Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRAAA and GRp) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRa and GRp in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n - 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRa and GRp expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRa and GRp expression. Both positive association between GRa expression and the response of UC to GC and strong negative association between GRp expression and the response of UC to GC were identified. There was no significant association between GRa/GRp expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRa and GRp may play an important role in the action of GC, and that GRp functions as a dominant negative inhibitor of GRa. Expression of GRa and GRp in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients:a multicenter randomized-controlled trial

Background:Data from single-center experience or small sample-sized studies have shown that chromoendoscopy(CE)might be superior to white-light endoscopy(WLE)for dysplasia surveillance in ulcerative colitis(UC)patients.We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies(WLT),WLE with random biopsies(WLR),and dye-based CE with targeted biopsies(CET)in UC patients.Methods:Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms(WLT,WLR,and CET).Only high-definition endoscopy was used in all three groups.The patients were followed up by annual endoscopy with biopsies through December 2017.Results:With a median follow-up time of 55 months,a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set:WLT(n=43),WLR(n=40),and CET(n=39).A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients.WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT(8.1%and 9.7%vs 1.9%;P=0.014 and 0.004,respectively).WLR obtained more biopsied samples than WLT and CET(16.465.1 vs 4.361.4 and 4.361.4;both P<0.001).During the second half of the follow-up(37-69 months),CET could identify more colonoscopies that diagnosed dysplasia than WLT(13.3%vs 1.6%,P=0.015)and showed a trend for increasing the detection rate compared with WLR(13.3%vs 4.9%,P=0.107).Conclusions:For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC,CET appeared to be more effective thanWLT and less tedious than WLR.CET was found to be particularly useful when a long-term(>3 years)follow-up was conducted for dysplasia surveillance.The trial was registered on www.chictr.org.cn(ChiCTR1900023689).