In recent years, we have seen a considerable increase in the number of patients with inflammatory bowel diseases of unknown etiology, including both Crohn's disease and ulcerative colitis. Inflammatory bowel diseases can cause intestinal lesions throughout the gastrointestinal tract, necessitating gastrointestinal endoscopy for examining all relevant aspects, especially lesion characteristics, for differential diagnosis and histological diagnosis, to select the appropriate treatment options, determine treatment effectiveness, etc. Specific guidelines are necessary to ensure that endoscopy can be performed in a safe and more tailored and efficient manner, especially since gastrointestinal endoscopy, including enteroscopy, is a common procedure worldwide, including in Japan. Within this context, the Japan Gastroenterological Endoscopy Society has formulated the "Guidelines for the Endoscopic Diagnosis and Treatment of Inflammatory Bowel Diseases" to provide detailed guidelines regarding esophagogastroduodenoscopy, enteroscopy, and colonoscopy procedures for definitive diagnosis, as well as determination of treatment effectiveness in clinical cases of inflammatory bowel diseases.

Fecal calprotectin (FC) is a reliable biomarker widely used for assessing disease activity and postoperative monitoring in patients with Crohn's disease (CD); however, its efficacy in patients with an ileostomy is poorly understood. Our study evaluated whether FC from the ileostomy output can be used to predict postoperative small bowel inflammation in patients with CD.

Data from patients with CD and an ileostomy who had undergone FC measurement between January 1, 2015, and December 30, 2022, were analyzed retrospectively. Patients were enrolled in the study if they had undergone FC tests with concurrent imaging and/or endoscopic studies, facilitating comparison between FC tests and imaging and/or endoscopic examinations. FC measured with the point-of care (POC) test was denoted as FC-POCT, and that measured using the enzyme-linked immunosorbent assay (ELISA) was denoted as FC-ELISA.

This study analyzed 101 patients and 224 FC test results. FC concentration differed significantly in patients with signs of small bowel inflammation on imaging and/or ileoscopy compared with those in remission (FC-POCT: median 191.0 µg/g; interquartile range [IQR], 94.6-499.0 µg/g vs. 29.9 µg/g; IQR, 29.9-50.0 µg/g; P < 0.001; FC-ELISA: median 252.5 µg/g; IQR, 118.5-911.0 µg/g vs. 16.8 µg/g, IQR, 8.2-33.0 µg/g; P < 0.001). The optimal cutoff value for FC-POCT and FC-ELISA to distinguish between small bowel inflammation and remission was 63.3 µg/g (area under the curve [AUC], 0.90; 95% confidence interval [CI], 0.88-0.97) and 40.1 µg/g (AUC, 0.89; 95% CI, 0.79-0.99), respectively. We also compared the diagnostic accuracy between the POC and ELISA testing methods and found no statistically significant difference (P = 0.692).

FC from the ileostomy output is a valuable biomarker with high sensitivity and specificity for monitoring small bowel inflammation in postoperative patients with CD and an ileostomy.

Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.

REPREVIO was a double-blind, randomised, placebo-controlled trial conducted at 13 academic or teaching hospitals in France, Italy, the Netherlands, and Spain. Eligible participants were adult patients aged 18 years or older with Crohn's disease who underwent ileocolonic resection and had one or more risk factors for recurrence. Patients were randomly assigned within 4 weeks of surgery (1:1 ratio) to receive intravenous vedolizumab (300 mg) or placebo at weeks 0, 8, 16, and 24. Randomisation was performed centrally with a computer-generated validated variable block model and patients were stratified according to disease behaviour (fibrostenotic vs inflammatory or perforating). Ileocolonoscopy was performed at week 26 and videorecorded. Endoscopic recurrence was centrally assessed with the modified Rutgeerts score, a categorial score ranging from i0 to i4. The primary endpoint was the distribution of modified Rutgeerts scores between treatment groups at week 26, analysed by non-parametric methods. The first-ranked secondary endpoint was the proportion of patients with severe endoscopic recurrence of Crohn's disease at week 26 (modified Rutgeerts score ≥i2b). Primary and safety analyses included all patients who underwent randomisation and received at least one dose of study drug. The trial is registered with the EU Clinical Trial Register (EudraCT; 2015-000555-24).

