Combined serum albumin, fecal immunochemical test, and leucine-rich alpha-2 glycoprotein levels for predicting prognosis in remitting patients with ulcerative colitis.

This study investigated the usefulness of serum leucine-rich alpha-2 glycoprotein (LRG) and fecal immunochemical tests (FIT) for predicting relapse in patients with ulcerative colitis (UC). Data of 194 patients tested for LRG between January 2020 and June 2022 were retrospectively collected and clinical characteristics were recorded. LRG was strongly correlated with CRP levels and it had a moderately negative correlation with albumin levels, whereas FIT was not significantly correlated with either CRP or albumin levels. Furthermore, the median serum albumin and FIT were significantly different between patients with or without clinical relapse; while the LRG level was not associated with clinical relapse. Although LRG is not an independent factor for predicting clinical relapse, the cumulative remission rate was significantly higher in patients with higher albumin than in those with lower albumin. Furthermore, the combination of FIT and albumin was useful for predicting for relapse, patients with higher FIT and lower albumin tended to have higher relapse rates than those with both lower FIT and albumin and those with lower FIT and higher albumin. Our study indicated that serum albumin level is useful for predicting relapse, even in remitting outpatients. Although LRG is not an independent factor for predicting clinical relapse, it is useful for identifying patients that are likely to relapse when combined serum albumin or FIT results.

Establishment of a Novel Colitis-Associated Cancer Mouse Model Showing Flat Invasive Neoplasia.

BACKGROUND: Chronic inflammation, such as ulcerative colitis, increases the risk of developing colitis-associated cancers. Currently, mice administered with azoxymethane/dextran sodium sulfate are well-known models for colitis-associated cancers. Although human colitis-associated cancers are often flat lesions, most azoxymethane/dextran sodium sulfate mouse cancers are raised lesions. AIMS: To establish a novel mouse model for colitis-associated cancers and evaluate its characteristics. METHODS: A single dose of azoxymethane was intraperitoneally administered to CD4-dnTGFßRII mice, which are genetically modified mice that spontaneously develop inflammatory bowel disease at different doses and timings. The morphological and biological characteristics of cancers was assessed in these mice. RESULTS: Colorectal cancer developed with different proportions in each group. In particular, a high rate of cancer was observed at 10 and 20 weeks after administration in 12-week-old CD4-dnTGFßRII mice dosed at 15 mg/kg. Immunohistochemical staining of tumors was positive for ß-catenin, ki67, and Sox9 but not for p53. Grade of inflammation was significantly higher in mice with cancer than in those without cancer (p < 0.001). In CD4-dnTGFßRII/azoxymethane mice, adenocarcinomas with flat lesions were observed, with moderate-to-severe inflammation in the non-tumor area. In comparison, non-tumor areas of azoxymethane/dextran sodium sulfate mice had less inflammation than those of CD4-dnTGFßRII/azoxymethane mice, and most macroscopic characteristics of tumors were pedunculated or sessile lesions in azoxymethane/dextran sodium sulfate mice. CONCLUSIONS: Although feasibility and reproducibility of azoxymethane/CD4-dbTGFßRII appear to be disadvantages compared to the azoxymethane/dextran sodium sulfate model, this is the first report to demonstrate that the chronic inflammatory colitis model, CD4-dnTGFßRII also develops colitis-related colorectal cancer.

Analysis of the initial dose and reduction rate of corticosteroid for ulcerative colitis in clinical practice.

Background and Aim: Trends in steroid use and the effects of the initial dose, duration of use, and tapering schedule on clinical efficacy were assessed in Japanese patients with ulcerative colitis (UC) undergoing steroid treatment. Methods: We enrolled 191 cases with UC who underwent steroid treatment between 2006 and 2020. We assessed the difference in clinical remission rates in cases with different initial doses of steroid. Clinical factors for clinical remission at week 4 and discontinuation of corticosteroid within 12 weeks were also assessed. Results: Clinical remission and response at week 4 were obtained in 107 (56.0%) and 58 cases (30.4%), respectively. In hospitalized patients, male sex (odds ratio [OR], 0.373; 95% confidence interval [CI], 0.146-0.956) and younger age (OR, 0.974; 95% CI, 0.951-0.998) were associated with clinical remission at week 4. Partial Mayo score (OR, 0.643; 95% CI, 0.451-0.918) and initial steroid dose of ≥30 mg (OR, 3.278; 95% CI, 1.274-8.435) were associated with clinical remission at week 4 in outpatients. Clinical remission at week 4 (OR, 0.300; (95% CI, 0.126-0.718)) and the steroid dose reduction rate at week 4 (OR, 0.092; 95% CI, 0.036-0.234) were associated with treatment discontinuation within 12 weeks. The proportion of patients in whom corticosteroids were discontinued at week 12 was significantly higher (P = 0.006) in 2016-2020 (28/52; 53.8%) than in 2006-2010 (15/54; 27.8%). Conclusion: The steroid reduction rate at week 4 may be critical for discontinuation within 12 weeks. Withdrawal of corticosteroids has been becoming more appropriate in the last 5 years than before.

Downregulation of MicroRNA-21 in Colonic CD3+ T Cells in UC Remission.

BACKGROUND: In active inflammatory bowel disease (IBD), microRNA expression profiling consistently features disease-specific signatures, and microRNA-21 (miR-21) has been shown to be upregulated in the inflamed colon of patients with active ulcerative colitis (UC). However, the cellular sources of miR-21 expression in IBD tissues have not yet been identified. We sought to determine the expression levels of miR-21 and one of its downstream target genes, programmed cell death 4 (PDCD4), in CD3 T cells isolated from the colonic mucosa of patients with active IBD, inactive IBD, and non-IBD controls. METHODS: Colonic biopsies were treated with collagenase V. CD3 T cells were isolated using MACS CD3 positive selection. Total RNA was converted to cDNA. Real-time PCR reactions were performed with PCR primers for miR-21, SNORD95, PDCD4, and GAPDH. RESULTS: The expression of miR-21 was statistically significantly downregulated in CD3 T cells from patients with UC in remission as compared to active disease (P = 0.0193). miR-21 negatively regulates PDCD4 expression. As predicted, the mRNA level of PCDC4 in CD3 T cells was upregulated in UC and Crohn's disease in remission as compared to active disease (UC active versus UC remission: P = 0.0008, Crohn's disease active versus Crohn's disease remission: P = 0.0215) and in patients with UC in remission as compared to healthy controls (P = 0.0226). CONCLUSIONS: Although miR-21 expression is downregulated, PDCD4 is upregulated in CD3 T cells during the remission phase of UC. Our results indicate that miR-21 and related pathways in colonic T cells may play a role in limiting pathogenic T-cell responses and may constitute future target candidates to induce remission in UC.