Rutgeerts Score Research Articles

Serum exosomal microRNA-144-3p: a promising biomarker for monitoring Crohn's disease.

BackgroundCrohn’s disease (CD) has a tendency for recurrence and requires adequate monitoring and personalized treatment. Since endoscopy is considerably invasive, serum biomarkers are required as alternatives for CD monitoring. Toward this, exosomal microRNAs (miRNAs) may serve as promising candidates. In this study, we aimed to assess the role of serum exosomal microRNA-144-3p (miR-144-3p) as a biomarker for CD monitoring.MethodsWe prospectively recruited 154 patients without a history of surgery (Cohort 1) and 75 patients who were to undergo intestinal resection (Cohort 2). Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination. The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction (PCR). Correlations between relative exosomal miR-144-3p levels, disease activity, and disease behavior were analysed. The area under the receiver-operating characteristic curve (AUC) was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and post-operative recurrence.ResultsA 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls (P < 0.001). The exosomal miR-144-3p levels were positively correlated with the simple endoscopic score of CD (ρ = 0.547, P < 0.001) as well as the Rutgeerts score (ρ = 0.478, P < 0.001). Elevated exosomal miR-144-3p levels were correlated with the penetrating disease with high specificity (100% [95% confidence interval, 95.1%–100%]). The accuracy of exosomal miR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein (CRP) (AUC, 0.775 vs 0.639; P < 0.001).ConclusionsSerum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD. It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.

A Patient Self-Made Point-of-Care Fecal Test Improves Diagnostic Accuracy Compared with Fecal Calprotectin Alone in Inflammatory Bowel Disease Patients.

Background: Monitoring inflammatory bowel disease patients may be challenging. Fecal calprotectin is one of the most performed tests. Other fecal biomarkers are less used in clinical practice. Rapid fecal tests that could be performed by patients may be a useful strategy to closely monitor disease activity. Methods: We performed a prospective observational study including consecutive inflammatory bowel disease patients referred for colonoscopy in a single center. Certest FOB + Transferrin + Calprotectin + Lactoferrin® (Certest Biotec S.L, Zaragoza, Spain), a one-step point-of-care test which simultaneously detects these four biomarkers was performed. Endoscopic inflammatory activity was defined using the Mayo score (≥1) in ulcerative colitis, SES-CD (>3) and Rutgeerts scores (≥1) for Crohn’s disease. Results: Out of a total of 106 patients (56.5% female, mean age 51 years), 54 (50.9%) were diagnosed with ulcerative colitis and 52 (49.1%) with Crohn’s disease. Endoscopic activity was detected in 42 patients (39.0%). Fecal calprotectin provided the best sensitivity (97.6%), with limited specificity (34.4%). Compared to calprotectin, the other 3 fecal biomarkers showed better specificity (87.5–92.1%) and lower sensitivity (45.2–59.5%). Patients with a negative result in all biomarkers (19/106—17.9%) had 100% (CI 95% 97.4–100) negative predictive value, while patients with the 4 biomarkers positive (13/106—12.3%) had 100% (CI 95% 96.1–100) positive predictive value of endoscopic inflammatory activity. AUROC of this 4 biomarker point-of-care test was 0.845 (95% CI 0.771–0.920), significantly higher than the AUROCs of any of the 4 biomarkers. Conclusions: This test may be a useful strategy to monitor inflammatory activity in clinical practice by excluding or prioritizing patients in need of a colonoscopy.

Recommendations for Standardizing Clinical Trial Design and Endoscopic Assessment in Postoperative Crohn's Disease.

The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn's disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

A Role for CXCR3 Ligands as Biomarkers of Post-Operative Crohn's Disease Recurrence.

