scholarly journals P148 Reproducibility of PICaSSO score by using narrow banding images (NBI) to assess mucosal and histological healing in ulcerative colitis (UC) patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S211-S212 ◽  
Author(s):  
R Cannatelli ◽  
O Nardone ◽  
U Shivaji ◽  
S C L Smith ◽  
A Bazarova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Roc Curves ◽  
Mucosal Healing ◽  
Operating Characteristics ◽  
Mayo Score ◽  
Endoscopic Remission ◽  
Histological Activity ◽  
Index Of Severity ◽  
Virtual Chromoendoscopy ◽  
Sensitivity Specificity

Abstract Background The endoscopic and histological healing are key therapeutic targets in ulcerative colitis(UC) patients. PICaSSO (Paddington International virtual ChromoendoScopy ScOre)1,2 is a new Virtual Chromoendoscopy Endoscopic (VCE) score to better define mucosal healing by mucosal and vascular features. Originally validated using iSCAN platform, the aim of this study was to evaluate the reproducibility of PICaSSO with NBI near focus platform and to assess if this could predict histological healing. Methods We prospectively studied 78 UC patients (mean age 43.4 years, 52.6% male) who underwent colonoscopy for colitis assessment or surveillance using NBI near focus (Olympus, Japan). Endoscopic activity was assessed by using ulcerative colitis Endoscopic Index of Severity (UCEIS) and PICaSSO; whilst histological activity was scored by the Robarts Histology Index (RHI). ROC curves were performed to evaluate sensitivity, specificity and accuracy of endoscopy scores to predict histological healing. Results Out of 78 patients, 47 (60.3%) were in clinical remission according to the partial Mayo score. 28(35.9%) and 32(41.0%) were in endoscopic remission according to UCEIS≤1 and PICaSSO≤3, respectively. The best cut-off of UCEIS to predict histological healing was less or equal to 1. Sensitivity, specificity and accuracy were 84.6% (95% CI 63.5, 96.4), 88.5% (95% CI 70.1, 97.8) and 87.2% (95% CI 75.6, 93.6), respectively. The Area Under the ROC curve (AUROC) was 93.3% (95% CI 88.2, 98.3). The best threshold of PICaSSO in the prediction of histological healing was less or equal to 3. PICaSSO ≤ 3 have sensitivity of 96.2% (95% CI 76.9, 100), specificity of 86.5% (95% CI 67.3, 96.2) and accuracy of 89.7% (95% CI 77.6, 96.2) to predict histological healing, estimated as RHI ≤ 3. The AUROC was 95.3% (95% CI 91.1, 99.5). Conclusion PICaSSO VCE score can be easily and accurately reproduced with NBI near focus platform and it has better operating characteristics than UCEIS to predict histological healing defined by RHI. Reference

scholarly journals P227 Defining faecal calprotectin thresholds to predict endoscopic and histological healing in ulcerative colitis (UC) by using advanced optical enhancement techniques

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S255-S256
Author(s):  
R Cannatelli ◽  
D Zardo ◽  
O Nardone ◽  
A Bazarova ◽  
U Shivaji ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Surrogate Marker ◽  
Scoring Systems ◽  
Roc Curves ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
Area Under Roc Curve ◽  
Index Of Severity ◽  
Sensitivity Specificity ◽  
A Prospective Study

