Histologic Inflammation In Patients Research Articles

DOP35 Spatial transcriptomics reveals cellular niches associated with histological inflammation in postoperative Crohn’s Disease

Abstract Background Postoperative Crohn’s disease (CD) recurs in ~70% of patients ≤1 year following ileocolonic resection (ICR), as observed endoscopically. Current understanding of molecular determinants underlying histological intestinal inflammation in patients with postoperative CD recurrence is minimal. To address this issue, we used advanced spatial transcriptomic analyses on intestinal biopsy samples with matched histological and endoscopic assessments from neoterminal ileum, anastomosis, and colon of patients with CD who had undergone colonoscopy following ICR. Methods Formalin-fixed paraffin-embedded (FFPE) tissue biopsies from neoterminal ileum, anastomosis, and colon were prospectively collected from a 15-patient cross-sectional cohort with CD who underwent routine endoscopic assessment following ICR. Spatial transcriptomics was performed on samples using 10X Genomics Visium CytAssist Spatial Gene Expression for FFPE V2.0. Annotation of tissue regions of histologically active inflammation and classification of histologically inactive (Robarts Histopathology Index ≤3 with subscores of 0 for neutrophils in the lamina propria and epithelium) or active disease were performed by an expert gastrointestinal pathologist. R programming language was used for data analysis (Figure). Results Fourteen of the 43 (32.6%) FFPE biopsies had histological evidence of inflammation. Spatial transcriptomics clustering revealed a distinct transcriptional signature by the segregation of 4 clusters ("inflamed clusters") composed mostly (≥69%) of cells from samples defined by histologically active disease. Tissue regions identified as inflamed by expert pathologist annotation contributed to >46% of inflamed clusters’ composition and <15% of remaining clusters. Cell type decomposition and cellular niche analysis revealed immune (e.g., myeloid, T cells, and B cells) and epithelial cells in close proximity sharing a similar microenvironment in 3 inflamed clusters while the 4th cluster was composed of >90% epithelial cells. Differentially expressed genes from the inflamed clusters were similarly expressed across intestinal segments including inflamed anastomotic biopsies and were enriched for signalling pathways involving immune cells recruitment/activation, inflammatory signalling, extracellular matrix organisation, and oxidative stress response. Conclusion This is the first study to explore spatial transcriptomic signatures associated with histological inflammation in patients with postoperative CD recurrence. Our analysis revealed a spatial signature of cellular niches and signalling pathways arising upon histological inflammation, providing insight into therapeutic targets and biomarkers across anatomic locations and the anastomosis.

P436 The AI based Red Density score is correlated with the established and new histological indices for Ulcerative Colitis in an independent cohort

Abstract Background Red Density (RD) is an automated endoscopic tool that is developed for the objective evaluation of disease activity in ulcerative colitis (UC). The initial development integrated histological disease activity based on Robarts histological index (RHI) in the machine learning algorithm. New histological scores for UC have been developed since. The aim of this study was to establish the correlation between RD and the Nancy histological index (NHI) and PICaSSO Histologic Remission Index (PHRI). Methods Patients included in 4 centers in the ongoing PROCEED-UC study (NCT04408703) had assessment with RD in the rectum and sigmoid at baseline, w52 or early termination visit. Biopsies were taken according to protocol. Biopsies were scored for the Geboes score (GBS), RHI, NHI, PHRI in a blinded way after initial scoring convention training. Correlation was tested on patient level between mean RD per segment and the different histological indices based on Spearman correlation. Results In total 96 patients from 4 centers were included representing 2634 RD images from 400 colonic segments with biopsies and corresponding RD score. Mean (± SEM) rectal RD score was 32.7 (± 4.54), 33.69 (± 5.25) and 64.86 (± 31.71) at baseline, w52 and ET respectively. Mean sigmoidal RD score was 38.13 (± 3.68), 42.82 (± 11.80) and 77.33 (± 24.65) at baseline, w52 and ET respectively. Analysis based on the segment with the highest mean RD score per patient showed significant correlation with NHI (r=0.60, p<0.0001), PHRI (r=0.62, p<0.0001). In the rectum the RD score at all time points correlated significant with NHI (r =0,53, p<0.0001) and PHRI (r=0.63, p<0.0001). Similar correlation was seen in the sigmoid for NHI (r=0.51, p<0.0001) and PHRI (r=0.22, p0.0108). A RD score of <57.5 (Likelihood Ratio (LR) 4.176; AUC 0.7820 (95CI 0.7047 - 0.8593), p<0.0001) was associated with histological remission based on NHI (<2) and a RD score of < 64.5 (LR 9.821; AUC 0.8133 (95%CI 0.7053 - 0.9212), p<0.0001) with histological remission based on PHRI (=0). The current dataset demonstrated to be stable in line with the previously established RD cut-off with GBS and RHI. 1 Conclusion In an independent cohort of patients with UC the correlation with the established and new histological indices for UC is confirmed. This underlines the value of RD as an objective endoscopic tool for the assessment of histological and endoscopic disease activity in UC. Ref 1: Bossuyt P, Nakase H, Vermeire S, De G, Eelbode T, Ferrante M, et al. Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density. Gut. 2020;69:1778–86.

