Evaluation of Optimal Biopsy Location for Assessment of Histological Activity, Transcriptomic and Immunohistochemical Analyses in Patients With Active Crohn's Disease

Gregor Novak; Toer Stevens; Tanja Van Viegen; Peter Bossuyt; Borut Štabuc; Jenny Jeyarajah; Guangyong Zou; Ingrid C. Gaemers; Trevor D. McKee; Fred Fu; Lisa M. Shackelton; Reena Khanna; Gijs R. van den Brink; William J. Sandborn; Brian G. Feagan; Rish K. Pai; Vipul Jairath; Niels Vande Casteele; Geert D'Haens

Disclosures

Aliment Pharmacol Ther. 2019;49(11):1401-1409. 

In This Article

Results

Characteristics of the Patients

A total of 78 patients with Crohn's disease were screened; 51 met the eligibility criteria and were enrolled. Lack of at least a single ulcer >0.5 cm in diameter detected on ileocolonoscopy was the reason for all 27 screen failures. Baseline patient and disease characteristics are summarised in Table 1. The mean Simple Endoscopic Score for Crohn's disease of the study patients was 11 (SD = 7.5). Biopsies were procured from the ileum in 26, the colon in 18 and from both segments in seven patients.

Histopathological Scoring

Mean histological disease activity scores based on the GHAS, RHI and NHI and according to biopsy location and segment are shown in Table 2. Similar decreasing trends with distance from the ulcer edge (P < 0.05) were observed in histological disease activity scores in both the ileum and the colon, with all histological disease activity scores highest at the ulcer edge. Significant (P < 0.0001) differences were observed for all comparisons between the ulcer edge and locations 2 and 3 in both the ileum and the colon. Significant differences (P < 0.05) in histological disease activity scores were also observed between locations 2 and 3 in the ileum. Although there was a trend for decreased histological disease activity scores in location 3 relative to location 2 in the colon, these differences were not statistically significant. We also found no statistical differences in histological disease activity scores at any location between the colon and ileum (Table S3).

Transcriptomics

Log-transformed mRNA expression levels of IL-6, -8, -23 (p19 and p40 subunits), CD31 and S100A9 according to biopsy location and segment are shown in Table 3. Similar to histological disease activity scores, decreasing trends with distance from the ulcer edge were observed in proinflammatory mRNA expression in the colon and ileum (P < 0.05), with highest expression observed at the ulcer edge. Significant differences in mRNA expression were observed for all comparisons between the ulcer edge and locations 2 and 3 in both segments (P < 0.005). We also found no statistical differences in the expression of any of the genes of interest at any location between the colon and ileum (Table S3).

Immunohistochemistry

Log-transformed numbers of CD3+, CD68+ and myeloperoxidase-positive cells per mm2 according to biopsy location and segment are shown in Table 4. No significant differences in the number of CD3+ or CD68+ cells were observed according to biopsy location in the colon, whereas the number of myeloperoxidase-positive cells was highest at the ulcer edge and differed significantly compared to locations 2 and 3 (P < 0.0001). The number of CD3+ cells also did not differ according to biopsy location in the ileum, however significant differences were observed for the number of CD68+ cells at the ulcer edge and location 3 as well as between locations 2 and 3 in this segment (P < 0.05). Similar to the colon, the number of myeloperoxidase-positive cells in the ileum was highest at the ulcer edge and differed significantly compared to the number of cells observed at locations 2 and 3 (P < 0.0001), such that a decreasing trend was observed in the number of these cells in both the colon and ileum (P < 0.05). We also found no statistical differences in the number of marker-positive cells at any location between the colon and ileum (Table S3).

Safety

No serious adverse events, including bleeding or perforations, occurred during this study as a consequence of biopsy sampling. Eight Crohn's disease-related and incidental adverse events were reported in six patients (disease relapse [two patients], terminal ileum stenosis, fever, nausea, abdominal pain, small colonic polyps and a tubulovillous adenoma of the caecum), none of which were considered by the reporting investigator as related to the biopsy procedure.

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