Abstract Background Faecal calprotectin (FC) is the most common surrogate marker of mucosal healing (MH) in UC. A number of endoscopic and histologic scoring systems in UC have been developed for defining MH. We report the optimum FC thresholds for defining MH using all the assessment methods. Methods In a prospective study we collected all clinical, endoscopic and histologic data and FC from 76 UC patients (mean age 44.2y, 50.0% male) who attended endoscopy unit for colitis assessment or surveillance. Endoscopic scores were determined by the same endoscopist (MI) and included Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and PICaSSO (Paddington International virtual ChromoendoScopy ScOre). Histological activity was scored by the Robarts Histology Index (RHI) and Nancy Index by the same pathologist (DZ). Faecal calprotectin was assayed using Buhlmann faecal turbo test, particle enhanced turbidimetric immunoassay. ROC curves were performed to evaluate sensitivity, specificity and accuracy of the optimum cut-off of FC to predict endoscopic and histological healing. Results The best cut-off for FC to predict endoscopic healing calculated as Picasso≤3 was 161 μg/g with Area Under ROC curve (AUROC) of 85.3% (95% CI 76.2, 94.4). Sensitivity, specificity and accuracy were 87.9% (95% CI 57.6, 100), 76.7% (95% CI 53.5, 90.7) and 81.6% (95% CI 68.4, 89.5), respectively. While, the best threshold of FC to predict UCEIS≤1 was 148 μg/g with AUROC of 89.2 (95% CI 81.9, 96.5). Sensitivity was 93.5% (95% CI 50.5, 100), specificity 82.2% (95% CI 53.3, 91.1) and accuracy 86.8% (95% CI 69.7, 92.1). The best threshold for FC to predict MES equal to 0, was 112 μg/g, with AUROC of 89.6 μg/g, (95% CI 82.5, 96.7). Sensitivity, specificity and accuracy were 89.7%ww (95% CI 39.2, 100), 85.1% (95% CI 55.3, 93.6) and 86.9% (95% CI 68.4, 92.1), respectively. The best value of FC to predict histological healing with RHI≤3 was 112μg/g with AUROC of 88.0% (95% CI 80.6, 95.4). Sensitivity, specificity and accuracy were 88.5% (95% CI 53.8, 100), 80.0% (95% CI 62.0, 90.0) and 82.9% (95% CI 72.5, 89.5), respectively. When used Nancy≤1 FC cut-off to predict healing was 172 μg/g with AUROC of 87.1% (95% CI 78.6, 95.6). Sensitivity was 96.4% (95% CI 60.7, 100), specificity 72.9% (54.2, 85.4) and accuracy 81.6% (69.7, 89.5). Conclusion Advanced enhancement technologies can accurately define the level of FC to predict endoscopic and histological healing in UC. The optimum FC threshold for MH by PICaSSO and by Nancy was similar (161 and 172 μg/g respectively), while the FC threshold for mucosal healing by MES and by RHI was 112 μg/g. The FC threshold for determining MH in clinical practice should be lower than at least 200 μg/g.

Assessment of Endoscopic Healing by Using Advanced Technologies Reflects Histological Healing in Ulcerative Colitis

2020 ◽  
Vol 14 (9) ◽  
pp. 1282-1289 ◽  
Author(s):  
Marietta Iacucci ◽  
Rosanna Cannatelli ◽  
Xianyong Gui ◽  
Davide Zardo ◽  
Alina Bazarova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Roc Curves ◽  
Mucosal Healing ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
High Definition ◽  
Endoscopic Score ◽  
Virtual Chromoendoscopy ◽  
Sensitivity Specificity ◽  
A Prospective Study