Between May 16, 2017, and April 8, 2022, 84 patients were randomly assigned to treatment, of whom four did not receive study treatment, leaving 43 patients in the vedolizumab group and 37 in the placebo group. At week 26, the probability of a lower modified Rutgeerts score with vedolizumab versus placebo was 77·8% (95% CI 66·4 to 86·3; p<0·0001). Severe endoscopic recurrence was observed in ten (23·3%) of 43 patients in the vedolizumab group versus 23 (62·2%) of 37 patients in the placebo group (difference -38·9% [95% CI -56·0 to -17·3]; p=0·0004). Serious adverse events occurred in three (7·0%) of 43 patients who received vedolizumab (bilateral tubo-ovarian abscesses, thrombosed haemorrhoids, and pancreatic adenocarcinoma) and in two (5·4%) of 37 patients who received placebo (intestinal perforation related to Crohn's disease and severe abdominal pain).

Vedolizumab treatment within 4 weeks of ileocolonic resection was more likely to prevent endoscopic Crohn's disease recurrence than placebo, making this an attractive option for postoperative management in patients with risk factors for recurrence. Larger studies with longer follow-up would be desirable.

Takeda Nederland.

Endoscopic assessment within 6 to 12 months of ileocolonic resection has been the mainstay of management of postoperative Crohn's disease. The original Rutgeerts score to grade endoscopic recurrence was designed for predicting prognosis after resection. However, it is increasingly recognized that the clinical course of disease varied based on anatomic location of lesion rather than only severity of endoscopic lesions. It is also important to recognize several anatomic landmarks around surgical anastomosis, given the vast technical modifications in surgical technique over the past few decades. It is important to understand the changing paradigm of assessing endoscopic recurrence as it considerably influences subsequent therapeutic management.

Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR).

In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed.

A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk.

In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

Anxiety over food choices and symptoms related to food consumption diminish quality of life (QoL) in inflammatory bowel disease (IBD) patients. However, the specific factors that impact QoL among IBD patients remain unclear. In this study, we analyzed the relationships of demographic and disease factors with food-related QoL (FRQoL) in a large, diverse US cohort of IBD patients.

In this cross-sectional analysis of 1108 IBD patients aged ≥18 years, we measured FRQoL with the 29-item Food-Related Quality of Life Questionnaire (FR-QoL-29) and disease activity with the Harvey-Bradshaw index in Crohn's disease (CD) patients or the Simple Clinical Colitis Activity Index in ulcerative colitis (UC) patients. Latinx immigrants completed a Spanish translation of the FR-QoL-29. A subset of patients had colonoscopy and inflammatory marker data available. We used univariate, multivariate, and subgroup analyses to examine the factors that influence FRQoL.

In our cohort, 55% of IBD patients self-identified as Latinx. Latinx and non-Latinx patients had similar FR-QoL-29 scores. Female patients had significantly lower FRQoL than male patients (P = .001). Increasing age and IBD duration correlated with higher FRQoL (P < .0001). In UC patients, higher Simple Clinical Colitis Activity Index scores (P < .0001), higher Mayo scores (P = .0009), and longer disease duration (P = .03) predicted significantly lower FRQoL. Disease activity and FRQoL were not significantly related in CD patients.

This is the largest study to date to examine FRQoL in American IBD patients, and the first to include Latinx patients. Disease-related factors had a greater impact on FRQoL than ethnicity. Clinical and endoscopic disease activity had a more detrimental impact on FRQoL in UC than in CD. Diet intervention studies are needed to alleviate symptoms and improve FRQoL in the IBD population.

Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries.

Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded.

In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications.

Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a costly condition in terms of morbidity and healthcare utilization, with an increasing prevalence now approaching 1% in the Western world. Endoscopic assessment of IBD remains the gold standard for diagnosis, evaluation of treatment response and determination of post-operative recurrence, but is expensive and invasive. Biomarkers can facilitate non-invasive disease assessment, with C-reactive protein and faecal calprotectin as the most widely available biomarkers in current clinical practice. This narrative review summarizes the evidence for their use in both UC and CD and offers practical guidance for healthcare providers taking into account the limitations of biomarker interpretation. We present evidence for the future use of novel biomarkers in IBD and discuss how biomarker discovery could deliver the goal of precision medicine in IBD.

Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort.

In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses.

A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002).

Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG.

Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity.

Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values.

Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

Inflammatory bowel disease (IBD) is a chronic disease characterised by repeated relapses and remissions and a high recurrence rate even after symptom resolution. The primary method for IBD diagnosis is endoscopy; however, this method is expensive, invasive, and cumbersome to use serially. Therefore, more convenient and non-invasive methods for IBD diagnosis are needed. In this study, we aimed to identify biological gas markers for the development of gut inflammation. Using dextran sulphate sodium (DSS)-induced colitis mouse models, five biological gases were analysed to identify predictive markers for the development of gut inflammation. Additionally, the correlation between the changes in gas composition, gut microbiota, and inflammatory markers was assessed. The hydrogen (H2) level was found to be negatively correlated with the level of lipocalin-2 (LCN2), a gut inflammation biomarker, and weight loss due to DSS-induced colitis. Furthermore, gut microbes belonging to the Rikenellaceae and Akkermansiaceae families were positively correlated with LCN2 levels and weight loss, whereas Tannerellaceae abundance was negatively correlated with LCN2 level and weight loss and positively correlated with H2 levels. This study provides new insights for IBD diagnosis; the H2 levels in biological gases are a potential biomarker for intestinal inflammation, and specific gut microbes are associated with H2 level changes.

Despite the introduction of potent biologic therapies, many patients with Crohn's disease [CD] still require an ileocolonic resection [ICR] during the course of their disease. Furthermore, the need of redo ICR has not decreased over the past few decades, highlighting the need for better strategies to prevent and treat postoperative recurrence [POR]. The first step to develop such a strategy would be to define and standardise the description of POR with adequate diagnostic instruments. In this article, we will describe the different methodologies used to report POR [endoscopic, histological, radiological, biochemical, clinical, and surgical], and review their potential benefits and limitations, as well as the optimal timing of evaluation.

This study aimed to investigate the cutoff value of leucine-rich alpha-2 glycoprotein (LRG) in predicting active intestinal ultrasonography (IUS) findings in patients with Crohn's disease (CD) in clinical remission. Data were retrospectively collected from patients with CD evaluated using LRG and undergoing IUS from September 2020 to August 2022. Patients with a Harvey-Bradshaw Index of ≤4 were included and those who underwent intestinal resection were excluded. Bowel wall thickness and stratification and blood flow signal using superb microvascular imaging (SMI) were used to assess ultrasonography findings. SMI signals were categorized into 4 grades following the Limberg score. Receiver operating characteristic curves were constructed and the area under the curve was calculated to determine the LRG cutoff values for predicting active IUS findings and were compared with those of C-reactive protein. This study included 213 patients. The LRG cutoff values to predict active bowel wall thickness, loss of bowel wall stratification, and SMI of ≥1, ≥2, and 3 were 14.6 μg/mL, 14.6 μg/mL, 14.6 μg/mL, 14.6 μg/mL, and 16.9 μg/mL, respectively, with significantly higher areas under the curve in SMI of ≥1 and 3 than in C-reactive protein. The best LRG cutoff value for predicting active IUS findings was 14.6 μg/mL in patients with CD in clinical remission, suggesting that LRG is better than C-reactive protein for detecting active IUS findings in CD.

We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD.

PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021.

Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD.

These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.

To retrospectively evaluate which key imaging features described by SAR-AGA on outpatient surveillance MRE correlate with progression to surgery in adults with CD.

52 CD patients imaged with outpatient MRE from 10/2015 to 12/2016 and with available clinical information were included. Two abdominal radiologists reviewed the MRE for the presence of active inflammation, intramural edema, restricted diffusion, stricture, probable stricture, ulceration, sacculation, simple fistula, complex fistula, sinus tract, inflammatory mass, abscess, perienteric inflammation, engorged vasa recta, fibrofatty proliferation, and perianal disease. Bowel wall thickness, length of bowel involvement, and degree of upstream dilation in strictures were quantified. Subsequent bowel resection, prior bowel surgery, and available laboratory values were recorded. The association between progression to surgery and imaging features was evaluated using a logistic regression model adjusting for demographics, prior bowel surgery, medication usage, and body mass index.

