Toshihiro Inokuchi

Evaluation of Mucosal Healing in Ulcerative Colitis by Fecal Calprotectin Vs. Fecal Immunochemical Test.

OBJECTIVES:We previously showed that a quantitative fecal immunochemical test (FIT) can predict mucosal healing (MH) in ulcerative colitis (UC). Fecal calprotectin (Fcal) has also been reported as an important biomarker of UC activity. The aim of this study was to compare the predictive ability of these two fecal markers for MH in UC.METHODS:FIT and Fcal were examined in stool samples from consecutive UC patients who underwent colonoscopy. Mucosal status was assessed via the Mayo endoscopic subscore (MES).RESULTS:In total, 105 colonoscopies in 92 UC patients were evaluated in conjunction with the FIT and Fcal results. Both FIT and Fcal results were significantly correlated with MES (Spearman’s rank correlation coefficient: 0.61 and 0.58, respectively). The sensitivity and specificity of the FIT values (<100 ng/ml) for predicting MH (MES 0 alone) were 0.95 and 0.62, respectively, whereas those of Fcal (<250 μg/g) were 0.82 and 0.62, respectively. The sensitivities became similar when MH was defined as MES 0 or 1 (0.86 vs. 0.86). Although the predictability of MH evaluated by the area under the receiver operating characteristics curve was similar for the two fecal markers (FIT 0.83 vs. Fcal 0.82 for MES 0 alone), the FIT results were relatively robust regardless of the cutoff value selected.CONCLUSIONS:Both FIT and Fcal can efficiently predict MH in UC, but FIT appears to be more sensitive than Fcal for predicting MES 0 alone.

Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count.

AIM To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1. METHODS UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES. Parameters, including blood tests, to identify predictive factors for MES 0 and slight endoscopic recurrence in clinically stable patients were assessed. Moreover, a receiver operating characteristic curve was generated, and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing. All P values were two-sided and considered significant when less than 0.05. RESULTS A total of 183 patients with clinical remission were examined. Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P < 0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with MES 1 vs MES 0 was 8.17 (95%CI: 4.19-17.96, P < 0.0001). The platelet count (PLT) < 26 × 10(4)/μL was an independent predictive factor for complete mucosal healing (OR = 4.1, 95%CI: 2.15-7.99). Among patients with MES 0 at the initial colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0 (3.8 × 10(4)/μL vs -0.6 × 10(4)/μL, P < 0.0001). CONCLUSION The relapse rate differed greatly between patients with complete and partial mucosal healing. A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT.

Fecal Immunochemical Test Versus Fecal Calprotectin for Prediction of Mucosal Healing in Crohn's Disease

Background:Mucosal healing (MH) has been proposed as a treatment goal of inflammatory bowel disease patients. We reported recently that not only fecal calprotectin (Fcal) but also the fecal immunochemical test (FIT) can predict MH in ulcerative colitis. However, the predictive power of the fecal markers for MH in Crohns disease (CD), particularly with small bowel lesions, has not been reported in detail. The aim of this study was to evaluate the predictability of FIT versus Fcal for MH in CD. Methods:Consecutive CD patients underwent colonoscopy or balloon-assisted enteroscopy according to the disease location. FIT and Fcal were examined using stool samples collected the day before endoscopy. Results:Seventy-one CD patients were analyzed, of whom 42 (59%) underwent balloon-assisted enteroscopy because of the presence of affected lesions in the small intestine. Both the Fcal and the FIT results were significantly correlated with endoscopic activity (r = 0.67 and 0.54, respectively). However, the FIT results did not correlate with the activity in patients with small bowel lesions alone, whereas Fcal did (r = 0.42 versus 0.78). Fcal predicted MH in CD with 87% sensitivity and 71% specificity, whereas the values for FIT were 96% and 48%, respectively. The specificity for MH among patients with small bowel lesions alone was low for FIT (40%) compared with Fcal (80%). Conclusions:Both FIT and Fcal were correlated with the mucosal status of CD. However, the specificity of FIT was not satisfactory, particularly for small bowel lesions.

Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin?

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohns disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse

AIM To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results. METHODS The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results. RESULTS Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23). CONCLUSION Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status

AIM To clarify the impact of cytomegalovirus (CMV) activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis (UC) patients. METHODS UC patients with flare-up were divided into CMV-positive and -negative groups according to the CMV antigenemia assay. The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir. RESULTS The median number of days to initial remission was significantly greater for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However, the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups. Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group. CONCLUSION CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

Consecutive Measurements by Faecal Immunochemical Test in Quiescent Ulcerative Colitis Patients Can Detect Clinical Relapse.

BACKGROUND We have reported that results of the quantitative faecal immunochemical test (FIT; haemoglobin concentrations in faeces measured using an antibody for human haemoglobin) effectively reflect the mucosal status of ulcerative colitis (UC). The aim of this study was to evaluate the predictability of flare-up in quiescent UC patients by consecutive FIT evaluation. METHODS Patients with UC who fulfilled the following criteria by index colonoscopy were enrolled: clinical remission; mucosal healing (Mayo endoscopic subscore 0); and negative FIT (less than 100ng/mL). These patients were followed up prospectively every 1-3 months by monitoring patient symptoms and FIT results between index and subsequent colonoscopies. RESULTS The intervals between 2 colonoscopies (median 2.51 years) of 83 patients (49 males, median age at onset 34 years, median disease duration 9.74 years) were analysed. None of the 43 (52%) patients who maintained negative FIT throughout the observation period exhibited clinical relapse. On the other hand, 25/40 (63%) patients who showed positive conversion of FIT during the period experienced relapse. The cutoff FIT value of 450ng/mL could predict relapse with 73% positive predictive value and 96% negative predictive value. Moreover, positive conversion of FIT preceded occurrence of symptoms by 1 month or more in nearly one-third of patients with relapse. CONCLUSIONS Consecutive measurements of FIT in quiescent UC patients who achieved mucosal healing with negative FIT would help identify patients with clinical relapse whose symptoms had not yet presented. Further investigations are required for more precise prediction of relapse with this modality.

