Prognostic value of histological activity in patients with ulcerative colitis in deep remission: A prospective multicenter study

Lobatón, Triana; Bessissow, Talat; Ruíz-Cerulla, Alexandra; Hertogh, Gert De; Bisschops, Raf; Guardiola, Jordi; Assche, Gert Van; Vermeire, Séverine; Ferrante, Marc

doi:10.1177/2050640617752207

Cited by 64 publications

(58 citation statements)

References 30 publications

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“…These differences between studies may reflect the influence of the microbiome and/or the animals’ age, as previously reported in experimental DSS colitis[ 27 , 28 ]. In addition, it has been reported that UC patients in clinical and endoscopic based remission presenting with active histological inflammation possess a higher risk for clinical relapse[ 29 , 30 ]. In this way, our study may provide an understanding of the pathological and clinical response of severe human UC, with higher chances of relapsing and chronic disease.…”

Section: Discussionmentioning

confidence: 99%

Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

Nunes

Kim

Sundby

et al. 2018

WJG

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AIMTo investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis.METHODSAcute colitis was induced in C57Bl/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon.RESULTSProgressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in pro-inflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80+, T helper CD4+ (Th), T cytotoxic CD8+ (Tcyt) and T regulatory CD25+ (Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut.CONCLUSIONThese results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS.

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Section: Discussionmentioning

confidence: 99%

Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

Nunes

Kim

Sundby

et al. 2018

WJG

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“…Recent data, however, indicates that MES 1 is not completely normal with regards to inflammatory histological state [6]. This increases the risk of relapse [7] and later complications. To achieve complete inflammatory remission, the aim should be MES 0.…”

Section: Introductionmentioning

confidence: 99%

Head to head comparison of two commercial fecal calprotectin kits as predictor of Mayo endoscopic sub-score and mucosal TNF expression in ulcerative colitis

Goll¹,

Heitmann²,

Moe³

et al. 2019

PLoS ONE

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BackgroundFecal calprotectin is widely used to monitor disease activity in patients with inflammatory bowel disease. Multiple commercial kits exist, however, since the analyses are not standardized, these kits cannot be used interchangeably. We aimed to perform a technical evaluation of two kits (Calpro from Calprolab, Norway and Calprest from Eurospital, Italy) and perform a tuning for detection of clinically relevant disease states in ulcerative colitis.Materials and methodsFor tuning against different clinical states a total of 116 patients with ulcerative colitis were recruited (67 of which were part of an earlier publication). For the technical evaluation an additional series of 80 random samples from the hospital lab were included. Technical evaluation was done by correlation and limits of agreement analysis; cut-off levels were explored by ROC analysis against clinically relevant actual states.ResultsThe technical evaluation revealed good correlation between assays, however a non-linear difference was found: At values below 200 mg/kg, no significant bias was found; in the interval 200–1000 mg/kg the Calprest assay measured on average 30% lower than Calpro; and at higher values Calprest measured 60% higher values than Calpro. Both assays predicted Mayo endoscopic score (MES) 0 (cutoff 28: sensitivity 0.38; specificity 0.82 for Calprest; cutoff 28: sensitivity 0.50; specificity 0.77 for Calpro), and MES 2–3 (cutoff 148: sensitivity 0.72; specificity 0.80 for Calprest; cutoff 208: sensitivity 0.64; specificity 0.80 for Calpro), but did not predict normalization of mucosal TNF transcript per se. A combination of calprotectin and MES predicted mucosal TNF transcript values reasonably well (Calpro: sensitivity 0.85, specificity 0.58; Calprest: sensitivity 0.85, specificity 0.61).ConclusionThe Calpro and Calprest assays correlated well, but subtle differences were found, underlining the need for kit-specific cut-off values. Both kits were most precise in predicting active inflammation (MES 2–3), but less so for prediction of mucosal healing (MES 0) and normalization of mucosal TNF gene expression.

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“…Data from rigorously designed, adequately powered studies are required to definitively address the role of colonic location with respect to biopsy procurement strategies in ulcerative colitis. Furthermore, while previous studies 4,11,12,20,21 have demonstrated that histological remission is a predictor of reduced risk of relapse in ulcerative colitis, longitudinal studies are needed to determine whether proximal, compared to distal, biopsies are relatively more predictive of outcome.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the optimum number of biopsies to assess histological inflammation in ulcerative colitis: a retrospective cohort study

Battat

Casteele

Pai

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundThe optimal ulcerative colitis biopsy protocol is unclear.AimTo evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitisMethodsBiopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4‐biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item‐level ratings from four biopsies, was compared to 1‐, 2‐ and 3‐biopsy estimates. Agreement was determined using bivariate errors‐in‐variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed.ResultsForty‐six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2‐biopsy (tolerance interval: −7.66, 4.79) and 3‐biopsy (tolerance interval: −4.86, 3.46) RHI scores demonstrated acceptable agreement with 4‐biopsy scores. One‐biopsy scores demonstrated unacceptable agreement (tolerance interval: −13.99, 7.78). Mean RHI scores using the 2‐, 3‐ and 4‐biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1‐biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2‐, 3‐ and 4‐biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1).ConclusionsA minimum of two — conservatively, three — biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice.

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Prognostic value of histological activity in patients with ulcerative colitis in deep remission: A prospective multicenter study

Abstract: In patients with UC in clinical and endoscopic remission, histological activity is an independent risk factor for clinical relapse. Further prospective studies need to clarify whether treatment optimization is justified in this context.

Cited by 64 publications

References 30 publications

Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

Head to head comparison of two commercial fecal calprotectin kits as predictor of Mayo endoscopic sub-score and mucosal TNF expression in ulcerative colitis

Evaluating the optimum number of biopsies to assess histological inflammation in ulcerative colitis: a retrospective cohort study

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