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Purpose The ulcerative colitis colonoscopic index of severity (UCCIS) evaluates the state of the entire colonic mucosa in ulcerative colitis. However, no cut-off values of scores for predicting clinical relapse in patients with ulcerative colitis have been established. This study aimed to determine the cut-off values for predicting clinical relapse in patients with ulcerative colitis. Methods The endoscopic scores (sum of Mayo endoscopic subscores (S-MES) and UCCIS) of 157 patients with ulcerative colitis experiencing clinical remission and their subsequent clinical course were retrospectively reviewed. The optimal cut-off values for predicting relapse and relapse-free rates were analyzed by receiver operating characteristic analysis. Results Forty patients with ulcerative colitis experienced relapse within 24 months. The median UCCIS for these patients at the time of study enrollment was significantly higher than that for patients with clinical remission (P P P = 0.004). Conclusions The data from this study indicate that the USSIC is a more relevant score than the S-MES for predicting the time to relapse in patients with ulcerative colitis in remission.

Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely understood. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to the clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for the clinical background when starting steroid treatment. The clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of the clinical activity index, the Mayo endoscopic subscore, and the UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All scores improved significantly after steroid use (P = .042, P = .002, P = .002, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistance to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.

Background Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. Methods One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0–5, 6–13, and 14–38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. Results In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0–5, 6–13, and 14–38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0–5 year disease-duration group showed particularly higher values than those for the other two groups. Conclusions Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

Background Oral tacrolimus is a therapeutic agent for moderate to severe steroid-dependent or resistant ulcerative colitis (UC), but remission induction is difficult, and it is necessary to treat the patient while considering the next treatment. Aim To examine serum albumin (Alb) level as a prognostic factor for the therapeutic effect of tacrolimus in clinical practice. Methods Forty-seven patients with UC treated with tacrolimus at our institution were divided into remission and failure groups (colectomy or switch to biologics), and the biological data at the start of observation and at weeks 1 and 2 were retrospectively examined. Kaplan-Meier and multivariate analyses were performed using Alb as a prognostic factor in UC treatment. Results During the three months observed, 17 (36.2%) patients failed treatment with tacrolimus. A comparison between the failure and remission groups showed a significant difference only in Alb in week 2, and in the week 2/week 0 Alb ratio, which showed the rate of change in Alb. The cut-off value of the week 2/week 0 Alb ratio that predicted failure was 1, and its area under the curve was 0.751 (95%CI: 0.604-0.898). In the Kaplan-Meier analysis, a week 2/week 0 Alb ratio ≤ 1 had a significantly higher failure rate than that of > 1; Cox proportional hazard regression analysis also showed that a week 2/week 0 Alb ratio ≤ 1 was an independent prognostic factor for failure within 3 mo after the start of tacrolimus treatment. Conclusion A week 2/week 0 Alb ratio ≤ 1 predicts failure within 3 mo of tacrolimus administration for UC. High failure risk exists with week 2 Alb values ≤ 1 on admission.

The fecal immunochemical occult blood test (FIT) and prostaglandin E-major urinary metabolite (PGE-MUM) have been reported to predict the relapse of ulcerative colitis (UC) during remission. In this study, we directly compared FIT and PGE-MUM in predicting relapse and examined the effect of disease duration on these biomarkers.Measurements of 2 biomarkers and endoscopic examination were performed in 73 patients with UC in remission. The patients were followed up for 12 months, and clinical relapse was evaluated. In addition, we divided the patients into long-term disease duration and short-term disease duration groups for analysis.Twenty-one patients (28.8%) relapsed within 12 months. FIT and PGE-MUM levels were significantly higher in the relapsed group than in the remission group. Cutoff values of FIT and PGE-MUM for predicting relapse using receiver operating characteristic analysis were 65.0 ng/mL (area under the curve [AUC]: 0.723) and 25.2 μg/g·Cr (AUC: 0.701), respectively. Patients with FIT ≥ 65.0 ng/mL and PGE-MUM ≥ 25.2 μg/g·Cr had a higher risk of clinical relapse. In the short-term disease duration group, the AUCs of FIT were larger than those of PGE-MUM using receiver operating characteristic analysis, in most instances. By contrast, the AUCs of PGE-MUM were larger than those of FIT in most cases in the long-term disease groups.FIT and PEG-MUM were highly accurate in predicting clinical relapse in UC patients with short and long disease durations in remission, respectively.