19.2% (10/52) of patients progressed to surgery. Restricted diffusion, greater degree of upstream dilation from stricture, complex fistula, perienteric inflammation, and fibrofatty proliferation were significantly more common in patients progressing to surgery (all p < 0.05). κ for these significant findings ranged 0.568-0.885. Patients progressing to surgery had longer length bowel involvement (p = 0.03). Platelet count, ESR, and fecal calprotectin were significantly higher, and serum albumin was significantly lower in patients progressing to surgery. Prior bowel surgery, sex, age, and all other parameters were similar.

Radiologists should carefully describe bowel dilation upstream from strictures, penetrating and perienteric findings on outpatient MRE in CD patients, as these findings may herald progression to surgery.

To compare terminal ileum (TI) mucosal iodine density obtained at dual-energy CT enterography (DECTE) with conventional CT interpretation and endoscopy in patients with Crohn's disease (CD).

Twenty-three CD patients (14 men; mean[SD] age:48.1[16.7] years) with endoscopy within 30 days of DECTE were retrospectively identified. An inflammatory bowel disease gastroenterologist reviewed endoscopic images. Two radiologists qualitatively assessed the presence of active TI inflammation. Mean iodine density normalized to the aorta (I%), mean absolute iodine density (I), and iodine density standard deviation (I_SD) from the distal 2 cm ileum (TI) mucosa obtained using semiautomatic prototype software were compared with endoscopic assessment using Mann Whitney tests. The optimal threshold I% and I were determined from receiver operating curves (ROC). Sensitivity and specificity of conventional interpretation and determined iodine thresholds were compared using McNemar's test. Inter-reader agreement was assessed using kappa. A p < 0.05 indicated statistical significance.

Twelve (52.1%) patients had endoscopic active inflammation. I% was 37.9[13.3]% for patients with and 21.7[7.5]% for patients without endoscopic active inflammation (p = 0.001). The optimal ROC threshold 24.6% had 100% sensitivity and 81.8% specificity (AUC = 0.909, 95% CI 0.777-1). I was 2.44[0.73]mg/mL for patients with and 1.77[1.00]mg/mL for patients without active endoscopic inflammation (p = 0.0455). The optimal ROC threshold 1.78 mg/mL I had 91.7% sensitivity and 63.6% specificity (AUC = 0.75, 95% CI 0.532-0.968). I_SD was similar for patients with and without endoscopic active inflammation (0.82[0.33]mg/mL and 0.77[0.28]mg/mL, respectively, p = 0.37). Conventional interpretation sensitivity and specificity (R1/R2) were 83.3%/91.7% and 72.7%/54.5%, respectively (all p > 0.05) with moderate inter-reader agreement (Κ = 0.542[95% CI 0.0202-0.088]).

Mean normalized iodine density is highly sensitive and specific for endoscopic active inflammation. DECTE could be considered as a surrogate to endoscopy in CD patients. Despite trends towards improved sensitivity and specificity compared with conventional interpretation, future larger studies are needed.

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.

Patients with postoperative Crohn's disease are difficult to manage because of their risk of experiencing a more severe course, multiple symptom confounders, and poor sensitivity of symptomatic remission to rule out intestinal inflammation. In this group, data are lacking on biologic therapeutic efficacy, and recommendations are lacking for those with multiple medication failures. Novel noninvasive testing can simultaneously exclude alternate causes of symptoms (serum C4, fecal fat, small intestinal bowel overgrowth breath testing) and assess intestinal inflammation (fecal calprotectin, endoscopic healing index). In addition, endoscopy-based disease activity assessment and management are required. Endoscopy should be performed within 6 months of surgery, and aggressive disease activity monitoring can be considered with colonoscopy every 1-2 years subsequently to ensure late recurrence is detected. Patients with multiple resections should be screened for short bowel syndrome. Predictive biomarkers are needed to guide medication selection in this high-risk population. Postoperative prophylactic biologic therapy is prudent for patients with preoperative biologic failure. However, there are no high-quality data to guide which agent should be selected. Selecting biologics with an alternative mechanism of action in those who had failed a biologic with adequate drug concentrations and selection of different agents in those with previous intolerance are reasonable. Significantly more study is required to assess the efficacy of therapies in this setting.