Abstract Background Several studies have reported that ulcerative colitis [UC] patients with endoscopic mucosal healing may still have histological inflammation. We investigated the relationship between mucosal healing defined by modified PICaSSO [Paddington International Virtual ChromoendoScopy ScOre], Mayo Endoscopic Score [MES] and probe-based confocal laser endomicroscopy [pCLE] with histological indices in UC. Methods A prospective study enrolling 82 UC patients [male 66%] was conducted. High-definition colonoscopy was performed to evaluate the activity of the disease with MES assessed with High-Definition MES [HD-MES] and modified PICaSSO and targeted biopsies were taken; pCLE was then performed. Receiver operating characteristic [ROC] curves were plotted to determine the best thresholds for modified PICaSSO and pCLE scores that predicted histological healing according to the Robarts Histopathology Index [RHI] and ECAP ‘Extension, Chronicity, Activity, Plus’ histology score. Results A modified PICaSSO of ≤ 4 predicted histological healing at RHI ≤ 3, with sensitivity, specificity, accuracy and area under the ROC curve [AUROC] of 89.8%, 95.7%, 91.5% and 95.9% respectively. The sensitivity, specificity, accuracy and AUROC of HD-MES to predict histological healing by RHI were 81.4%, 95.7%, 85.4% and 92.1%, respectively. A pCLE ≤ 10 predicted histological healing with sensitivity of 94.9%, specificity of 91.3%, accuracy of 93.9% and AUROC of 96.5%. An ECAP of ≤ 10 was predicted by modified PICaSSO ≤ 4 with accuracy of 91.5% and AUROC of 95.9%. Conclusion Histological healing by RHI and ECAP is accurately predicted by HD-MES and modified virtual electronic chromoendoscopy PICaSSO, endoscopic score; and the use of pCLE did not improve the accuracy any further.

scholarly journals Effectiveness of treatment of moderate ulcerative colitis with prolonged mesalazine in real clinical practice

2021 ◽  
pp. 144-151
Author(s):  
O. V. Knyazev ◽  
A. V. Kagramanova ◽  
A. A. Lishchinskaya
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Topical Therapy ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Prolonged Release ◽  
Mayo Score ◽  
Endoscopic Remission ◽  
Oral Mesalazine ◽  
High Doses

Introduction. Ulcerative colitis (UC) is one of the severe therapeutic diseases. High doses of oral granular mesalazine are required to maintain clinical and endoscopic remission of UC, which may be sufficient and supposedly more acceptable for patients, as some studies showed that adherence to topical therapy is significantly lower than to oral 5-ASA drugs.Objective of the study. To evaluate the efficacy of therapy of patients with moderate left-sided ulcerative colitis (UC) and pancolitis receiving prolonged-release ethylcellulose-coated mesalazine.Materials and methods. The evaluation of the outcomes of treatment of UC patients who received prolonged-release mesalazine was carried out. We examined 87 patients with UC who received granular ethylcellulose-coated mesalazine, of those 38 (43.7%) men and 49 (56.3%) women. The average age of the enrolled patients was 38.3 ± 12.6 years.Results and discussion. After 2 weeks from the beginning of therapy with prolonged-release mesalazine, the majority of patients – 71 (81.6%) responded to the therapy. After 12 weeks, 71 (81.6%) of 87 UC patients, who responded to therapy with prolongedrelease mesalazine, remained in clinical remission. On average, the Mayo score in the group decreased from 7.6 ± 0.99 to 2.6 ± 0.25 points. There was a significant decrease in CRP, ESR, leukocytosis, and fecal calprotectin. After 26 weeks, Mayo score in the group of patients remained on average at the level of 2.2–2.3 points. The number of UC patients with colon mucosal healing was 32 (36.8%) patients. A year after the start of therapy with prolonged-release mesalazine, 69 (79.3%) UC patients who responded to therapy had a clinical remission, of those 32 (36.8%) patients had a clinical and endoscopic remission. During the year of observation, no case of surgical intervention or re-hospitalization due to exacerbation of the disease was recorded in patients with UC who achieved remission.Conclusions. Treatment of moderate active UC should begin with oral mesalazine ≥ 3 g per day in combination with topical mesalazine. The prolonged-release mesalazines are the most preferred

scholarly journals Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis

2019 ◽  
Vol 26 (11) ◽  
pp. 1722-1729 ◽  
Author(s):  
David Kevans ◽  
Richard Kirsch ◽  
Callum Dargavel ◽  
Boyko Kabakchiev ◽  
Robert Riddell ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mucosal Healing ◽  
Mucosal Inflammation ◽  
Clinical Relapse ◽  
Disease Relapse ◽  
Mayo Score ◽  
Therapeutic Decisions ◽  
First Relapse ◽  
Histological Activity

