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(A) Endoscopy Mayo score 0; (B) histopathological examination of the same patient exhibiting mild crypt distortion only (Geboes grade, 0.1) (H&E, ×200). (C) Endoscopy Mayo score 1; (D) histopathological examination of the same patient showing significant acute inflammatory infiltrates in the lamina propria along with evidence of cryptitis (Geboes grade, 3.1) (H&E, ×400).
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Background/Aims
The therapeutic goal for treating ulcerative colitis (UC) patients has shifted to achieving mucosal healing over the past few years. However, at present, limited data is available on the correlation between endoscopic findings and histological remission in patients with endoscopic mucosal healing.
Methods
This was a prospective obs...
Context in source publication
Context 1
... to endoscopic biopsies from the rectosigmoid region. Histolog- ical remission was noted in 67.3% of patients (31/46), while 15 (32.7%) patients still had histologically active disease in the form of infiltration of the lamina propria by eosinophils and neutrophils (13/15, 86.6%), cryptitis (14/15, 93.3%), and crypt abscesses (8/15, 53.3%) (Fig. 2). The histological grades of these patients are summarized in Table 2. Of the 31 patients in histological remission, 16 (51.6%) had mild struc- tural changes while 14 (41.9%) had no structural changes ac- cording to the Geboes criteria, and 21 (67.7%) of the patients in histological remission had mild chronic inflammatory cells in the ...
Citations
... Compared to standard histology, it offers the advantage of dynamic analysis of the functional and morphological characteristics of the intestinal barrier [69]. The usefulness of this investigation lies in its capacity to assess epithelial permeability as well as the estimation of mucosal healing (MH) [70,71]. MH correlates with prolonged clinical remission, increased survival without surgical resection, and significantly lower hospitalization rates for patients with IBD [72][73][74]. ...
Inflammatory bowel diseases (IBD) represent a global phenomenon, with a continuously rising prevalence. The strategies concerning IBD management are progressing from clinical monitorization to a targeted approach, and current therapies strive to reduce microscopic mucosal inflammation and stimulate repair of the epithelial barrier function. Intestinal permeability has recently been receiving increased attention, as evidence suggests that it could be related to disease activity in IBD. However, most investigations do not successfully provide adequate information regarding the morphological integrity of the intestinal barrier. In this review, we discuss the advantages of confocal laser endomicroscopy (CLE), which allows in vivo visualization of histological abnormalities and targeted optical biopsies in the setting of IBD. Additionally, CLE has been used to assess vascular permeability and epithelial barrier function that could correlate with prolonged clinical remission, increased resection-free survival, and lower hospitalization rates. Moreover, the dynamic evaluation of the functional characteristics of the intestinal barrier presents an advantage over the endoscopic examination as it has the potential to select patients at risk of relapses. Along with mucosal healing, histological or transmural remission, the recovery of the intestinal barrier function emerges as a possible target that could be included in the future therapeutic strategies for IBD.
... Importantly, microscopic disease activity was associated with increased risk of negative outcomes and relapses. 13 Our study has several strengths. Firstly, to the best of our knowledge, this is the first study to analyze negative disease outcomes of UC during a long follow-up time of at least 1 year. ...
Background:
Clinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC.
Objective:
We aimed to evaluate the impact of disease clearance on long-term outcomes in UC patients.
Methods:
A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial-Mayo score ≤2), endoscopic (endoscopic-Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long-time follow-up (≥12 months), to compare the occurrence of negative outcomes.
Results:
A total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC-related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log-rank p < 0.0001) and surgery (log-rank p < 0.00095).
Conclusion:
In UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome.
... 42 Resolution of inflammation and not just symptoms is important, as it is associated with better long-term outcomes. 43,44 Performing repeated endoscopies to assess for endoscopic ± histological mucosal healing not only has limited patient acceptance but also carries the risks innate to the procedure. Alternative surrogate markers allowing noninvasive but accurate assessment of degree of endoscopic ± histological inflammation have therefore been extensively sought. ...
