Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients with Crohn's Disease: A Pilot Study

Abstract Background Early changes in bowel behavior during anti-TNF induction therapy in Crohn’s disease (CD) are relatively unknown. We determined (a) onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound; and (b) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. Methods Consecutive ileal/ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline, and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. Results Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the non-response group (P=0.003, P=0.011). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P<0.001, P<0.001, P=0.003) in the response group. Baseline SWE values (21.3±8.7 vs. 15.3±4.7 kPa, P=0.022) and bowel wall thickness (8.5±2.3 vs. 6.9±1.5 mm, P=0.027) in the non-response group were significantly higher than in the response group. Conclusions This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

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P176 Expert consensus on acquisition and reporting of intestinal ultrasonography activity in Crohn’s disease. A prospective inter-rater agreement study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.305 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S225-S226

Author(s):

R T Wilkens ◽

K Nylund ◽

F Petersen ◽

F De Voogd ◽

C Maaser ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Wall Thickness ◽

Bowel Wall ◽

Expert Consensus ◽

Inflammatory Activity ◽

Rater Agreement ◽

Delphi Consensus ◽

Bowel Wall Thickness ◽

Independent Expert

Abstract Background Intestinal ultrasonography (IUS) is a promising cross-sectional imaging modality used to assess transmural disease and complications in Crohn’s disease (CD). Although recently positioned as a first-line modality for evaluation as per ECCO guidelines, standard measurements, reproducibility and nomenclature have not yet been clearly established. The aim of this study was to evaluate the inter-rater agreement for parameters identified as important by experts through Delphi consensus. Methods IUS parameters demonstrating inflammatory activity were systematically reviewed in the literature and presented to IUS experts. Individual parameters were selected by a blinded Delphi consensus panel to establish relative contribution to inflammatory activity in CD. Weighted grading of each parameter was further established by expert consensus. Image acquisition for optimal measurement was established by consensus. Two phases for evaluating inter-rater variability were undertaken. Phase 1: blind review by 8 readers of 20 de-identified CD cases. Cases with poor agreement were reviewed to clarify discrepancy and improve agreement. Phase 2: an additional 30 de-identified CD cases blindly were reviewed by 12 independent expert readers. Inter-rater agreement was evaluated for all 4 key parameters. Statistics were performed using Stata 16. Bowel wall thickness (BWT) was assessed using intraclass correlation coefficient (ICC) and the ordinal parameters using weighted Cohens Kappa. Results The Delphi process reduced 12 activity parameters to 4 key contributors including BWT, color Doppler signal (CDI), inflammatory fat and bowel wall echostratification (Figure 1). BWT was regarded as pathologic if the average of 4 measurements were > 3 mm for the small and large bowel, and grades of the additional parameters established (Table 1). Bowel wall thickness was comprised of 2 measurements in cross section and 2 in longitudinal orientation (Figure 2). Interobserver agreement was almost perfect for BWT: ICC=0.91 (95% CI 0.83 to 0.96) p = 0.001, while there was moderate agreement for CDI κ=0.60 (95% CI 0.48–0.72) p = 0.001. Agreement for inflammatory fat detection was also moderate with κ= 0.50 (95% CI 0.33–0.66) p = 0.001, while stratification was fair κ= 0.39 (95% CI 0.26–0.53) p = 0.001. Conclusion This expert consensus-based IUS activity score clearly establishes the reproducibility of this standardised approach to measure inflammatory activity in patients with CD. Using our method, BWT which is known as the most important parameter, is highly reproducible with CDI and inflammatory fat demonstrating moderate reproducibility. This score may provide the foundation for the future incorporation of IUS in research studies and clinical trials.