Crohn's disease [CD] recurrence following ileocolic resection [ICR] is common. We sought to identify blood-based biomarkers associated with CD recurrence. CD patients undergoing ICR were recruited across six centres. Serum samples were obtained at post-operative colonoscopy. A multiplex immunoassay was used to analyse 92 inflammation-related proteins [Olink Proteomics]. Bayesian analysis was used to identify proteins associated with increasing Rutgeerts score. Identified proteins were used in receiver operating characteristic [ROC] analysis to examine the ability to identify CD recurrence [Rutgeerts score ≥i2]. Existing single cell data were interrogated to further elucidate the role of the identified proteins. Data from 276 colonoscopies in 213 patients were available. Median time from surgery to first and second colonoscopy was 7 (interquartile range [IQR] 6-9) and 19 [IQR 16-23] months, respectively. Disease recurrence was evident at 60 [30%] first and 36 [49%] second colonoscopies. Of 14 proteins significantly associated with Rutgeerts score, the strongest signal was seen for CXCL9 and MMP1. Among patients on anti-tumour necrosis factor drugs, CXCL9 and CXCL11 were most strongly associated with Rutgeerts score. Both are CXCR3 ligands. Incorporation of identified proteins into ROC analysis improved the ability to identify disease recurrence as compared to C-reactive protein alone: area under the curve [AUC] 0.75 (95% confidence interval [CI]: 0.66-0.82] vs 0.64 [95% CI 0.56-0.72], p = 0.012. Single cell transcriptomic data provide evidence that innate immune cells are the primary source of the identified proteins. CXCR3 ligands are associated with CD recurrence following ICR. Incorporation of novel blood-based candidate biomarkers may aid in identification of CD recurrence.

S699 Isolated Anastomotic Lesions Do Not Increase Risk for Severe Endoscopic Disease Progression in Postoperative Crohn’s Disease

Introduction: The impact of isolated postoperative anastomotic lesions on future Crohn’s disease (CD) progression is controversial. This study aimed to evaluate the risk of severe disease progression in postoperative CD patients with isolated anastomotic disease. Methods: Retrospective cohort study of adult CD patients who underwent ileocolonic resection (ICR) between the years 2009-2020. Patients with bowel continuity restoration, a postoperative colonoscopy ≤ 18 months from surgery, and ≥ 1 subsequent colonoscopy were included. Disease activity was assessed utilizing retrospective application of modified Rutgeerts’ score (RS) by a centralized reader. Primary outcome was severe endoscopic progression, defined as i3 or i4 disease. Secondary outcome was surgical recurrence defines as repeat ICR. Results: 199 CD patients (median age 34 years, 47.7% stricturing, 33.2% ≥1 prior ICR) with index postoperative colonoscopy RS of i0-i2b were included. Study population RS distribution was 28.8% (n=69) i0, 13.3% (n=32) i1, 20.4% (n=49) i2a, 20.4% (n=49) i2b. Median time from ICR to index colonoscopy (260 days [195,377.5]; p=0.83) and time to follow up endoscopy (441 days [335,746.5]; p=0.65) did not differ by index RS. Overall, 26.1% of patients experienced severe endoscopic disease progression and was associated with index RS (p< 0.001) (Figure 1). During entire follow up, adjusting for index RS, tobacco use, ≥2 prior ICR, and initiation of biologics after index ileocolonoscopy, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR:5.53 95% CI [2.50-12.76]; p< 0.001) and i2a disease (aOR: 2.63 [1.12-6.4];p=0.03). Conversely, i2a disease did not confer increased risk compared to patients in endoscopic remission (2.11 [0.89-4.97]; p=0.087) (Table 1). On multivariable Cox proportional hazard model, adjusting for risk factors, i2b disease was associated with decrease time to severe endoscopic disease progression relative to i0 or i1 disease (aHR: 4.68 [2.42-9.02]; p< 0.001) and i2a (aHR: 3.02 [1.50-6.09]; p=0.002). i2a was not associated with decreased time to endoscopic progression relative to i0 or i1 (p=0.25) (Table 1). Surgical recurrence was not associated with index RS (p=0.86). Conclusion: Mild ileal postoperative recurrence, not isolated anastomotic lesions, is associated with increased risk for severe endoscopic disease progression. Prospective studies are needed to further elucidate impact of isolated anastomotic inflammation.Figure 1.: Anti-receptor binding domain (RBD) antibody levels among IBD patients in PREVENT-COVID study. Box and whisker plots show mean (X), median, interquartile range, overall range of anti-RBD antibody levels (ug/mL), and proportion of participants with detectable anti-RBD antibody stratified by A) age group, B) vaccination type, C) IBD medication use (all participants), and D) medication use among patients not taking corticosteroids. Abbreviations: RBD = receptor binding domain, TNFi = tumor necrosis factor inhibitor, Immune = immunomodulator, 6-MP = mercaptopurine, AZA = azathioprine, MTX = methotrexate, 5ASA = mesalamine, vedo = vedolizumab, uste = ustekinumab.Table 1.: Baseline Demographics and Characteristics and Treatment adverse events throughout 8 weeks.