A Randomized Trial of Monopolar Soft-mode Coagulation Versus Heater Probe Thermocoagulation for Peptic Ulcer Bleeding.

Background and Aim: Endoscopic therapy has been demonstrated to be effective in achieving hemostasis for bleeding peptic ulcers. Thermal coagulation is one of the most commonly used methods, with a high success rate. Recently, endoscopic submucosal dissection for early gastric carcinoma was developed and hemostasis with soft coagulation using hemostatic forceps was introduced. The aim of this study was to compare the hemostatic efficacy of soft coagulation with heater probe thermocoagulation for peptic ulcer bleeding. Methods: Patients who visited our hospital with hematemesis or melena underwent emergency endoscopy. Inclusion criteria were presentation with an actively bleeding ulcer, a nonbleeding visible vessel, or an adherent clot. Patients were excluded if they were unwilling to give written informed consent or had a bleeding gastric malignancy. Patients were randomized to receive endoscopic hemostasis with soft coagulation (Group S) or heater probe thermocoagulation (Group H). The primary endpoint was the primary hemostasis rate and secondary endpoints were rebleeding rate, complications, and the procedure time. Results: Between May 2010 and February 2012, a total of 111 patients (89 gastric ulcers and 22 duodenal ulcers) were enrolled. Primary hemostasis was achieved in 54 patients (96%) in Group S and 37 (67%) in Group H (P<0.0001). Rebleeding occurred in 7 patients in Group H and none in Group S. Of these 7 patients, urgent surgery was performed in 1. Perforation occurred in 2 patients in Group H, which was managed conservatively. Conclusions: For patients with gastroduodenal ulcer bleeding, soft coagulation using monopolar hemostatic forceps is more effective than heater probe thermocoagulation for achieving hemostasis.

Clinical outcome of patients with obscure gastrointestinal bleeding during antithrombotic drug therapy

Background: The clinical outcome of patients with obscure gastrointestinal bleeding (OGIB) during antithrombotic drug therapy has not been fully investigated. Methods: Patients who underwent video capsule endoscopy (VCE) for the investigation of OGIB at Okayama University Hospital from January 2009 to March 2016 were enrolled. We evaluated the VCE findings, the patterns of OGIB, and the rate of rebleeding within 1 year in antithrombotic drug users and antithrombotic drug nonusers. Results: A total of 181 patients were enrolled. Among the antithrombotic drug users, the rate of VCE positivity in the patients with overt OGIB was significantly higher in comparison with patients with occult OGIB (45% versus 16%, p = 0.014), whereas there was no significant difference among the antithrombotic drug nonusers (27% versus 26%, p = 1.0). Among the antithrombotic drug users, the rate of rebleeding among the VCE-positive patients was significantly higher in comparison with the VCE-negative patients (50% versus 5.9%, p = 0.011). Moreover, among antithrombotic drug users who did not receive therapeutic intervention, the rate of rebleeding among the VCE-positive patients was significantly higher in comparison with the VCE-negative patients (75% versus 6.3%, p = 0.001). However, among the antithrombotic drug nonusers who did not receive therapeutic intervention, the rebleeding rate of the VCE-positive patients was not significantly different from that of the VCE-negative patients (20% versus 9.4%, p = 0.43). Conclusion: Therapeutic intervention should be considered for patients with overt OGIB who are VCE positive and who use antithrombotic drugs due to the high risk of rebleeding.

Simultaneous Measurements of Faecal Calprotectin and the Faecal Immunochemical Test in Quiescent Ulcerative Colitis Patients Can Stratify Risk of Relapse

Background Both faecal calprotectin [Fcal] and the faecal immunochemical test [FIT] are useful to predict clinical relapse of ulcerative colitis [UC]. However, the difference between Fcal and FIT in ability to predict relapse has scarcely been reported. Whether the combined use of these two faecal markers increases the predictability is also unknown. Methods UC patients in clinical remission who underwent colonoscopy were enrolled prospectively, and the Fcal and FIT values were examined at enrolment. Their clinical course was observed for 2 years or until relapse. The correlation between the incidence of relapse and the values of the two markers was examined. Results A total of 113 patients were enrolled, and 48 [42%] relapsed. Fcal ≥ 75 μg/g and FIT ≥ 110 ng/mL were defined as Fcal-positive and FIT-positive, respectively, according to the receiver operating characteristic curves. Both Fcal-positive and FIT-positive statuses were independent predictive factors of clinical relapse (hazard ratio [HR] 2.29; 95% confidence interval [CI], 1.23-4.49; p = 0.0086, and HR 2.91; 95% CI, 1.49-5.50; p = 0.0022, respectively). Categorisation of patients into three groups according to the faecal marker status [FIT-positive, FIT-negative and Fcal-positive, and both negative] can efficiently stratify the risk of relapse with graded increases in risk [FIT-negative and Fcal-positive: HR 2.05; 95% CI, 1.02-4.43; p = 0.0045, and FIT-positive: HR 5.43; 95% CI, 2.57-11.76; p < 0.0001, compared with both negative]. Conclusions Fcal vs FIT showed distinct properties regarding the prediction of relapse in UC. A risk assessment using both faecal markers could increase the predictability for relapse.