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Development and Validation of a Simple Ultrasound Activity Score for Crohn’s Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa112 ◽

2020 ◽

Author(s):

Fredrik Sævik ◽

Ragnar Eriksen ◽

Geir Egil Eide ◽

Odd Helge Gilja ◽

Kim Nylund

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Wall Thickness ◽

Bowel Wall ◽

Activity Index ◽

Reference Standard ◽

Colour Doppler ◽

Bowel Wall Thickness ◽

Ultrasound Score

Abstract Background and Aims To improve management of patients with Crohn’s disease, objective measurements of disease activity are needed. Ileocolonoscopy is the current reference standard but has limitations that restrict repeated use. Ultrasonography is potentially useful for activity monitoring, but no validated sonographic activity index is currently in widespread use. Thus, we aimed to construct and validate a simple ultrasound score for Crohn’s disease. Methods Forty patients were prospectively examined with ultrasound and endoscopy in the development phase. The Simple Endoscopic Score for Crohn’s Disease [SES-CD] was used as a reference standard. Seven ultrasound variables [bowel wall thickness, length, colour Doppler, stenosis, fistula, stratification and fatty wrapping] were initially included, and multiple linear regression was used to select the variables that should be included in the final score. Second, the ultrasound data from each patient were re-examined for interobserver assessment using weighted kappa and intraclass correlation. Finally, the activity index was validated in a new cohort of 124 patients. Results Length, fistula and stenosis were excluded. The combination of the remaining variables provided a multiple correlation coefficient of r = 0.78. Interobserver analysis revealed poor agreement for stratification and fatty wrapping and these were thus excluded. There was excellent interobserver agreement for the remaining score consisting of wall thickness and colour Doppler. In both patient cohorts, the ultrasound score correlated well with SES-CD [Development cohort: rho = 0.83, p < 0.001, Validation cohort: rho = 0.78, p < 0.001]. A receiver operating characteristic curve analysis revealed an area under the curve of 0.92 and 0.88 for detecting endoscopic activity and moderate endoscopic activity, respectively. Conclusions A simple ultrasound activity index for Crohn’s disease consisting of bowel wall thickness and colour Doppler was constructed and validated and correlated well with endoscopic disease activity. ClinicalTrials. gov ID: NCT03481751

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Correlation between the macroscopic severity of Crohn’s disease in resected intestine and bowel wall thickness evaluated by water-immersion ultrasonography

Scandinavian Journal of Gastroenterology ◽

10.1080/00365521.2019.1683224 ◽

2019 ◽

Vol 54 (11) ◽

pp. 1331-1338

Author(s):

Katsuki Yaguchi ◽

Tomohiko Sasaki ◽

Tsuyoshi Ogashiwa ◽

Masafumi Nishio ◽

Yu Hashimoto ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Wall Thickness ◽

Bowel Wall ◽

Water Immersion ◽

Bowel Wall Thickness ◽

Resected Intestine

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Bowel Wall Thickness at Abdominal Ultrasound and the One-Year-Risk of Surgery in Patients with Crohn's Disease

The American Journal of Gastroenterology ◽

10.1111/j.1572-0241.2004.40267.x ◽

2004 ◽

Vol 99 (10) ◽

pp. 1977-1983 ◽

Cited By ~ 39

Author(s):

Fabiana Castiglione ◽

Ilario de Sio ◽

Antonio Cozzolino ◽

Antonio Rispo ◽

Francesco Manguso ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Wall Thickness ◽

Bowel Wall ◽

Abdominal Ultrasound ◽

Bowel Wall Thickness ◽

One Year ◽

The One

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Serum bFGF and VEGF Correlate Respectively with Bowel Wall Thickness and Intramural Blood Flow in Crohn’s Disease

Inflammatory Bowel Diseases ◽

10.1097/00054725-200409000-00011 ◽

2004 ◽

Vol 10 (5) ◽

pp. 573-577 ◽

Cited By ~ 55

Author(s):

Antonio Di Sabatino ◽

Rachele Ciccocioppo ◽

Elia Armellini ◽

Raffaele Morera ◽

Laura Ricevuti ◽

...