S2417 Acute Exacerbation of Crohn's Disease After COVID-19 Pfizer Vaccine

Introduction: Vaccine-associated autoimmunity is a well-known phenomenon attributed to either the cross-reactivity between antigens or the effect of adjuvant. The reactogenicity of COVID-19 mRNA vaccine in individuals suffering from immune-mediated diseases has not been investigated. We would like to present a case of Crohn’s disease flare up after receiving COVID-19 Pfizer vaccine. Case description/methods: 33 years old male with history of Crohn's Disease (CD) complicated by fistula formation s/p Right hemicolectomy with ileocolic anastomosis in 2014 was admitted due to abdominal pain, diarrhea and rectal bleeding for 2 days. Patient reported he did not have any CD symptoms and was off maintenance medications therapy for 1.5 years. He had first dose of COVID Pfizer vaccine 2 days before his symptoms have started. Physical examination was significant for tenderness in RLQ, vitals were stable and patient afebrile. A laboratory work up was significant for elevated ESR (22), iron deficient anemia, B12 deficiency, hypophosphatemia and hypomagnesemia. Stool studies were negative for signs of infection Abdominal and Pelvic CT scan with contrast shown stable enlarged mesenteric lymph nodes and no signs of acute inflamatory process.Colonoscopy showed Rutgeerts score i1 and no evidence of of colonic CD involvement. Colonoscopy also revealed active inflammation, ulceration and adenomatous change at ileocolic anastomosis. Patient was consulted with Gastroenterology and treated with Prednisone 40 mg, IV Iron, B12 and electrolytes with rapid improvement of patient’s symptoms. Discussion: During the past decades, there has been growing awareness of possible adverse events associated with vaccinations. When coming to COVID-19 vaccine, it is further complicated by the nucleic acid formulation and the accelerated development process imposed by the emergency pandemic situation. Currently formulated mRNA vaccines coding for the SARS-CoV-2 full-length spike protein have shown the highest level of evidence according to the efficacy and safety profile in clinical trials. Although the results from phase I and II/III studies have not raised serious safety concerns, patients with underlying immune-mediated disease were not specifically studied. mRNA vaccines may give rise to a cascade of immunological events eventually leading to the aberrant activation of the innate and acquired immune system that can be potentially associated with exacerbation of conditions involving dysregulated immune responses such as Crohn’s disease.

Thiopurines are superior to mesalamine for preventing postoperative recurrence in patients with Crohn's disease and two or more risk factors.

To confirm the hypothesis that thiopurines are better than mesalamine for preventing postoperative recurrence of Crohn's disease (CD) in patients with more than two risk factors. In total 87 consecutive CD patients who underwent curative ileocolonic resection and ileocolic anastomosis were retrospectively recruited, including 43 prescribed with thiopurines and 44 with mesalamine after surgery. Four risk factors were predefined for subgroup analyses: smoking, penetrating disease, perianal disease and previous resection. End-points included clinical (Crohn's disease activity index >200) and endoscopic recurrence (Rutgeerts score ≥i2) within 52 weeks. There were no significant differences in clinical (37.2% vs 54.5%, P=0.105) and endoscopic recurrence (55.8% vs 75.0%, P=0.060) between the thiopurines and mesalamine groups by week 52. In the subgroup analysis of patients with two or more risk factors, clinical (35.7% vs 81.8%, P=0.042) and endoscopic recurrence (64.3% vs 100%, P= 0.046) were less frequent in the thiopurine group than the mesalamine group. With one additional risk factor, the risk of endoscopic recurrence in the thiopurines group increased by 2.201-fold (95% confidence interval [CI] 1.178-4.115), adjusted for treatment intervention. While the risk of clinical and endoscopic recurrence in patients treated with mesalamine increased by 3.383-fold and 5.884-fold (95% CI 1.260-9.081 and 1.598-21.662). Three patients treated with thiopurines withdrew for adverse events. Thiopurines may be superior to mesalamine for preventing postoperative recurrence of CD in patients with two or more risk factors. Caution is needed in light of the adverse events caused by thiopurines.

The Relationship Between Endoscopic and Clinical Recurrence in Postoperative Crohn's Disease: A Systematic Review and Meta-analysis.