Serum Amyloid A as a Surrogate Marker for Mucosal and Histologic Inflammation in Patients with Crohn’s Disease

Abstract Background Inflammatory bowel disease (IBD) comprises a heterogeneous group of conditions affecting the gastrointestinal tract; Crohn’s disease (CD) and ulcerative colitis (UC) are the two main recognize dentities. Aim of the Work The aim of the study is to assess the correlation between Serum Amyloid A and mucosal inflammation in patients with Crohn’s disease Patients and Methods This study a prospective cross-sectional single centered study which was carried out on CD patients sought medical advice at Ain Shams outpatient clinics. Results Our results showed highly significant relation between SAA and most of symptoms namely fever, abdominal pain, blood in stool, tenesmus, urgency and number of bowel movements. However, there was no statistically significant relation to weight loss. It worth mention that the relation between SAA levels and history of smoking had borderline statistical significance, while the relation to gender was not statistically significant. Finally, our results showed the sentivity of the major studied markers to detect active CD namely SAA, CRP and Calprotectin was 87.9%, 78.8% and 81% respectively while their specificity was 87.9%, 97% and 60% respectively. SAA was the overall best performing biomarker for CD activity in the current results. Conclusion We concluded that: SAA levels are always significantly higher in patients with CD activity. SAA levels correlate well with all clinical and laboratory signs of CD activity. SAA has an overall accepted sensitivity and specificity which is compared to CRP and fecal calprotectin. Despite higher sensitivity and specificity, using SAA alone as a marker of activity may not achieve a satisfactory diagnostic performance. It's better to be used in combination with other biomarkers.

Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density

BackgroundThe objective evaluation of endoscopic disease activity is key in ulcerative colitis (UC). A composite of endoscopic and histological factors is the goal in UC treatment. We aimed to develop...

Magnification endoscopy with optical chromoendoscopy shows strong correlation with histologic inflammation in patients with inflammatory bowel disease.

Background and study aims Apart from mucosal healing as an established treatment goal in inflammatory bowel diseases (IBD), recent evidence suggests that histologic healing may become another key prognostic parameter in IBD patients. We aimed to evaluate whether magnification endoscopy with optical chromoendoscopy can accurately assess histologic inflammation in IBD patients. Patients and methods In this prospective study, 82 patients with IBD (30 UC, 52 CD) were included. In all patients, magnification endoscopy in conjunction with optical chromoendoscopy was performed and rated on a novel magnification endoscopy score by three independent endoscopists. Targeted biopsies of the imaged areas were obtained and results were compared against two histological scores in UC (Robarts Histopathology Index, RHI; Nancy Histology Index, NHI) and one score in CD (modified Riley index, mRI). Moreover, interobserver agreement was calculated. Results Magnification endoscopy showed strong correlation with histopathologic scoring in both UC (RHI: r = 0.83, NHI: r = 0.78, P < 0.05) and CD (mRI: r = 0.74, P < 0.05) with high accuracy, sensitivity, and specificity. Further, 25 % of patients with mucosal healing on standard endoscopy showed signs of microinflammation on magnification endoscopy with optical chromoendoscopy, while none of the patients with mucosal and vascular healing under magnification endoscopy with optical chromoendoscopy exhibited microscopic inflammation. Interobserver agreement for grading intestinal inflammation by magnification endoscopy with optical chromoendoscopy was substantial (κ > 0.7). Conclusion Magnification endoscopy in combination with optical chromoendoscopy shows strong correlation with histologic inflammation in patients with IBD. This approach has potential to reduce physical biopsies for monitoring of inflammatory activity in patients with IBD during colonoscopy.