Abstract Background In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC. Methods Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy. Results Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2–118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse. Conclusions In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC.

scholarly journals Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients

2017 ◽  
Vol 24 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Gheorghe Hundorfean ◽  
Mircea T Chiriac ◽  
Sidonia Mihai ◽  
Arndt Hartmann ◽  
Jonas Mudter ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
High Sensitivity ◽  
Mucosal Healing ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Mayo Score ◽  
Before And After ◽  
Sensitivity Specificity ◽  
Development And Validation

Abstract Background Endoscopic monitoring is fundamental for evaluating the therapeutic response in IBD, but a validated endomicroscopic mucosal healing (MH) score is not available to date. However, confocal laser endomicroscopy (CLE) might define MH more precisely than conventional endoscopy. The major aim was to establish and validate an MH score for ulcerative colitis (UC), based on CLE. Methods In an initial pilot study (n = 10), various CLE changes were analyzed for identification of reproducible criteria for establishing a CLE score. Four reproducible CLE criteria were implemented in a following validation study. Subsequently, active UC patients (n = 23, Mayo score ≥6) were prospectively included and underwent colonoscopy with CLE before and after 3 anti-TNF applications. Patients were clinically followed over a period of 3 years. The endomicroscopic MH score (eMHs; range, 0–4) was compared with histopathology and endoscopy scores from the same colonic location. Results The eMHs showed high sensitivity, specificity, and accuracy values (100% with 95% confidence interval [CI] of 15.81%–100%; 93.75% with 95% CI of 69.77%–99.84%, and 94.44%, respectively). The eMHs showed a good correlation with the histological Gupta score (rs = 0.82, P < 0.0001) and the endoscopic Mayo subscore (rs = 0.81%, P < 0.0001). Sixty percent of therapy responders presented an eMHs <1, which translated into long-lasting clinical remission and reduced hospitalization, steroid, and surgery need. Conclusions CLE can accurately assess MH based on the newly developed and statistically validated eMHs in UC, and it is superior in predicting the long-lasting clinical outcome based on both descriptive and functional barrier imaging (NCT01417728).

scholarly journals Predictive values of stool-based tests for mucosal healing among Taiwanese patients with ulcerative colitis: a retrospective cohort analysis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9537
Author(s):  
Hsu-Heng Yen ◽  
Mei-Wen Chen ◽  
Yu-Yao Chang ◽  
Hsuan-Yuan Huang ◽  
Tsui-Chun Hsu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Marker ◽  
Symptom Relief ◽  
Cohort Analysis ◽  
Mucosal Healing ◽  
Asia Pacific ◽  
Fecal Occult Blood ◽  
Operating Characteristics ◽  
Predictive Values ◽  
Mayo Score

Background/Purpose Over the past two decades, ulcerative colitis (UC) has emerged in the Asia Pacific area, and its treatment goal has shifted from symptom relief to endoscopic remission. Endoscopy is the gold standard for the assessment of mucosal healing; however, it is an invasive method. Fecal calprotectin (FC) is a non-invasive stool-based inflammatory marker which has been used to monitor mucosal healing status, but it is expensive. By contrast, the immune fecal occult blood test (iFOBT) is a widely utilized stool-based screening tool for colorectal cancer. In this study, we compared the predictive values of iFOBT and FC for mucosal healing in Taiwanese patients with UC. Methods A total of 50 patients with UC identified via the electronic clinical database of Changhua Christian Hospital, Taiwan, were retrospectively enrolled from January 2018 to July 2019. Results of iFOBT, FC level, and blood tests as well as Mayo scores were reviewed and analyzed. Colonic mucosa was evaluated using the endoscopic Mayo subscore. Results The average age of the patients was 46 years, and 62% of the patients were men. Disease distribution was as follows: E1 (26%), E2 (40%), and E3 (34%). Complete mucosal healing (Mayo score = 0) was observed in 30% of patients. Endoscopic mucosal healing with a Mayo score of 0 or 1 was observed in 62% of the patients. Results of FC and iFOBT were compared among patients with and without mucosal healing. Predictive cutoff values were analyzed using receiver operating characteristics curves. iFOBT and FC had similar area under the curve for both complete mucosal healing (0.813 vs. 0.769, respectively, p = 0.5581) and endoscopic mucosal healing (0.906 vs. 0.812, respectively, p = 0.1207). Conclusion In daily clinical practice, FC and iFOBT do not differ in terms of predictive values for mucosal healing among Taiwanese patients with UC.