We aimed to quantify the magnitude of the association between endoscopic recurrence and clinical recurrence [symptom relapse] in patients with postoperative Crohn's disease. Databases were searched to October 2, 2020, for randomised controlled trials [RCTs] and cohort studies of adult patients with Crohn's disease with ileocolonic resection and anastomosis. Summary effect estimates for the association between clinical recurrence and endoscopic recurrence were quantified by risk ratios [RR] and 95% confidence intervals [95% CI]. Mixed-effects meta-regression evaluated the role of confounders. Spearman correlation coefficients were calculated to assess the relationship between these outcomes as endpoints in RCTs. An exploratory mixed-effects meta-regression model with the logit of the rate of clinical recurrence as the outcome and the rate of endoscopic recurrence as a predictor was also evaluated. In all, 37 studies [N = 4053] were included. For eight RCTs with available data, the RR for clinical recurrence for patients who experienced endoscopic recurrence was 10.77 [95% CI 4.08 to 28.40; GRADE moderate certainty evidence]; the corresponding estimate from 11 cohort studies was 21.33 [95% CI 9.55 to 47.66; GRADE low certainty evidence]. A single cohort study showed a linear relationship between Rutgeerts score and clinical recurrence risk. There was a strong correlation between endoscopic recurrence and clinical recurrence treatment effect estimates as trial outcomes [weighted Spearman correlation coefficient 0.51]. The associations between endoscopic recurrence and subsequent clinical recurrence lend support to the choice of endoscopic recurrence to monitor postoperative disease activity and as a primary endpoint in clinical trials of postoperative Crohn's disease.

Predictive value of tissue calprotectin for disease recurrence after ileocecal resection in pediatric Crohn's disease

Detection of possible predictive factors of endoscopic recurrence after ileocecal resection in Crohn's disease could be very beneficial for the individual adjustment of postoperative therapy. The aim of this study was to verify, whether immunohistochemical detection of calprotectin in resection margins is useful in diagnostics of endoscopic recurrence. In this study we included pediatric patients with Crohn's disease who underwent ileocecal resection, regardless of pre-operative or post-operative therapy (n=48). We collected laboratory, clinical, surgical, endoscopic and histopathological data at the time of surgery and at 6 months after surgery. The immunohistochemical staining of calprotectin antigen was performed on all paraffin blocks from the resection margins. Out of 48 patients 52% had endoscopic recurrence in the anastomosis (defined by Rutgeerts score) within 6 months after surgery. The number of cells positive for calprotectin in the proximal resection margin was negatively associated with recurrence (P=0.008), as was the elevated level of total calprotectin (from both resection margins). There was no correlation of calprotectin in distal resection margin and endoscopic recurrence. Fecal calprotectin over 100 ug/g (P=0.0005) and high CRP (P<0.001) at 6 months after ileocecal resection and peritonitis (P=0.048) were associated with endoscopic recurrence. Approximately half of the patients developed endoscopic recurrence within 6 months after ileocecal resection. The predictive value of tissue calprotectin is questionable, as it is negatively associated with endoscopic recurrence. There are other potentially useful predictors, such as CRP and fecal calprotectin at 6 months after resection and the presence of peritonitis.

Role of Intestinal Ultrasound in the Evaluation of Postsurgical Recurrence in Crohn’s Disease: Correlation with Endoscopic Findings

Introduction: Endoscopy remains the exam of choice in the evaluation of activity in Crohn’s disease (CD) after surgery (ACD-AS). However, intestinal ultrasound (IUS) may represent a noninvasive alternative. The objective of this study is to determine the diagnostic accuracy of this modality compared to endoscopy. Material and Methods: This is a cross-sectional study, comprising a period of 14 months, carried out in patients with established CD and ileocecal resection due to the disease. IUS (HI-VISION Avius®, Tokyo, Japan) was performed with linear probe B-mode/Doppler prior to ileocolonoscopy. IUS and ileocolonoscopy were performed on the same day by 2 specialists in Gastroenterology dedicated to ultrasound and inflammatory bowel disease, in a double-blind mode. Collected demographic and clinical data (Harvey-Bradshaw Index [HBI]; remission ≤4), serological/fecal inflammatory parameters (leukocytes [4–10 × 10⁹ cells/L], C-reactive protein [≤0.5 mg/dL], and fecal calprotectin [<50 mg/kg]), endoscopy (Rutgeerts score: remission <i2), and ultrasound (intestinal wall thickening [≤3 mm] and digestive wall vascularization using the semiquantitative score of Limberg [absent = 0, sparse = 1, moderate = 2, and marked = 3]). Results: Thirty-nine patients (female: 64.1%, mean age: 43.5 ± 15.3 years) were included. The median post-surgery follow-up was 9 years (IQR 3–12). The Montreal classification was as follows: L1, 61.5% (n = 24); L3, 38.5% (n = 15); B1 and B2, 28.2% (n = 11); and B3, 43.6% (n = 17). Most patients were in clinical remission (87.2%; n = 34), with a mean HBI of 2.1 ± 2.2. Twenty-two patients (56.4%) had normal inflammatory markers. IUS (intestinal wall thickening >3 mm and/or Limberg score >1) was abnormal in 61.5% (n = 24) of the cases. Endoscopic remission (Rutgeerts score <i2) in 53.8% (n = 21) of the cases. Compared to endoscopy, IUS (area under the receiver operating characteristic curve [AUROC] = 0.75, p = 0.007) showed a diagnostic accuracy superior to that of inflammatory parameters (AUROC = 0.66, p = 0.083) and clinical parameters (AUROC = 0.64, p = 0.139). IUS showed a moderate concordance with endoscopy (κ = 0.5, p = 0.001), which was higher than that with inflammatory parameters (ĸ = 0.33, p = 0.041) or clinical parameters (ĸ = 0.29, p = 0.01). Conclusions: Ultrasound evaluation of the digestive wall is a noninvasive technique that shows a good diagnostic accuracy and a moderate concordance with endoscopy, being superior to clinical and serological/fecal inflammatory parameters.