In 2012, Japan approved the use of a tag-less patency capsule (PC), which evaluates gastrointestinal patency before small-bowel capsule endoscopy (SBCE). This study aimed to evaluate the validity of our modification on the passage criteria for this PC in clinical practice. We retrospectively enrolled 326 consecutive patients who underwent PC examination before SBCE. If X-ray could not reveal the PC in the body during the judgement time (30–33 h after ingestion), we defined it as ‘estimated patency’ and performed SBCE. We employed plain computed tomography (CT) for the second judgement, as needed. The overall patency rate was 95.1%. By X-ray, 41 (12.6%) patients were judged to have ‘estimated patency’, and SBCE could be safely performed. Plain CT judgement was necessary in 106 patients (32.5%). One PC case had a residual coating film associated with stenosis in a patient with Crohn’s disease (CD), and one (0.3%) SBCE case had capsule retention resulting from false CT judgement. Multivariate analysis revealed that established CD and inpatient were factors related to no-patency. In conclusion, PC is useful for examining gastrointestinal patency, keeping in mind CT misjudgement. If PC was not found in the body via X-ray, performing SBCE as ‘estimated patency’ seemed appropriate.

Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC). Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported in recent years. However, the prevalence of UL97 gene mutations in GCV-naive CMV infection in the colon remains unknown. We investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for nested polymerase chain reaction (PCR) amplification of the UL97 gene. Sanger DNA sequencing was performed. In comparison with AD169 reference strain, natural polymorphisms were frequently detected in codons N68D (100%), I244V (100%), and D605E (86.4%). Seven polymorphisms were detected infrequently (

Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn’s disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4‒14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2 μg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1 μg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4–14 days after ADA administration was ≥9.2 μg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1 μg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.

We evaluated the association between endoscopic scores of colonic inflammation and fecal calprotectin (FC), fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP) in patients with ulcerative colitis (UC). Endoscopic scores reflecting the most severe lesion [maximum Mayo Endoscopic Subscore (M-MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)] and those reflecting the inflammation of the entire colon [sum of MES (S-MES) and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS)] were evaluated. FC, FIT, and CRP were measured, and their association with the four endoscopic scores was evaluated. Endoscopic scores of 78 complete colonoscopies (66 UC patients) were evaluated using the three biomarkers. FC and CRP tended to correlate more strongly with S-MES and UCCIS than with M-MES and UCEIS. In the M-MES 0, 1 group, compared to CRP, FC and FIT showed stronger correlations with S-MES and UCCIS. Conversely, in the M-MES 2, 3 group, only CRP was significantly correlated with each descriptor. CRP more strongly reflects colon-wide mucosal inflammation than FC and allows reliable assessment of inflammation throughout the colon in active UC.

Prostaglandin E-major urinary metabolite (PGE-MUM) and C-reactive protein (CRP) are useful biomarkers in patients with ulcerative colitis. However, whether changes in endoscopic scores over time are reflected in the values of these biomarkers has not been verified. This prospective observational study aimed to assess the relationship between changes in biomarker levels and endoscopic scores in patients with ulcerative colitis. A total of 100 colonoscopy intervals of patients with ulcerative colitis were enrolled. The relationship between variations in the Mayo endoscopic subscore over time and the accompanying changes in biomarker values were investigated. PGE-MUM levels showed a significant rise in the increased endoscopic score group (P = 0.007) and a decrease with reduced endoscopic score group (P = 0.023). CRP levels showed a significant decline with lower endoscopic values (P

The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) was recently reported as a new scoring system to evaluate the mucosal lesions of patients with Crohn's disease (CD). We investigated whether CECDAI is useful for assessing the necessity of early additional treatment in patients with CD in clinical remission. Twenty-one patients with small intestinal CD in clinical remission underwent capsule endoscopy (CE). The CECDAI and Lewis score (LS) were used to evaluate the intestinal lesions. We analyzed the correlations between several biomarkers and CECDAI or LS and examined the changes in therapeutic regimens based on the CECDAI. CE identified intestinal abnormalities in most CD patients in clinical remission: 81.0% and 85.7%, as assessed using CECDAI and LS, respectively. A significant positive correlation was observed between the CDAI and LS (P = .025), as well as between CDAI and CECDAI (P = .014) in these cases. Compared to LS, CECDAI scores were more evenly distributed. No significant correlations were observed between endoscopic scores and serum markers, including CRP, hemoglobin, and albumin levels. Additional treatment was performed significantly more often in patients with moderate-severe disease activity (CECDAI ≥5.8) (P = .012) than in those with normal (CECDAI

INTRODUCTION: Prostaglandin E-major urinary metabolite (PGE-MUM) is a novel biomarker reflecting endoscopic activity in ulcerative colitis (UC). However, there are no studies investigating the efficacy of PGE-MUM as a biomarker for predicting relapse. We investigated whether PGE-MUM can predict clinical relapse of UC. METHODS: The measurement of PGE-MUM and endoscopic evaluation were performed in 70 patients with UC in clinical remission. The optimal cutoff values predicting relapse and relapse-free rate were analyzed. RESULTS: Sixteen patients (22.9%) relapsed during the 12-month follow-up. The median PGE-MUM value of relapsed patients at entry was significantly higher than that of patients in clinical remission (P = 0.008). The cutoff value of PGE-MUM predicting future relapse was 25.2 μg/g Cr by receiver-operating characteristic (ROC) analysis, and the area under the ROC curve was 0.721 (95% confidence interval: 0.556–0.886). The relapse-free rate of patients with PGE-MUM ≥25.2 μg/g Cr was significantly lower than that in patients with PGE-MUM