As the therapeutic targets in ulcerative colitis (UC) shift from control of symptoms to mucosal healing and prevention of disease complications like disability, colectomy, and cancer, the definition of remission has evolved. The current definition of clinical remission is variable and is determined by the clinical context in which it is being used. This results in skepticism and uncertainty about the true meaning of the term “clinical remission.” In this review, the authors reexamine the definition of clinical remission and propose a novel approach to define remission in UC.
... In our study, complete ER was defined as MES 0. Several studies reported that MES 0 (complete ER) has a lower relapse rate than MES 1 (partial ER) in UC patients [22,23,26,27]. Furthermore, recent studies reported that MES 0 was significantly associated with histological healing compared to MES 1 [28][29][30]. Recently, interest in histological healing as a treatment goal in patients with UC is increasing, and histological inflammation has been associated with a higher incidence of clinical relapse and development of colorectal neoplasia [27,30,31]. ...
Appendiceal orifice inflammation (AOI) is commonly considered a skip lesion in ulcerative colitis (UC). However, the clinical significance of AOI in UC patients remains controversial. This study aimed to evaluate the clinical feature and long-term outcomes of AOI by comparing UC patients with and without AOI. This study was conducted as a retrospective design of patients who were newly diagnosed or referred within 3 months after diagnosis at Seoul St. Mary’s Hospital from 1 January 2001 to 31 December 2020. All patients underwent index and follow-up colonoscopies. The long-term outcomes involved achieving complete endoscopic remission (ER), use of biologics, hospitalization, and proximal disease extension. Complete ER was defined as Mayo endoscopic subscore 0. In total, 318 UC patients were included, of which 140 had AOI. The baseline characteristics were not significantly different between AOI and non-AOI groups. The cumulative risk of complete ER was a significant difference between AOI and non-AOI groups (p = 0.041). The other cumulative risks of disease outcomes were not significantly different between AOI and non-AOI groups (use of biologics, p = 0.542; hospitalization, p = 0.795; proximal disease extension, p = 0.403). The multivariate Cox regression analysis also revealed that AOI was the significant factor of complete ER (hazard ratio, 0.656; 95% confidence interval, 0.462–0.932; p = 0.019) in UC patients. AOI shows a significant association with lower rate of complete ER in UC patients. Therefore, a meticulous treatment strategy may be recommended to achieve complete ER in UC patients with AOI.
... (also referred as histological healing) is an emerging treatment target and is an important outcome in UC clinical trials due to its association with favourable outcomes. [1][2][3][4][5][6][7][8][9][10] However, challenges remain on how to incorporate histology into clinical practice mainly due to: (1) the lack of a universal definition of HR to guide pathologists and (2) the lack of a sensitive, easily applicable histological score/index. Ideally, this index would be: (a) informative of and correlated with endoscopic assessment of disease activity, (b) representative of recovery/healing status of damaged mucosa and (c) predictive of disease outcomes. ...
Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity.
Methods
Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies.
Results
PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients’ risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy.
Conclusions
PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.
... Однако, несмотря на эндоскопические признаки заживления СОТК, при гистологическом исследовании, как правило, отмечается активность заболевания у 30-40% пациентов [8][9][10]. Согласно исследованиям, сохраняющаяся гистологическая активность воспалительного процесса у пациентов с ЯК увеличивает риск колоректальной неоплазии [11,12]. ...
... Концепция STRIDE определила эндоскопическое заживление СОТК как цель терапии ЯК, но некоторые исследователи считают, что заживление слизистой также включает отсутствие гистологических признаков воспаления, так как существует большое количество исследований, показывающих взаимосвязь гистологической ремиссии с благоприятными исходами заболевания [2,9,11,15,[24][25][26]. ...
Aim. To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy.
Materials and methods. We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS).
Results. We determined medium correlation between basic FC and MS before treatment (r=0.6605, p0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.82.1 mg/l, FC 409.344.85 g/g, medium GS 1.20.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.41.4 mg/l, FC 435.547.3 g/g, medium GS 1.350.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.41.1 mg/l, FC 290.617.5 g/g, medium GS 0.90.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease.