DOP67 Magnification endoscopy with optical chromoendoscopy for in vivo assessment of histological inflammation in patients with inflammatory bowel disease

DOP67 Magnification endoscopy with optical chromoendoscopy for <i>in vivo</i> assessment of histological inflammation in patients with inflammatory bowel disease

The role of fecal calprotectin in investigating digestive disorders

Calprotectin is a protein found in human neutrophils, and it is released during active periods of inflammation. Fecal calprotectin is a sensitive stool test in the assessment of intestinal inflammation. Fecal calprotectin is used clinically to screen for organic intestinal pathology and as a noninvasive marker for disease activity in patients with inflammatory bowel disease (IBD). Studies have demonstrated a high sensitivity and specificity for detecting and diagnosing mucosal and histologic inflammation in patients with an elevated fecal calprotectin value. The most promising and clinically important use for fecal calprotectin is in the initial stages of diagnosis and ongoing assessment of disease activity in patients with IBD—Crohn’s disease (CD) and ulcerative colitis (UC). The use of objective markers of inflammation will continue to become more important and widespread in the future, as patients, providers, and payers increasingly desire noninvasive tests that can accurately detect and stratify mucosal and histologic inflammation so that treatment regimens can be optimized and complications such as a need for surgery or the development of a malignancy can be reduced.

The correlation analysis of LUTS and histological inflammation in patients with benign prostatic hyperplasia

Objective To investigate the relationship between LUTS and degree, type of prostate histological inflammation in patients with benign prostatic hyperplasia(BPH). Methods From October 2013 to June 2016, 150 patients with BPH(62-82 years old) were treated with selective TURP.After operation, the pathology examination was practised.According to the international prostatitis histological classification standard, the patients were divided into group A(without inflammation, 18 cases), group B(inflammation around gland, 45 cases), group C(gland inflammation, 33 cases) and group D(mixed inflammation group, 54 cases). There were no statistically significant differences among the 4 groups in age, course of disease, number of urinary retention and prostate volume(all P>0.05). The IPSS score before and 2 months after operation and the correlation between the IPSS and degree, type of histological inflammation were observed. Results In group A and C, the preoperative IPSS score and IPSS score at 2 months after surgery were (17.20±11.14)points, (8.45±5.14)points and (18.05±13.11)points, (9.85±5.25)points respectively, there were no statistically significant differences between the two groups(t= 0.485, 1.294, all P>0.05). There were no statistically significant differences between group B[(22.55±11.85)points, (13.24±6.46)points] and group D[(21.45±10.35)points, (12.36±6.04)points](t=0.824, 1.436, all P>0.05). The group B had statistically significant differences compared with group A and group C (t=2.689, 5.016, 3.642, 4.382, all P 0.05). Conclusion There is a close correlation between LUTS and inflammation around gland in patients with BPH, and the LUTS can aggravate with the increased inflammation around gland and do not relate with the gland inflammation. Key words: Prostatitis; Benign prostate hyperplasiu; Lower urinary tract symptoma

Serum Amyloid A as a Surrogate Marker for Mucosal and Histologic Inflammation in Patients with Crohn's Disease.