scholarly journals P310 The efficacy of linked colour imaging, a novel endoscopic enhancement system, for diagnosing mucosal redness in ulcerative colitis patients in clinical remission

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S309-S309
Author(s):  
T Takagi ◽  
K Uchiyama ◽  
M Kajiwara ◽  
Y Azuma ◽  
S Takayama ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Colonic Mucosa ◽  
Mucosal Healing ◽  
Time Interval ◽  
Histological Activity ◽  
Index Of Severity ◽  
Long Term Prognosis ◽  
Linked Color Imaging ◽  
Relapse Rates

Abstract Background Endoscopic mucosal healing is considered as an important therapeutic goal in ulcerative colitis (UC) patients, and several endoscopic evaluations for colonic mucosa such as Mayo endoscopic subscore (MES) and Colitis Endoscopic Index of Severity (UCEIS) are used in clinical practice. Though the strict mucosal healing is defined as MES 0, the relapse of UC has been shown in the patients diagnosed as MES 0. In the present study, we aimed to investigate the efficacy of Linked Color Imaging (LCI), a novel endoscopic enhancement system, to predict long-term prognosis in UC patients diagnosed with MES 0. Methods Twenty-six patients with UC in clinical remission and diagnosed with MES 0 were enrolled. Endoscopic colonic images were assessed by LCI and UCEIS, using a LASEREO endoscopic system (FUJIFILM Co., Tokyo, Japan). Endoscopic LCI images were classified into three subgroups by LCI classification as previously reported. Briefly, LCI patterns were classified as A, no redness; B, redness with visible vessels; and C, redness without visible vessels. Forty months was defined as the time interval between endoscopic diagnosis and relapse of UC. Histological activity was scored according to the Geboes’ score (GS) and the active mucosa was defined by GS>2B.1. Results LCI classification can further subdivide the colonic mucosa diagnosed as MES 0. The patients with LCI-A showed no relapse and the non-relapse rates compared with the patients with LCI-B showed significantly higher (p = 0.033), while the relapse rates of the patients with UCEIS 0 showed no difference compared with UCEIS 1 (p = 0.148). There was no statistical difference in the composition of LCI-A and relapse rate between active and inactive mucosa diagnosed by GS score. Conclusion Endoscopic LCI classification can further subdivide samples diagnosed MES 0. LCI can be a novel and surpassing approach to evaluate mucosal healing and predict the outcome in UC patients.

scholarly journals P532 Measuring endoscopic activity in patients treated with vedolizumab for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S455-S456
Author(s):  
C EMONT ◽  
C Gay ◽  
A L Parmentier ◽  
S Koch ◽  
S Ambregna ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Logistic Regression ◽  
Prospective Cohort ◽  
Real Life ◽  
First Trimester ◽  
Mucosal Healing ◽  
Specific Pattern ◽  
Mayo Score ◽  
Treatment Optimisation ◽  
Endoscopic Remission

