Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. METHODS: Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. RESULTS: MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. CONCLUSIONS: MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis.

Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis.

BACKGROUND: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. AIM: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. METHODS: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. RESULTS: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. CONCLUSION: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy.

High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma.

BACKGROUND/AIM: DNA damage response (DDR), wherein p21 is a cell fate determinant, is a potential cancer therapeutic target. Molecular expression during DDR was explored in ovarian clear-cell carcinoma (CCC). MATERIALS AND METHODS: CHK1, CHK2, TP53 and p21 expression in DDR was examined using immunostaining in surgical sections of CCC (n=22). Molecular alterations in two types of CCC cell lines, JHOC-5 and JHOC-9, were investigated using western blot analysis. RESULTS: Expression of DDR-associated molecules was noted in most patients. While high p21 expression was found in half of the patients, the remaining patients exhibited low p21 expression. Treatment with UC2288, a p21 inhibitor, attenuated proliferation of both cell lines, more prominently in JHOC-9, resulting in reduced viability and subsequent apoptosis. CONCLUSION: p21 Inhibitor induced cell death in cells with high p21 expression, suggesting that p21 suppression can be a therapeutic strategy to treat patients with CCC.

Effects of L-Menthol and Carbon Dioxide on the Adenoma Detection Rate during Colonoscopy: L-Menthol and Carbon Dioxide on Colonoscopy.

BACKGROUND AND AIMS: We examined the efficacy of the combined use of L-menthol spraying (L-mentholS) as an antispasmodic agent and carbon dioxide insufflation (CO2I) on the adenoma detection rate (ADR) in a prospective, single-center trial with a 2 × 2 factorial design. METHODS: We randomly assigned 611 patients scheduled to undergo colonoscopy to 4 groups: (1) the L-mentholS + CO2I (n = 153), (2) L-mentholS + air insufflation (AI; n = 156), (3) CO2I (n = 153), and (4) AI (n = 149) groups. We used 20 mL of 0.8%-L-menthol solution for the L-mentholS. The primary outcome was the difference in the ADR, and the secondary outcomes were the differences in colonic peristalsis and abdominal pain. -Results: The ADRs were not different among the groups: 1/2/3/4; 39.9%/43.6%/41.2%/51.0%. CO2I was associated with a significant decrease in the ADR (OR 0.57; 95% CI 0.35- 0.93) with a multiple logistic regression. The interaction between L-mentholS and CO2I was associated with a suppression of the decrease in the ADR. Both L-mentholS and CO2I were associated with a significant decrease in abdominal pain, and L-mentholS was associated with a significant improvement of peristalsis. CONCLUSIONS: The fact that CO2I was associated with significant decreases in the ADR was a problem. The combined use of L-mentholS and CO2I could help to suppress the decrease in the ADR.