Role of fecal calprotection in predicting endoscopic recurrence in postoperative Crohn’s disease

Background and aims Fecal calprotectin (fCP) has been shown to correlate with endoscopic disease activity in Crohn’s disease (CD). The aim of this study was to evaluate its role in predicting early endoscopic recurrence in postoperative CD. Methods Patients who underwent CD-related intestinal resection with ileocolonic anastomosis were prospectively followed up until ileocolonoscopy was performed around 12 months post-surgery. Endoscopic recurrence (ER) was defined as modified Rutgeerts score i2b or higher. Endoscopic still images were reviewed by 2 independent reviewers blinded to fCP results. Stool specimens were collected 6 months post-surgery and a multivariate logistic regression model was established to explore the predictive value of fCP for ER. Results 79 patients were included. FCP was significantly associated with endoscopic recurrence (p = .036). A cut-off value of fCP of 267 µg/g at 6 months post-surgery predicted ER with a sensitivity of 61.8% and a specificity of 72.7% (AUC 0.669). A prediction model subsuming age at diagnosis and fCP 6 months post-surgery were significantly associated with ER (fCP at 6 months [p = .007] and age at diagnosis [p = .004], multivariate analysis). Conclusions FCP 6 months after surgery and age at diagnosis predict early ER at 1 year postoperatively. However, the low sensitivity of fCP still suggests the necessity of endoscopy as a gold standard for the assessment of postoperative recurrence of CD. KEY SUMMARY What is already known? Fecal calprotectin (fCP) correlates with endoscopic disease activity. Endoscopic recurrence occurs in up to 70% of patients after intestinal resection within 1 year. What are the significant and/or new findings of this study? Fecal calprotectin 6 months post-surgery and age at diagnosis significantly predict endoscopic recurrence at 1 year. Due to low sensitivity fCP cannot replace the necessity of endoscopy for accurate assessment of postoperative recurrence.

Endoscopic Prediction of Crohn's Disease Postoperative Recurrence.

The presence and severity of endoscopic recurrence after Crohn's disease intestinal resection predicts subsequent disease course. The Rutgeerts postoperative endoscopic recurrence score is unvalidated but has proven prognostically useful in many clinical studies. This study aimed to investigate the association between specific early endoscopic findings and subsequent disease course. In the setting of a randomized controlled trial (the POCER study), 85 patients underwent colonoscopy at 6 and 18 months after intestinal resection. Patients received 3 months of metronidazole, and high-risk patients received a thiopurine (or adalimumab if they were thiopurine intolerant). For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped up to a thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. Central readers confirmed Rutgeerts, Simple Endoscopic Score for Crohn's Disease, Crohn's Disease Endoscopic Index of Severity scores, and 5 newly tested endoscopic parameters: anastomotic ulcer depth (superficial vs deep), number of ulcers (0, ≤2, >2), ulcer size (1-5 mm, ≥6 mm), circumferential extent of ulceration (<25%, ≥25%), and the presence or absence of stenosis. The POCER index, based on the 6-month postoperative findings, was then developed in relation to predicting the endoscopic outcome at 18 months. Of the 5 parameters, the combination of ulcer depth and circumference at the anastomosis at 6 months was associated with endoscopic recurrence at 18 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.50; P = 0.035) with an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.5-0.75). The combination of these 2 parameters formed the basis of the POCER index (range, 0-4 with 0 denoting no ulcers and 4 denoting deep ulceration with >25% circumferential involvement). The new index had a strong correlation with the Rutgeerts score measured at the same time points: Spearmans' r = .80 at 6 months and r = .77 at 18 months (P < 0.001 at both time points). A POCER index of ≥2 and a Rutgeerts score of ≥i2 both had a sensitivity of 0.41 for recurrence; however, the POCER index had a higher specificity (0.8 and 0.67, respectively). The POCER index at 6 months was associated with endoscopic recurrence at 18 months (OR, 1.5; 95% CI, 1.2-2.0; P = 0.002; area under the receiver operating characteristic curve of 0.70; 95% CI, 0.57-0.82), but the Rutgeerts score was not (OR, 1.2; 95% CI, 0.8-1.8; P = 0.402). The POCER postoperative index comprises 2 key endoscopic factors related to the anastomosis that are associated with subsequent disease progression. A higher score, comprising the adverse prognostic factors of deep or circumferentially extensive anastomotic ulceration, may help identify patients who require more intensive therapy.