Abstract Background Vedolizumab (VDZ) has proven its efficacy in ulcerative colitis (UC). The delay to obtain endoscopic remission with anti-α4β7 integrin is unclear. We aimed to assess the potential of VDZ to induce endoscopic remission and its characteristics in real-life settings. Methods We conducted a pooled analysis with prospective and retrospective data of patients who started VDZ for an active UC in two French hospitals. Patients underwent proctosigmoidoscopies at baseline and at weeks 14, 30 and 54 in the prospective cohort. A central blinded review of all endoscopy recordings was performed by two experts, pooled with some recordings from anti-TNFɑ treated patients. The primary endpoint was the proportion of patients in endoscopic remission (endoscopic Mayo score (eMs) ≤ 1) within 54 weeks. Secondary endpoints included the description of the pattern of mucosal healing and the evolution of UC activity. Characteristics of endoscopic remitters and non-remitters were compared and predictive factors of endoscopic remission were reported in univariate logistic regression. Results Forty-two patients were enrolled, 22 in the prospective cohort and 20 in the retrospective cohort. At baseline, 38 (90.5%) patients had previously experienced anti-TNFɑ, 14 (33.3%) were treated with corticosteroids and 15 (35.7%) with immunosuppressors. Twenty-six (61.9%) patients achieved endoscopic remission after a median time of 14 weeks. Endoscopic response and histologic remission occurred in 27 (64.3%) and 21 (50%) patients within 54 weeks, respectively. No specific pattern of mucosal healing was found with VDZ as compared with anti-TNFɑ treated patients. UC activity steady improved over time. Endoscopic remitters had a lower disease activity at baseline (total Mayo score (tMs) 8.1 vs. 9.5, p = 0.007; UCEIS 4.3 vs. 5.6, p = 0.0005; Nancy’s score 2.8 vs. 3.6, p = 0.004) and at week 14 (tMs 3 vs. 6, p = 0.001; eMs 1.3 vs. 2.5, p = 0.005; UCEIS 2.7 vs. 5.4, p = 0.0007; Nancy’s score 2.2 vs. 3.6, p = 0.001) and needed less treatment optimisation (11.5 vs. 81.3%, p < 0.0001) than non-remitters. In univariate logistic regression, predictors of no endoscopic remission were a high endoscopic activity at baseline (eMs > 2, OR 0.2 IC 95% 0.05–0.86, p = 0,021; UCEIS > 5 OR 0.22 IC 95% 0.06–0.84, p = 0.022) and treatment optimisation (OR 0.03; IC 95% 0.01–0.17, p < 0.001). Conclusion In our series, about two-thirds of UC refractory patients achieved endoscopic remission during the first year. Endoscopic healing was early reported, in half of patients at the end of the first trimester, actually suggesting a rather fast mechanism of action of VDZ on mucosal healing. Baseline UC activity impacted endoscopic remission.

scholarly journals OP28 Gene expression (GE) values in a phase 2 trial of mirikizumab in ulcerative colitis (UC) correlate better with histopathology (HP) than endoscopy (EN) and Mayo scores

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S025-S026
Author(s):  
B Steere ◽  
K GOTTLIEB ◽  
J Schmitz ◽  
R Higgs ◽  
B Jia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Simulation Analysis ◽  
Mucosal Healing ◽  
P Value ◽  
Pathway Network ◽  
Phase 2 Trial ◽  
Mayo Score ◽  
Index Of Severity ◽  
Regulated Gene Expression