Background The serum N-terminal telopeptide of type I collagen (NTx) is significantly higher in patients with Crohn disease (CD) than in healthy individuals and patients with ulcerative colitis. This study aimed to investigate whether an elevated serum NTx level is a risk predictor of osteoporosis in patients with CD. Methods Based on whether the femoral Z-score decreased over a 2-year period, 41 CD patients were divided into the ΔZ-score Results Although there was no correlation between the mean CDAI and the ΔZ-score, the mean serum NTx and albumin levels were significantly correlated with the ΔZ-score (P Conclusions These observations indicated that an elevated serum NTx could be a useful marker for predicting a decrease in the femoral bone mineral density in CD patients. Anti-TNF-α therapy maintained an elevated serum NTx level, suggesting that treatment with anti-TNF-α may help control increased bone resorption in CD patients.

Although the Crohn's Disease Activity Index (CDAI) is often used to evaluate the disease activity in Crohn's disease (CD), the number of liquid or soft stools cannot be precisely evaluated, and thus accurate scores cannot be calculated, in patients with enterostomy. Therefore, we created the modified CDAI (mCDAI), without the defecation frequency item from the CDAI, and examined its usefulness.Study participants comprised 9 patients with CD with enterostomy and 20 patients with CD without enterostomy. Correlations between the mCDAI and serum albumin (Alb) levels or C-reactive protein (CRP) levels were examined using regression analysis. Additionally, regression analyses were conducted in patients with CD without enterostomy to determine the Alb and CRP levels corresponding to the CDAI at its cutoff value for remission status (150). The obtained values were applied to the mCDAI regression equations to determine the equivalent mCDAI cutoff value.mCDAI and Alb levels were significantly negatively correlated (P

Decreased trough level of infliximab (TLI) is associated with diminished efficacy in patients with Crohn disease (CD). We examined whether TLI at 14 weeks subsequent to the start of infliximab (IFX) treatment would impact long-term clinical course. Serum IFX levels and antibodies to IFX (ATI) at 14 and 54 weeks after IFX administration were measured in 12 patients with mild to moderate CD. We examined patient background, clinical severity, blood test values, and the relationship between ATI and TLI up to 108 weeks. We compared the group with TLI 3 μg/mL (TLI(14) ≥ 3 group). Patients in the TLI(14) ≥ 3 group were significantly more likely to use immunomodulators before IFX treatment induction (P = .01). At 54 weeks, 2 cases of ATI production were observed in the TLI(14)

The efficacy of sustained-release preparations of mesalazine as a remission maintenance treatment for Crohn's disease remains to be established. We aimed to examine the changes in compliance rate and clinical data 2 years after switching from mesalazine tablet to granule formulation at our facility among patients with Crohn's disease in remission. We investigated the rate of continuous treatment of mesalazine granules and examined the changes in Crohn’s Disease Activity Index (CDAI) and serum C-reactive protein (CRP), albumin, and hemoglobin (Hb) levels 2 years after the switch. Compliance rate (continuous treatment vs. additional treatment) and continuous treatment rate [good (rate of ≥ 70%) vs. poor (rate P = 0.023) and Hb levels increased significantly (P = 0.002). No change in the compliance rate was found. Our results suggest that mesalazine granule formulation may have a remission maintenance effect that is superior to that of mesalazine tablets.

Purpose: The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP).Methods: We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger’s clinical activity index (CAI) of ≤4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤1.Results: FIT results were significantly correlated with all activity scores when the disease duration was

Background Prostaglandin E-major urinary metabolite (PGE-MUM) may be a novel biomarker for evaluating disease activity in ulcerative colitis (UC). We compared its usefulness to that of the fecal immunochemical occult blood test (FIT). Methods PGE-MUM and FIT measurements were performed of 92 urinary and fecal samples obtained from 60 patients with UC. Endoscopic activity was determined by Mayo endoscopic subscore (eMayo) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. Results PGE-MUM levels and FIT results showed a significant correlation with respect to eMayo (P P P = 0.012). Both biomarkers were significantly correlated with the UCEIS score (P P P = 0.012). PGE-MUM and FIT were significantly correlated with eMayo in the group with a disease duration P = 0.041 and P P = 0.012), FIT was not correlated with eMayo (P = 0.101). Conclusions PGE-MUM is useful as a biomarker as FIT for evaluating the endoscopic activity, particularly in long-term affected patients with UC.