A Magnetic Resonance Imaging Index to Predict Crohn’s Disease Postoperative Recurrence: The MONITOR Index

We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.

Wireless Capsule Endoscopy for Diagnosis and Management of Post-Operative Recurrence of Crohn's Disease.

Despite aggressive medical therapy, many patients with Crohn’s disease require surgical intervention over time. After surgical resection, disease recurrence is common. Ileo-colonoscopy and the Rutgeerts score are commonly used for diagnosis and monitoring of post-operative endoscopic recurrence. The latter is the precursor of clinical recurrence and therefore it impacts prognosis and patient management. However, due to the limited length of bowel assessed by ileo-colonoscopy, this procedure can miss out-of-reach, more proximal lesions in the small bowel. This limitation introduces an important uncertainty when evaluating post-operative relapse by ileo-colonoscopy. In addition, the Rutgeerts score ‘per se’ bears a number of ambiguities. Here we will discuss the pros and cons of ileo-colonoscopy and other imaging studies including wireless capsule endoscopy to diagnose and manage post-operative recurrence of Crohn’s disease. A number of studies provide evidence that wireless capsule endoscopy is a potentially more accurate as well as less invasive and less costly alternative to conventional techniques including ileo-colonoscopy.

Diagnosis of postoperative recurrence of Crohn disease with MR-enterography: Value of diffusion-weighted imaging

PurposeTo compare the diagnostic capabilities of MR enterography (MRE) using contrast-enhanced (CE) sequences with those of MRE using diffusion-weighted (DW) imaging for the diagnosis of postoperative recurrence at the neo-terminal ileum and/or anastomosis after ileocolonic resection in patients with Crohn disease (CD), and to clarify the role of additional DW imaging to CE-MRE in this context. Material and methodsForty patients who underwent ileal resection for CD, and both endoscopy and MRE within the first year after surgery were included. There were 21 men and 19 women, with a mean age of 38 years±12 (SD) years (range: 18–67 years). MRE examinations were blindly analyzed independently by one senior (R1) and one junior (R2) radiologist for the presence of small bowel postoperative recurrence at the anastomotic site. During a first reading session, T2-, steady-state- and DW-MRE were reviewed (DW-MRE or set 1). During a separate distant session, T2-, steady-state- and CE-MRE were reviewed (CE-MRE or set 2). Lastly, all sequences were analyzed altogether (set 3). Performances of each reader for the diagnosis of postoperative recurrence were evaluated using endoscopic findings as the standard of reference (Rutgeerts score≥i2b). ResultsFifteen patients out of 40 (37.5%) had endoscopic postoperative recurrence at the anastomotic site. Sensitivity for the diagnosis of postoperative recurrence was 73% (95% CI: 51–96%) for R1 and 67% (95% CI: 43–91%) for R2 using set 1, and 80% (95% CI: 60–100%) for both readers using set 2. There was no significant differences in sensitivity between reading set 1 and reading set 2, for either R1 or R2 (R1, P> 0.99; R2, P=0.48). Specificity was 96% (95% CI: 88–100%) for both readers using set 1 or using set 2. Reading set 3 yielded an area under the ROC curve (AUC) of 0.93 (95% CI: 0.84–1) versus 0.89 (95% CI: 0.75–1) with set 1 (P=0.18) and versus 0.89 (95% CI: 0.78–1) with set 2 (P=0.21). No significant differences in AUC were found between set 1 or 2 and set 3 (P=0.18), nor between set 1 and 2 (P=0.76). Accuracies were 88% (95% CI: 74–95%) and 85% (95% CI: 71–93%) for DW-MRE for R1 and R2, respectively; 90% (95% CI: 77–96%) for CE-MRE for both readers; and 93% (95% CI: 80–97%) and 88% (95% CI: 74–95%) for R1 and R2 with set 3, respectively. ConclusionDW-MRE has diagnostic capabilities similar to those of CE-MRE for the diagnosis of postoperative recurrence of CD at the anastomotic site.

