Introduction

^​Intestinal ultrasound (IUS) is gaining increasing acceptance as a reliable tool for tight monitoring of ulcerative colitis (UC). Although several IUS scores have been proposed, none has been formally implemented into official recommendations of international scientific societies.

Aims & Methods

We aimed to compare an IUS score validated for Crohn’s disease (CD), the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS)¹, with other IUS scores specifically developed for UC, in terms of correlation with endoscopic activity.
Patients with UC ≥ 18 years old undergoing partial or full colonoscopy between April 2023 and January 2024 were prospectively included. Endoscopic evaluation of at least the sigmoid colon was mandatory for inclusion, and patients with proctitis (Montreal E1) were excluded. Endoscopic activity was scored with both the Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and defined by MES ≥ 1 and UCEIS ≥ 2. Moderate endoscopic activity was determined by a MES = 2 or an UCEIS = 5-6, while severe activity was defined by a MES = 3 or an UCEIS ≥ 7. IUS was performed within 4 weeks of endoscopy. The IBUS-SAS, the Milan Ultrasound Criteria (MUC)², the UC-IUS score³, the US Score from Parente et al.⁴, and the Hata index⁵ were included in the analysis. Applicability of the Civitelli index⁶, an IUS score developed for pediatric patients, was also evaluated. The Spearman’s rank coefficient [rho = ρ] was used to perform correlations, while receiver operating characteristic (ROC) curves were compared with the Hanley & McNeil method.

Results

Collectively, 104 patients were included in the study. The majority of patients (61.5%) had extensive colitis (Montreal E3), with half of them having an active disease at endoscopy (54.8% using MES and 48.1% using UCEIS). IUS examination was performed at a median time of 8 days (IQR 2-15) after endoscopy. All the investigated scores were significantly able to distinguish between the 3 grades of severity of colonic inflammation, using both MES and UCEIS as a reference, with the exception of the Parente’s US Score for the severe endoscopic activity assessed with UCEIS [0 (IQR 0-1) for UCEIS < 7 vs 1 (IQR 0-1) for UCEIS ≥ 7, p=0.09]. The IBUS-SAS showed a strong correlation with endoscopic activity, both with MES (ρ = 0.71, p < 0.01) and UCEIS (ρ = 0.73, p < 0.01) assessments. The Area Under the Curve (AUC) of IBUS-SAS to detect an endoscopic activity of at least moderate severity (MES ≥ 2 and UCEIS ≥ 5) was 0.85 and 0.90, respectively. The optimal cutoff to detect a MES ≥ 2 and UCEIS ≥ 5 was > 11 (sensitivity 75% and specificity 82%) and > 22 (sensitivity 92% and specificity 80%), respectively. Both cut-offs showed progressive increase from mild to severe activity, with IBUS-SAS maintaining a consistently high AUC at different thresholds. Consistent with IBUS-SAS results, all the investigated UC-developed IUS scores correlated with both the MES and the UCEIS (p < 0.01). AUC values and relative comparisons between the AUC are detailed in Table 1.

Table 1. Relative comparisons between the AUC of each score to detect a MES ≥ 2 (A, top-right) and an UCEIS ≥ 5 (B, bottom-left) are reported.
Grey rows and columns: AUC values (with 95%CI).
White cells: p-values obtained via the Hanley and McNeil method (significant p-values are shown in bold).

Conclusion

In this study we provide a successful validation of 6 IUS scores for UC. The IBUS-SAS has an optimal performance in predicting endoscopic activity also in patients with UC, despite having been developed initially for CD.