Abstract Background HP is considered integral to the definition of mucosal healing of UC. The regulated transcription of genes determines cell identity and function, and, consequentially, HP and EN appearance. Here we correlate GE in a UC clinical trial with EN and HP indices, and the modified Mayo score (MMS). Methods 249 patients. with moderately-to-severely active UC were randomised to placebo or different doses of mirikizumab, a p19-directed IL-23 antibody (NCT02589665). Gene expression in baseline biopsy samples from the most affected area in the colon was evaluated using Affymetrix HTA2.0 exon-format microarray with a typical Bioconductor workflow (DOI: 10.1186/gb-2004-5-10-r801). Genes were represented by their largest groups of highly correlated exon groups. Expression values were correlated with Robart‘s Histopathology Index (RHI), Geboes score (GS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and modified Mayo score (MMS) at baseline. A threshold of false-discovery rate (FDR)-adjusted p-value ≤0.05 was applied to the significance of the r-values. Subsets of genes of interest were subjected to pathway enrichment using MetaCore (Clarivate Analytics). Simulation analysis (SIM) was performed to estimate any bias in correlation estimates caused by the number of levels used for different clinical scores. Results The plot (Figure 1) shows more genes with expression values that correlate significantly (q < 0.05) with RHI (4647), than UCEIS (1232), or MMS (869) (refer to legend). There are 498 genes that intersect all scores, representing predominantly the pathways/networks in Table 1. The RHI covers 86 % (1064/1232) of the genes that correlate with UCEIS. The genes unique to the UCEIS (168) do not significantly map to a specific pathway/network. Highest absolute r-values were RHI 0.56, GS 0.45, UCEIS 0.4 and MMS 0.3. The corresponding lowest q values expressed in −Log10 are 15, 9, 4, and 2.5. SIM shows only a minimal bias of <0.03 units (Pearson’s and Spearman’s r). Conclusion In our analysis, RHI tracked baseline gene expression values best, followed by another HP index (GS), followed by EN (UCEIS) and finally MMS. Judging by the orders-of-magnitude greater significance of correlation with gene expression values, the histology indices are particularly information-rich. Regulated gene expression, fundamental to a phenotypic appearance in HP, seems to best mirrored by the RHI, followed by GS. The genes that track with all indices predominantly modulate cell adhesion and leukocyte trafficking. The genes that are unique to the UCEIS, compared with the RHI, do not significantly belong to any recognisable pathway or network. Further evaluation of what current EN scores contribute relative to HP disease activity assessment in UC may be useful.

scholarly journals Narrow band imaging efficiency in evaluation of mucosal healing/relapse of ulcerative colitis

2018 ◽  
Vol 06 (05) ◽  
pp. E518-E523 ◽  
Author(s):  
Seiko Sasanuma ◽  
Kazuo Ohtsuka ◽  
Shin-ei Kudo ◽  
Noriyuki Ogata ◽  
Yasuharu Maeda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Blood Vessels ◽  
Narrow Band ◽  
Narrow Band Imaging ◽  
Mucosal Healing ◽  
Current Treatment ◽  
Mayo Score ◽  
Histological Activity ◽  
Histological Remission

Abstract Background and study aims Mucosal healing is a current treatment target in ulcerative colitis (UC), while histological remission is another target. The aim of this study was to evaluate the efficiency of magnified narrow band imaging (NBI) findings of mucosal healing and their relationship with histological activity and prognosis. Patients and methods Patients with UC who underwent total colonoscopy between January 2010 and December 2012 with left-sided or total-colitis type UC and achieved clinical remission with an endoscopic Mayo score of 0 or 1 were included. Each colon section was observed with white light and magnified NBI, with the colonoscopy being repeated at 1-year follow-up. We assessed the relationships of magnified NBI with histological disease activity and prognosis. Magnified NBI findings were divided into three categories; honeycomb-like blood vessels (BV-H), blood vessels shaped like bare branches (BV-BB), and blood vessels shaped like vines (BV-V). Results Fifty-two patients were included. The percentage of remitted mucosa with BV-BB was 37 %, while that of mucosa with scars with BV-H was 35 %. BV-H and BV-BB did not show pathological activity (12/292 and 8/299, respectively), while BV-V showed high pathological activity (27/33, 81 %). There was a correlation between magnified NBI findings and pathological findings (P < 0.01). The odds ratio for inflammation activity at 1-year follow-up was 14.2 for BV-BB (95 % CI, 3.3 – 60.9) Conclusion Magnified NBI findings showed a good relationship with histological activity. This suggests that we could estimate histological activity without biopsy, and also the possibility of predicting relapse over the following year.

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