P288 Vedolizumab May Be An Effective Option For The Management Of Postoperative Recurrence Of Crohn’s Disease

Abstract Background The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn’s disease (CD) following ileocolonic resection is currently unknown. We aimed to assess the effectiveness of VDZ in this setting. Methods All consecutive CD patients with an available baseline colonoscopy at 6-12 months from the ileocolonic resection and treated with VDZ for the postoperative recurrence after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ. In patients with Rutgeerts score i0 or i1 at baseline, endoscopic success was defined by maintenance of Rutgeerts score i0 or i1; in patients with Rutgeerts score ≥ i2 at baseline, it was defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up. Results Seventy patients were included (median follow-up: 23.5 months). All 9 patients without endoscopic recurrence at baseline (Rutgeerts score i0 or i1) and available post-treatment colonoscopy maintained a Rutgeerts score i0 or i1 (treatment success: 100%). In patients with endoscopic recurrence (Rutgeerts score ≥ i2 at baseline), a reduction of at least one point in the Rutgeerts score was obtained in 20 out of 42 patients (47.6%). By combining the two subgroups, the overall endoscopic success was achieved in 29 out of 51 patients (56.9%). Furthermore, 14 out of 42 patients (33.3%) with endoscopic recurrence at baseline achieved a Rutgeerts score i0 or i1 at the subsequent colonoscopy. Clinical failure was reported in 13/70 patients (18.6%) at one year, and in 23/70 patients (32.9%) at the end of follow-up. A new resection was required in 7/70 patients (10.0%). Conclusion VDZ may be a therapeutic option for the management of postoperative recurrence of CD. Further studies are needed to confirm these results.

P354 Early treatment versus active surveillance after ileocolic resection in Crohn’s disease: a retrospective cohort study

Abstract Background Patients with Crohn’s disease (CD) often require ileocolic resection (ICR) due to refractory disease or disease-related complications, such as intestinal strictures, enteric fistulae or intra-abdominal abscesses. Up to 70% of patients will develop new endoscopic lesions in the neoterminal ileum within the first year after surgery. We assessed if the timing of postoperative treatment can reduce postoperative recurrence (POR) rate. Methods We performed a retrospective, single-center observational cohort study in a tertiary hospital. All CD patients undergoing abdominal surgery from January 1st 2015 until June 30th 2019 were screened. Patients with CD who underwent ileocolic resection with ileocolic anastomosis were included. Depending on the postoperative management patients were divided in two groups: “wait and see” if medical treatment was not initiated before endoscopic evaluation 6 months after surgery (n=109), “treat” if medical treatment was initiated directly after surgery (n=49). Patients whose postoperative follow-up occurred in another center were excluded. Data were collected by review of the electronic medical charts and included patient demographics, disease characteristics (Montreal classification), medication, indication for surgery and POR assessment. POR was defined as clinical (PRO2 pain &amp;gt;1 or loose stool frequency &amp;gt;1.5), endoscopic (Rutgeerts score &amp;gt; i2a) or radiologic (disease activity on MR enterography necessitating treatment). Survival analysis was performed with Kaplan-Meier and Cox proportional hazards model. Results In total 158 patients met the inclusion criteria: 109 patients in the “wait and see” group and 49 in the “treat” group. The main baseline characteristics of the cohorts are summarized in figure 1. The main indication for surgery was stricturing disease in both groups (69.7% and 65.3%) followed by penetrating disease (42.2% and 24.5%) and refractory disease (6.4% and 20.4%). Postoperative management did not significantly influence the risk for POR (figure 2). The same was also observed in patients with known risk factors for POR (figure 3). Patients with a high body mass index (&amp;gt;25 kg/m²) had a significant greater risk for developing POR (HR 1.65, CI 1.09-2.5, p=0.019; figure 4). Conclusion There was no statistical significant difference in POR between immediate treatment after ICR and active surveillance with endoscopy 6 months after surgery. Prospective randomized trials with long follow-up are needed to further explore the use of adjuvant postoperative treatment to prevent POR.

