon treatment of CXCL1/CXCL12 pathway inhibitors. In addition, Git2 deficiency induced up-regulation of CXCL1 and CXCL12 is at least partially mediated through activating NF-κB signaling. Thus, our findings suggest that GIT2 is involved in the pathogenesis of NEC, and targeting GIT2 may be a potential preventive and therapeutic approach for NEC.

Gut microbial metabolite deoxycholic acid facilitates Th17 differentiation through modulating cholesterol biosynthesis and participates in high-fat diet-associated colonic inflammation.

BACKGROUND: High-fat diet (HFD) is closely associated with the increased prevalence of inflammatory bowel disease (IBD). Excessive gut microbial metabolite deoxycholic acid (DCA) caused by HFD plays significant roles in eliciting intestinal inflammation, however, the mechanism underlining the induction of inflammatory response by DCA has not been fully elucidated. The purpose of this study was to investigate the role of DCA in the triggering of inflammation via affecting CD4+ T cell differentiation. RESULTS: Murine CD4+T cells were cultured under Th1, Th2 or Th17-polarizing conditions treated with or without different dosage of DCA, and flowcytometry was conducted to detect the effect of DCA on CD4+ T cell differentiation. Alteration of gene expression in CD4+ T cells upon DCA treatment was determined by RNA-sequencing and qRT-PCR. Bioinformatic analysis, cholesterol metabolic profiling, ChIP assay and immuno-fluorescent staining were further applied to explore the DCA-regulated pathway that involved in CD4+T cell differentiation. The results showed that DCA could dose-dependently promote the differentiation of CD4+ T cell into Th17 linage with pathogenic signature. Mechanistically, DCA stimulated the expression of cholesterol biosynthetic enzymes CYP51 and led to the increased generation of endogenous RORγt agonists, including zymosterol and desmosterol, therefore facilitating Th17 differentiation. Up-regulation of CYP51 by DCA was largely mediated via targeting transcription factor SREBP2 and at least partially through bile acid receptor TGR5. In addition, DCA-supplemented diet significantly increased intestinal Th17 cell infiltration and exacerbated TNBS-induced colitis. Administration of cholestyramine to eliminate fecal bile acid obviously alleviated colonic inflammation accompanied by decreased Th17 cells in HFD-fed mice. CONCLUSIONS: Our data establish a link between DCA-induced cholesterol biosynthesis in immune cells and gut inflammation. Modulation of bile acid level or targeting cholesterol metabolic pathway may be potential therapeutic measurements for HFD-related colitis.