Serum amyloid A (SAA) is an acute-phase protein, but its role as a biomarker of disease activity in Crohn's disease is unclear. The aim of the study was to assess the correlation between SAA, inflammatory cytokines, and mucosal inflammation in patients with Crohn's disease and to investigate whether this marker might be useful in patients who do not have elevated C-reactive protein (CRP) levels despite having active disease. Cross-sectional study including patients with Crohn's disease who underwent colonoscopies for assessment of disease activity. Predictive variables were recorded at the time of the procedure and included demographics, phenotype of disease, medications, and collection of serum for cytokine analysis (SAA, CRP, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukins 8, 1β, and 6). The primary outcome was the presence of mucosal healing (MH) (absence of macroscopic and microscopic inflammation). Ninety-four patients were included. Sixty-eight (72.3%) had not achieved MH. SAA, CRP, intercellular adhesion molecule, and interleukin-6 levels were significantly lower in those patients with MH. SAA was the only test that performed well in the sensitivity/specificity analysis (receiver operating characteristic: 0.81, P = 0.046). A high SAA was able to identify 70% of the patients with a normal CRP but active inflammation. High circulating SAA levels can correlate with lack of MH and may be used as a surrogate marker for disease activity, even in those patients in whom CRP levels do not correlate with disease activity.

Serum Amyloid a as a Surrogate Marker for Mucosal and Histologic Inflammation in Patients With Inflammatory Bowel Disease

Introduction: While the level of the C-reactive protein (CRP) has been used as a biomarker in the assessment of patients with inflammatory bowel diseases (IBD), its correlation with mucosal inflammation is poor in some patients. Serum amyloid A (SAA) is also an acute phase protein, but its role as a biomarker of disease activity in IBD is unclear. The aim of the study was to assess the correlation between SAA and mucosal/histological inflammation in patients with IBD and to investigate if this marker might be useful in patients that do not present with elevated CRP despite having active disease. We also sought to assess if other inflammatory cytokines can be used as surrogate markers of IBD activity. Methods: Cross-sectional study including Crohn's disease (CD) and ulcerative colitis (UC) patients that underwent colonoscopies for assessment of disease activity. Predictive variables included demographics, phenotype of disease, IBD medications and laboratories (SAA, CRP, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukins 8, 1β and 6). The primary outcome was the presence of active endoscopic or microscopic inflammation. Quartile analysis and receiving operating curves (ROC) were performed to evaluate the association between CRP, SAA and other cytokines with mucosal inflammation. Results: 94 patients were included (43% were women, 92% had CD). 59 (62.8%) had active endoscopic disease and 71 (75.5%) had active microscopic inflammation. All patients were receiving a biologic, 23% were on prednisone and 39% were on combination therapy (biologic plus immunomodulator). Differences between the groups with and without active disease are shown in Table 1. SAA was the test that best predicted mucosal inflammation (Table 2). When stratifying by location of disease, SAA predicted inflammation in both isolated small bowel disease (ROC: 0.8) and colonic disease (ROC=0.78). High SAA levels (≥2.4 mg/mL) identified 83% (19/23) and 81% (13/16) of those patients with microscopic and macroscopic inflammation but normal CRP ( < 4mg/mL).Table 1: Differences between those patients with and without inflammationTable 2: Performance of the studied biomarkers for predicting macroscopic or microscopic disease activityConclusion: High circulating SAA levels can accurately predict endoscopic and microscopic inflammation and may be used as a surrogate marker for disease activity, especially on those patients in which CRP levels do not correlate with their disease activity. Further studies looking into how SAA can predict response to treatment and its role in long-term disease monitoring are warranted.Figure 1

Fecal Level of Calprotectin Identifies Histologic Inflammation in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission

Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136-696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30-172 μg/g) (P= .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin.

21 Developing a Confocal Microendoscopy- Based Classification System of Histologic Inflammation in Patients With Ulcerative Colitis

21 Developing a Confocal Microendoscopy- Based Classification System of Histologic Inflammation in Patients With Ulcerative Colitis

Correlations between complexed, free and total PSA levels with prostatic volume and histologic inflammation in patients with benign prostatic hyperplasia

Correlations between complexed, free and total PSA levels with prostatic volume and histologic inflammation in patients with benign prostatic hyperplasia