P215 Blood-based prognostic biomarkers in Crohn’s patients treated with biologics: a new promising tool to predict endoscopic outcomes

Abstract Background There is a growing need for biomarkers of inflammation to monitor and predict therapeutic outcome in Crohn’s disease (CD) patients. We aimed to evaluate whether the level of circulating blood cells, expressed as ratios (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; ELR, eosinophil-to-lymphocyte ratio and ENLR, eosinophil*neutrophil-to-lymphocyte ratio), could be used as early prognostic biomarker of endoscopic response (ER) in patients starting biological therapy with infliximab, adalimumab, vedolizumab and ustekinumab. Association with steroid-free clinical remission at week 54 and endoscopic disease activity at baseline, as well as other variables related with ER were also evaluated as secondary outcomes. Methods Consecutive patients with CD who started biological therapy between June 2016 and July 2019 in two Italian tertiary centers were enrolled. We used multivariate analysis to evaluate whether NLR, PLR, ELR and ENLR at baseline and after 12 weeks of treatment could predict ER (SES-CD ≤ 2 or SES-CD ≤ 2 and Rutgeerts score i0-i1) after 54 weeks of treatment. Receiver operating characteristic (ROC) curves were generated to identify the area under the curve (AUC) and find the best cut-off values of NLR, PLR, ELR and ENLR for the prediction of ER. To enhance the diagnostic performance, these ratios were combined with baseline Harvey Bradshaw Index (HBI) in a prognostic model. Results 107 patients were included. Patients who achieved ER had significantly lower baseline NLR (p = 0.025), ELR (p = 0.013) and ENLR (p = 0.021) compared with those without ER; similar results were confirmed after 12 weeks of treatment for ELR (p = 0.006) and ENLR (p = 0.026). AUC was 0.64 (p = 0.003), 0.67 (p = 0.006) and 0.65 (p = 0.014) for NLR, ELR and ENLR, respectively. The best cut-offs values were included in the HBI-based prognostic model: 81.8% of patients with HBI ≥ 5 and higher ratios did not achieve ER, while all patients with HBI &amp;lt; 5 and lower ratios reached ER. Interestingly, ENLR was found to be linearly associated with SES-CD at baseline (p = 0.035). Conclusion To the best of our knowledge, this is the first study assessing NLR, ELR and ENLR as predictive markers of therapeutic response in CD patients. Low levels of these ratios can predict endoscopic response and could be used in clinical practice for a better management of CD patients needing biological therapy. Further prospective studies are needed to confirm these results in larger cohorts.

Natural History and Risk Stratification of Recurrent Crohn's Disease After Ileocolonic Resection: A Multicenter Retrospective Cohort Study.

BackgroundPrediction of endoscopic postoperative recurrence (POR) and prophylactic treatment based on clinical risk profile have thus far been inconclusive. This study aimed to examine the association between clinical risk profile and the development of endoscopic POR in a Crohn’s disease population without postoperative treatment and to identify individual risk factors of endoscopic POR.MethodsMedical records of 142 patients with Crohn’s disease during follow-up after ileocecal or ileocolonic resection without prophylactic treatment at 3 referral centers were reviewed. Endoscopic POR was defined as a modified Rutgeerts score ≥i2b. Clinical risk profiles were distilled from current guidelines. Both uni- and multivariate logistic regression analysis were used to assess the relationship between risk profiles and endoscopic POR.ResultsEndoscopic POR was observed in 68 out of 142 (47.9%) patients. Active smoking postsurgery (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.24-7.34; P = 0.02), a Montreal classification of A3 (OR, 3.05; 95% CI, 1.07-8.69; P = 0.04), and previous bowel resections (OR, 2.58; 95% CI, 1.07-6.22; P = 0.03) were significantly associated with endoscopic POR. No significant association was observed between endoscopic POR and any guideline defined as a high-/low-risk profile. However, patients with a combination of any 3 or more European Crohns & Colitis Organisation– (OR, 4.87; 95% CI, 1.30-18.29; P = 0.02) or British Society of Gastroenterology–defined (OR 3.16; 95% CI, 1.05-9.49; P = 0.04) risk factors showed increased odds of developing endoscopic POR.ConclusionsOur results suggest that patients with a combination of any 3 or more European Crohns & Colitis Organisation– or British Society of Gastroenterology–defined risk factors would probably benefit from immediate prophylactic treatment.

Correlación entre la endoscopia y la ecografía intestinal para la evaluación de la recurrencia posquirúrgica de la enfermedad de Crohn

ObjectiveIntestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings. MethodsPatients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy. ResultsA total of 31 patients were included, of which 15 (48.4%) had no POR (RS<2b) and 16 (51.6%) had POR (RS≥2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75mm vs. 5.68mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%). ConclusionsIn our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy.