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

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.

Ultrasonographic Evaluation of Bowel Wall Thickness and Intramural Blood Flow in Ulcerative Colitis

Background Ulcerative colitis, a type of inflammatory bowel disease that merely affects the mucosa and submucosa of colon in the form of inflammatory ulcers. Colonoscopy is the gold standard for its diagnosis. For optimal monitoring of disease activity in UC patients, colonoscopy should be performed on a regular basis. However, repeated colonoscopies represent a logistic and economic challenge, as well as significant burden for the patients. Objectives Our study aimed to provide an extensive overview of the main pathologic features of gut wall vessels and bowel wall thickness at US examination of UC. Patients and Methods This prospective case control study was done on 40 patients confirmed to have UC attending to Outpatient Clinics of Internal Medicine and Gastroenterology Department – Ain-Shams University from October 2018 to Augost 2019. They were divided into two groups: Relapse group: Include 20 patients with active UC disease. Remission group: Include 20 patients with inactive UC disease (in remission state). These two groups were matched with 20 healthy individuals, matched for age and gender and considered to be a control group. Disease activity was categorized according to the endoscopic Mayo score.Ultrasound and endoscopic findings were compared for each colon segment except for the rectum. Results The peak incidence of affected patients was 30–40 years of age. Female predominance compared to male with a ratio of 2.6:1. 20% of remission patients complaining from 1-2 bowel movement while 45% and 50% of relapsing patients suffer from 3-4 and 5 bowel movement respectively. 100%, 100%, 20% and 15% of relapsing patients suffer from bleeding per rectum, abdominal pain, tenesmus and urgency. Higher ESR and CRP and lower hemoglobin in relapsing compared to remission group. Furthermore, The last group has higher value of ESR and CRP and lower value of hemoglobin compared to control group. BWT was significantly thicker in relapse group (4.8±0.7 mm) than of remission (3.55±0.5 mm) compared to control group (1.6±0.5) (p value <0.001). BWT at a cut-offs > 4 mm discriminating between cases with relapse from those with remission and at a cut-offs >4 mm discriminating between mild endoscopic severity from moderate and severe UC. Furthermore, BWT at a cut-offs >4.6 mm discriminating between mild and moderate endoscopic severity from severe UC. Vascular signal number at a cut-offs >1 discriminating between cases with relapse from those with remission and at a cut-offs >2 discriminating between mild and moderate endoscopic severity of UC. Conclusion Abdominal ultrasound is a widely available non-invasive method for imaging of UC. It provides a high sensitivity, specificity and accuracy in diagnosis and monitoring of UC activity.

P283 Decrease in bowel wall thickness at intestinal ultrasound accurately detects early endoscopic remission and improvement in ulcerative colitis patients on tofacitinib: a longitudinal prospective cohort study

Background To assess disease activity in ulcerative colitis (UC) intestinal ultrasound (IUS) highly correlates with endoscopic outcomes. However, data on treatment response evaluated with IUS is limited. In this study we aim to evaluate bowel wall thickness (BWT) at follow-up to determine treatment effectiveness in moderate-severe UC patients treated with tofacitinib according to central read endoscopy and histology. Methods Patients with moderate-severe UC (endoscopic Mayo score (EMS)≥2) starting tofacitinib 10 mg bid were included. Disease activity was evaluated by recorded IUS cine-loops and video-taped endoscopies with biopsies from the sigmoid (SC) and descending colon (DC) at baseline and at 8 weeks. BWT and EMS were assessed per segment (SC and DC). Histology was scored for the SC with the Robarts Histology Index (RHI). BWT, EMS and RHI were centrally read and for IUS there was a second reader. Endoscopic remission (ERem) was defined as EMS=0, endoscopic improvement (EI) as EMS≤1 and endoscopic response (ERes) as a decrease of EMS≥1. For statistical analysis a Wilcoxon signed-rank and Spearman’s test were used. Area under the ROC was used to determine optimal cut-off values. Inter-observer agreement was analyzed by intra-class correlation coefficient (ICC). Results 29 patients were included and started tofacitinib. 10% reached complete ERem after 8 weeks, respectively. Per-segment analysis for EMS showed 22% and 53% reaching ER and 40% and 60% having EI in the SC and DC, respectively. BWT in SC and DC correlated highly with the EMS (rho=0.68, rho=0.75, both p<0.0001) and moderately with RHI (rho=0.49, p=0.002). Patients with EMS≥2 after 8 weeks had an increased BWT (SC: 4.32 ± 1.57 mm, DC: 4.38 ± 1.58 mm) when compared to ERem (SC: 2.10 ± 0.67 mm, DC: mean: 2.00 ± 1.18 mm, both p<0.0001) and EI (SC: 2.29 ± 0.76 mm, DC: 2.56 ± 1.38 mm, both p<0.0001) in the similar segment (Figure 1 and 2). BWT decreased after 8 weeks when there was ERes (SC: mean: -2.59 ± 1.44 mm, DC: -1.82 ± 1.01 mm, both p=0.007) and did not when there was no ERes (Figure 3). BWT cut-off values for ERem are reported in Figure 4. Furthermore, agreement for BWT in the SC and DC was excellent (ICC: 0.92 and ICC: 0.89), respectively. Conclusion BWT reduction showed early endoscopic remission, improvement and response after 8 weeks of tofacitinib treatment and correlated with histology in this central read cohort. Furthermore, accurate and reliable cut-off values for BWT in SC and DC were found for endoscopic remission and improvement. Therefore, IUS should be incorporated in the standard follow-up and close monitoring of UC patients.