Conclusion. Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission
... However, histological activity may persist in patients with endoscopic mucosal healing and histological remission may be a better predictor than endoscopic remission of clinical outcome. 3 Much of the evidence is from studies of ulcerative colitis [UC]. ...
In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear.
In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardization of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardization and harmonization include biopsy procedures, biopsy-processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity.
In line with these needs, the European Crohn’s and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus.
There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.
... Результаты проспективного наблюдательного исследования V. Narang и соавт. [12] демонстрируют наибольшее значение гистологической ремиссии при ЯК по сравнению с эндоскопической ремиссией. В исследовании из 46 пациентов, достигших эндоскопической ремиссии в течение 6 мес, выполнено 4 биопсии из ректосигмоидных областей. ...
... При многофакторном анализе рецидивы ЯК зависели от индекса гистологической активности (p<0,001), но не от возраста, пола, длительности клинической ремиссии, степени активности воспалительного процесса или индекса эндоскопической активности Мейо. Было показано, что наличие лимфоцитарной или плазмоцитарной инфильтрации не имело значения для клинического течения ЯК (p=1,000), и это отличается от предшествующих публикаций [12]. Недавнее исследование M. Mosli и соавт. ...
Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.
... Significant proportions of patients who appear in endoscopic remission still have evidence of microscopic inflammation and suffer early relapse [28]. Whilst histological assessment of inflammation is considered gold standard and may help predict prognosis [29][30][31], it is reliant upon accurate biopsy sampling and incurs significant healthcare costs. RS Table 4 ...
Background
Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH.
Methods
Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification.
Results
A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm ⁻¹ and 1252cm ⁻¹ when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm ⁻¹ . The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively.
Conclusion
We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD.
... Nevertheless, a substantial number showed histologic inflammatory activity, indicating that histology can unveil inflammatory features in a population of patients in remission pre-selected on clinical and endoscopic findings. This is in line with previous publications[34,35].Compared to previous research, our results show lower concordance between raters. Jairath et al. had inter-rater ICC of 0.88, 0,86, 0,80 for GS, RHI and NI respectively[36] and Marchal-Bressnot et al. achieved a ICC value of 0.86 when developing the NI [20]. ...
Background
Histological evaluation of ulcerative colitis (UC) patients has been debated ever since the first description of the disease and its role in follow-up has never been fully established. Recent evidence suggests an added benefit in accuracy when evaluating if the patient is in remission. Unfortunately, there are several different histological indices, and it is difficult to compare outcomes where different scores are applied. Histopathological evaluation is prone to subjective biases, despite the use of indices. In addition, these indices are developed by expert IBD pathologist, but applied at large, by general pathologist. Therefore, we evaluated the three most applied histological indices for UC on samples from patients in remission to compare test qualities and estimate their usefulness to identify remission by both general and GI specialized pathologist.
Method
Mucosal biopsies from 41 UC patients in clinical and endoscopic remission were collected as part of a larger study on UC. Three pathologists blinded to the patients’ clinical status evaluated them using Geboes score (GS), Nancy Index (NI) and Robarts Histopathological Index (RHI). We calculated the agreement between the pathologists using Inter-class correlation (ICC) and visualized it with ICC-plots and Bland-Altman plots. Association between clinical factors and histological category were analysed by Fisher’s exact test.
Results
The ICC value for GS, RHI and NI were 0.85, 0.73 and 0.70 respectively. The limits of agreement were ±6.1, ±4.0 and ±1.4, for GS, RHI and NI, respectively. Mayo endoscopic subgrade and UC clinical score did not show association with any histological scores. Despite clinical and endoscopic remission 7–35% of the patients displayed histological inflammation on a level classified as active disease, depending on the index and cut-off.
Conclusion
A substantial amount of UC patients in clinical and endoscopic remission display inflammation on a histological level, but the ability to classify these patients accurately and consistently could be improved.