Keyword(s):

Blood Flow ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Wall Thickness ◽

Bowel Wall ◽

Bowel Wall Thickness

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Semi-automatic bowel wall thickness measurements on MR enterography in patients with Crohn's disease

British Journal of Radiology ◽

10.1259/bjr.20160654 ◽

2017 ◽

Vol 90 (1074) ◽

pp. 20160654 ◽

Cited By ~ 5

Author(s):

Robiel E. Naziroglu ◽

Carl A.J. Puylaert ◽

Jeroen A.W. Tielbeek ◽

Jesica Makanyanga ◽

Alex Menys ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Wall Thickness ◽

Bowel Wall ◽

Mr Enterography ◽

Bowel Wall Thickness ◽

Thickness Measurements

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Bowel wall thickness as a differentiating feature between ulcerative colitis and Crohn's disease of the colon

Clinical Radiology ◽

10.1016/s0009-9260(79)80033-1 ◽

1979 ◽

Vol 30 (1) ◽

pp. 15-19 ◽

Cited By ~ 5

Author(s):

C.I. Bartram ◽

H. Herlinger

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Wall Thickness ◽

Bowel Wall ◽

Bowel Wall Thickness

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P384 Lower infliximab trough levels are associated with higher bowel wall thickness in Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.513 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S358-S358

Author(s):

C Frias Gomes ◽

B Morão ◽

C Neto Nascimento ◽

C Gouveia ◽

C Palmela ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Maintenance Therapy ◽

Wall Thickness ◽

Clinical Remission ◽

Bowel Wall ◽

Therapeutic Drug ◽

Bowel Wall Thickness ◽

Transmural Inflammation ◽

Trough Levels

Abstract Background Therapeutic drug monitoring (TDM) is currently used to optimise anti-TNFα therapy in Crohn’s disease, as higher infliximab trough levels (ITL) are associated with better rates of clinical remission and mucosal healing. Transmural healing is emerging as a potential target in Crohn′s disease, but whether there is any relation with ITL remains unclear. Here, we investigated the relation between ITL with bowel wall thickness (BWT) in patients with CD in maintenance therapy with IFX. Methods A retrospective cohort study of CD patients treated with IFX in mono or combination therapy. Patients were included if they had an available ITL during maintenance therapy and available entero-magnetic resonance or computerised tomography performed ±4 months. Transmural inflammation was defined as BWT ≥ 4 mm. Median BWT was measured in the most affected segment. An ROC curve was plotted to determine the best cut-off point of ITL to predict transmural inflammation. Mann–Whitney U-test, logistic regression and Spearman correlation were performed to assess the ITL relation with BWT. Results Twenty-nine patients were included (males 55.2%; mean age 39.6 ± 18 years; combo therapy 48.2%). According to the Montreal Classification, most patients were A2 (75.2%), with ileal (L1: 34.5%) or ileocolic disease (L3: 51.7%), and behaviour was: B1 41.4%, B2 24.1%, and B3 34.5%, with concomitant perianal disease in 37.9%. 82.2% were in clinical remission. The median IFX TL was 3.2 μg/ml (IQR 1.15–5.15) and median bowel wall thickness was 7 mm (IQR 4–9). 75.9% of patients had BWT > 4 mm. A BWT > 4 mm was associated with lower clinical remission rates (75% vs. 100%, p = 0.27) and higher C-reactive protein (0.31 vs. 0.14, p = 0.09), albeit not significantly. The area under the curve of ITL for bowel wall thickness was 0.70 (best cut-off value 1.8). Having ITL < 1.8 μg/ml was associated with higher median BWT (8.7 vs. 5.9 mm, p = 0.02) and was a predictive factor for transmural inflammation (OR 1.57, 95% CI [1.08–2.30], p = 0.02). BWT showed a fair correlation with ITL (r = −0.43, p = 0.02). Conclusion In our cohort of CD patients treated with infliximab (mono or combo therapy), lower infliximab trough levels were associated with higher bowel wall thickness, reflecting worse transmural inflammation. Proactive TDM could offer a possibility to improve BWT and reduce transmural inflammation.

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