References

1. Novak KL, Nylund K, Maaser C, et al. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn's Disease. J Crohns Colitis 2021;15:609-616
2. Allocca M, Fiorino G, Bonovas S, et al. Accuracy of Humanitas Ultrasound Criteria in Assessing Disease Activity and Severity in Ulcerative Colitis: A Prospective Study. J Crohns Colitis 2018;12:1385-1391
3. Bots S, Nylund K, Löwenberg M, et al. Intestinal Ultrasound to Assess Disease Activity in Ulcerative Colitis: Development of a novel UC-Ultrasound Index. J Crohns Colitis 2021;15:1264-1271
4. Parente F, Molteni M, Marino B, et al. Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis?: a prospective study. Am J Gastroenterol 2010;105:1150-7
5. Kinoshita K, Katsurada T, Nishida M, et al. Usefulness of transabdominal ultrasonography for assessing ulcerative colitis: a prospective, multicenter study. J Gastroenterol 2019;54:521-529
6. Civitelli F, Di Nardo G, Oliva S, et al. Ultrasonography of the colon in pediatric ulcerative colitis: a prospective, blind, comparative study with colonoscopy. J Pediatr 2014;165:78-84.e2

Disclosure

GD reports speaker fees from Alfasigma, Johnson & Johnson, Novartis, Pfizer, Takeda, and has served in advisory board for Celltrion Healthcare and Pfizer. The other authors have no conflict of interests to declare.

Introduction

Between 50% and 70% of patients with Crohn’s disease (CD) will require an ileocecal resection. Surgery is not curative, and endoscopic recurrence is frequently observed at the anastomosis site and/or in the neo-terminal ileum.
The objective of this study was to analyse the mucosa-associated ileal microbiota at the time of surgery and during the colonoscopy performed 6 months later and to identify predictive factors of post-operative endoscopic recurrence.

Aims & Methods

Patients were recruited from 15 centres within the REMIND group. Since September 2010, the REMIND group has established a homogeneous, prospective, multicenter cohort (POP-REMIND, NCT03458195) of patients undergoing surgery for ileal and/or ileocolonic Crohn’s disease. Samples were collected from the surgical specimen and during endoscopy, centrally stored in a biobank, and analysed to identify factors associated with recurrence.
Inclusion criteria were: age ≥18 years, ileal or ileocecal CD requiring intestinal resection. Data were collected using an electronic case report form (eCRF). Post-operative treatment was prescribed according to a predefined algorithm. Clinical, therapeutic, biological, and endoscopic data (Rutgeerts classification) were collected 6 months after surgery.
The composition of the mucosa-associated ileal microbiota was analysed at the time of surgery in 140 patients (M0) and in 125 samples at the colonoscopy performed 6 months later (M6), using ultra-deep 16S and ITS2 sequencing (MiSeq, Illumina) to characterize bacterial and fungal microbiota.
We specifically selected patients who had not received antibiotics during the perioperative period to avoid biasing the analysed signal. Sequencing data were processed using the DADA2 pipeline. Alpha and beta diversity and microbiota composition were analysed. Bacterial taxa associated with clinical parameters were identified using MaAsLin2 (Multivariate Association with Linear Models), accounting for CD phenotype and treatments.

Results

We observed numerous differences in the ileal bacterial and fungal microbiota between M0 and M6, and between patients who experienced recurrence (>i2a) and those who were in remission at M6. At M6, the Rutgeerts score was the main factor associated with variability in microbiota composition. The abundance of certain species, notably a decrease of Faecalibacterium prausnitzii, or increase of Fusobacterium nucleatum and Akkermansia muciniphila, was differentially associated with a whole range of levels of the Rutgeerts score or with more specific scores characterizing the inflammation of the anastomosis or the ileum. In addition, machine learning approaches displayed better performances when considering the Rutgeerts score as a multilevel prediction instead of a binary classification, further confirming the need to consider its full range. Finally, we investigated the microbial community dynamics, which highlighted a denser network organisation after surgery and in the absence of recurrence, along with changes in keystone species.

Conclusion

The ileal microbiota associated with post-operative recurrence in CD follows a dynamic process characterized by several waves of alterations. The link between ileal microbiota and disease recurrence varies depending on whether the lesions are located at the anastomosis or ileum sites, supporting a different underlying pathogenesis for the inflammatory process at these two locations.