P400 Bowel ultrasonography, a non invasive easy-to-use method to predict the need to step-up therapy in inflammatory bowel disease patients

Background Inflammatory bowel diseases (IBD) are chronic conditions that require multiple endoscopic and imaging assessments. Recent guidelines recommend bowel ultrasonography (BUS) as a complimentary imaging technique to assess transmural and extraintestinal lesions. The aim of the present study was to evaluate the accuracy of BUS in predicting the need to step-up therapy in IBD patients. Methods 117 IBD patients were included in the study (28 diagnosed with ulcerative colitis, 89 with Crohn’s disease). Following bowel ultrasound features bowel ultrasound features have been investigated: bowel wall thickness, loss of wall stratification, presence of bowel wall Doppler signal, the presence of hyperechoic spots inside the bowel wall, the irregularity of the external layer of the wall, the presence of creeping fat (mesenteric hypertrophy), the presence of visible lymph nodes. Patients were followed up for the next 6 months and data regarding their therapy was noted. Results During follow-up, therapeutic step-up, or biological treatment intensification (study outcome) were considered in 49.5% of cases in our study group. In a univariate analysis all the studied bowel ultrasound features but not the disease phenotype were significantly associated with the outcome. In the multivariate analysis only mean bowel wall thickness (<0.0001) and the presence of bowel wall Doppler signal (0.007) were independent predictors. Using the logistic regression prediction model, a score to evaluate the need of IBD treatment intensification could be calculated - Bowel Ultrasound Score (BU Score). The AUROC of the new BU score as a predictor for treatment intensification at 6 months in patients with IBD is 0.92, with a sensitivity of 84% and a specificity of 89%, indicating a good clinical utility. For the same outcome, AUROC for CRP was 0.81 whereas for fecal calprotectin was 0.85. Conclusion As the “treat to target concept” is the currently accepted novel treatment paradigm, incorporating BUS in IBD patients monitoring (BU score) provides an easy-to-use and readily available tool to stratify patients in need for therapeutic intensification.

DOP16 The ratio of submucosa thickness to the total bowel wall thickness can be a sonographic parameter to estimate endoscopic remission in Ulcerative Colitis

Background A less invasive examination that can estimate endoscopic remission is needed. Intestinal ultrasound (IUS) is a promising option. The bowel wall thickness (BWT) is a widely-accepted objective parameter in IUS to assess colonic inflammation, but BWT is influenced by intestinal peristalsis and the volume of luminal content. A feasible, objective index that is not affected by these factors could improve the diagnostic potential of IUS. The submucosa, which is observed as the third layer of the intestinal wall on IUS, becomes swollen and standing out in the active UC. Given BWT and submucosa thickness (SMT) can be influenced by the peristalsis and luminal content simultaneously, we hypothesized that the ratio of SMT to BWT can be an index for submucosal swelling regardless of those factors and this index can be a new parameter to estimate endoscopic remission. Methods Inclusion criteria were (1) both IUS and endoscopy (sigmoidoscopy or colonoscopy) for UC were performed in Kyorin University Hospital between April 2019 and December 2020 and (2) time-interval between IUS and endoscopy was within 2 weeks. BWT and SMT were measured based on IUS images for ascending (A/C), transverse (T/C), descending (D/C), and sigmoid colon (S/C), respectively. We defined the submucosa index (SMI) as a percentage of SMT to BWT (Figure 1). When SMT was too thin to be measured, we scored 0 for SMI. The loss of stratification (LOS) was defined as the condition where the submucosa cannot be identified even with BWT > 3 mm (Figure 2). The parts with LOS were considered as inflamed mucosa. Mayo endoscopic subscore (MES) was scored for each part of the colon based on the endoscopic images. MES of 0/1 was defined as the endoscopic remission. Informed consent was obtained in the opt-out method. This study was approved by the Institutional Review Board of Kyorin University School of Medicine (IRB No. 1668). Results In total 68 parts of the colon (A/C: 11, T/C: 12, D/C: 14, and S/C: 31) were analyzed. With ROC analysis with the Youden index, the cutoff value of BWT for endoscopic remission was 3.7 mm (AUC: 0.84). Among the parts without LOS, the cutoff value of SMI for endoscopic remission was 47.9 (AUC: 0.75). The positive predictive value for endoscopic remission of the diagnostic criteria (1) BWT ≤ 3.7 mm, (2) BWT ≤ 3.7 mm and no LOS, (3) SMI ≤ 48 (no LOS), and (4) BWT ≤ 3.7 mm, SMI ≤ 48 (no LOS) was 83.3%, 88.2%, 60.7%, and 93.3%, respectively. The negative predictive value was 88.0%, 88.2%, 90.0%, and 86.8%, respectively. Conclusion Given the feasibility and objectiveness of assessing bowel wall structure, our findings provide “proof of concept” that SMI can be an additional sonographic parameter for endoscopic remission.

P131 Serum Proteomics and Intestinal Ultrasound Differentiates Fibrostenotic and Inflammatory Crohn’s Disease

Background Fibrostenotic Crohn’s disease (CD) is a challenging phenotype often leading to surgical resection. Easily accessible and cost-effective diagnostic tools are needed to advance precision medicine to manage fibrostenotic CD patients. To date, there are no biomarkers that can discriminate stricturing CD from other phenotypes. Early studies suggest that protein biomarkers identified from serum proteomics may differentiate CD subtypes. Utilizing intestinal ultrasound (IUS), which readily detects strictures, the serum of patients with and without strictures was collected for proteomic characterization. Methods All consecutive CD patients attending outpatient appointments received IUS, and CT (computed tomography)/MR (magnetic resonance) within 6 months of study inclusion. Strictures were defined as a fixed segment of the ileum with increased bowel wall thickness (BWT) and luminal apposition with or without prestenotic dilation. Thirty two patients with ileal strictures were matched with CD patients without strictures (inflammatory behaviour). Serum of patients were collected for quantitative shotgun proteomics using liquid chromatography and tandem-mass spectrometry (LC-MS/MS). Results 64 patients in the stricture group had a significantly greater mean ileal bowel wall thickness (7.5 mm) compared to the inflammatory group (4.5mm, p = 0.02). A distinct and statistically significant protein signature was discovered between both patient populations. In the stricture group: plexin-A2, CD5 antigen-like protein, neogenin and dystonin were found, while in the non-strictured patients, matrix metalloproteinase 16, C-reactive protein, vinculin and apolipoprotein C-III were detected. Using Metascape and STRING-db, gene ontology and reactome pathway analyses, we identified enrichment of B cell differentiation and muscle contraction in the stricture patients, whereas in the non-stricture group, an enrichment for high-density lipoprotein remodeling, innate immune system and calcium ion transport were found. Conclusion We identified a unique protein signature that could robustly distinguish CD strictures from inflammatory phenotypes. This innovative diagnostic preliminary protein panel will be further expanded and validated in inflammatory and fibrostenotic CD populations, potentially allowing for future clinical decision optimization.

Good functional outcome following severe neutropenic enterocolitis and perforation in a 48-year-old woman undergoing chemotherapy for breast cancer

Neutropenic enterocolitis (NEC) is a life-threatening bowel condition, usually resulting from chemotherapy, with a mortality rate thought to be as high as 50%. Markers of poor prognosis include gastrointestinal perforation and bowel wall thickness radiologically detected to be greater than 10 mm. NEC is associated with severe neutropenia and predominantly affects the large bowel; however, we present a case of severe NEC with oesophageal perforation requiring transfer to a specialist upper gastrointestinal unit for corrective stenting. Despite initial bowel wall thickness of 20 mm in the ascending colon, two discrete episodes of bowel perforation and an inpatient stay totalling 89 days, the patient was discharged with full independence, a good quality of life and a plan for curative mastectomy plus axillary clearance.

Measurement of Bowel Wall Thickness by Transabdominal Ultrasonography Is Useful to Detect the Inflammation of Colon in Ulcerative Colitis Patients : A Retrospective Study

Background: Transabdominal ultrasonography (TUS) is a non-invasive method that can be performed repeatedly. Although the usefulness of TUS in ulcerative colitis (UC) has been reported, no well-established data exist yet. This study aimed to determine the usefulness of TUS, compared with colonoscopy (CS), in detecting the presence of mucosal inflammation in each segment of the colon among patients with UC. Methods: Eighty UC patients who underwent US within 14 days after CS were retrospectively registered. We divided the colon into five segments and measured the bowel wall thickness (BWT) using TUS. The results were then compared with the Mayo endoscopic subscore classification (MES) in order to determine their accuracy.Result: We evaluated a total of 268 lesions for each segment among 80 UC patients. The proportion of BWT decreased with an increase in the MES of each segment (p < 0.0001, Cochran-Armitage trend test). The sensitivity, specificity, and accuracy of positive BMT (BWT >2 mm) for detecting mucosal inflammation (MES >0) of each segment were 0.85-1.00, 0.78-0.93, and 0.87-0.98, respectively. Conclusion: This study concluded that TUS was a useful method for detecting the presence or absence of inflammation sites among UC patients due to its high accuracy when BMT >2 mm was considered as a positive finding. This non-invasive method may help control the disease activity of UC.

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

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 &lt; 0.001, Validation cohort: rho = 0.78, p &lt; 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