Crohn's disease recurs after intestinal resection. This study evaluated accuracy of a new blood test, the Endoscopic Healing Index [EHI], in monitoring for disease recurrence.

Patients enrolled in the prospective POCER study [NCT00989560] underwent a postoperative colonoscopic assessment at 6 [2/3 of patients] and 18 months [all patients] following bowel resection, using the Rutgeerts score [recurrence ≥i2]. Serum was assessed at multiple time points for markers of endoscopic healing using the EHI, and paired with the Rutgeerts endoscopic score as the reference standard.

A total of 131 patients provided 437 serum samples, which were paired with endoscopic assessments available in 94 patients [30 with recurrence] at 6 months and 107 patients [44 with recurrence] at 18 months. The median EHI at 6 months was significantly lower in patients in remission [Rutgeerts <i2] than those with recurrence; p = 0.033. The area under the receiver operating curve [AUROC] for EHI to detect recurrence at 6 months was comparable to that of faecal calprotectin [0.712 vs 0.779, p = 0.414]. EHI of <20 at 6 months had a negative predictive value of 75.7% (95% confidence interval [CI] 58.8-88.2), and sensitivity of 70% [95% CI 50.6-85.3] for detecting recurrence. Combining all time points, an EHI <20 had a negative predictive value of 70.3%. Changes in EHI significantly associated with changes in Rutgeerts scores over the 18 months.

The non-invasive multi-marker EHI has sufficient accuracy to be used to monitor for postoperative Crohn's disease recurrence. A monitoring strategy that combines EHI with ileocolonoscopy, with or without faecal calprotectin, should now be prospectively tested.

Many patients with Crohn's disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery.

This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups.

In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011).

Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease.

Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence.

One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86).

Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Endoscopic recurrence is common in postoperative patients with Crohn's disease (CD). Monitoring endoscopic recurrence is important for selecting an appropriate treatment to prevent the development of postoperative disease. The aim of this study was to develop and validate a diagnostic model to identify endoscopic recurrence.

This was a retrospective cohort study recruiting postoperative CD patients who underwent endoscopy at the First Affiliated Hospital, Sun Yat-sen University from January 2016 to June 2020. Endoscopic recurrence was defined as Rutgeerts score > i1. Thirty non-invasive biomarkers, including C-reactive protein, erythrocyte sedimentation rate, vitamin D, complete blood count, and biochemical blood indices, were used as candidate predictors to build a multivariate logistic regression diagnostic model. The predictive ability of the diagnostic models was assessed by receiving the area under the characteristic curve (AUC) and calibration plots, and internal validation was performed by the bootstrap method.

Two hundred and nineteen eligible patients were included in this study, and 135 (61.6%) patients had a postoperative endoscopic recurrence. The final diagnostic model included eight biomarkers with an AUC (95% confidence interval (CI)) of 0.796 (0.737-0.855) to identify endoscopic recurrence. The AUC, sensitivity, and specificity of this diagnostic model were 0.781 (0.780-0.782), 0.647 (0.643-0.651) and 0.811 (0.807-0.815), respectively, by internal validation. In addition, the diagnostic model exhibited good calibrability with calibration slope, calibration-in-the-large ('mean calibration') and Brier scores of 1.00, 0.00, and 0.175, respectively.

This non-invasive biomarker-based diagnostic model has an excellent ability to identify endoscopic recurrence in patients with CD. Application of the model to clinical practice to monitor postoperative patients may be helpful for patient management.

Short- and long-term treatment targets in inflammatory bowel diseases (IBDs) evolved during the last decade, shifting from symptom control to endoscopic healing and patient-centered parameters. The STRIDE-II consensus placed these targets on a timeline from initiating treatment and introduced additional targets, normalization of serum and fecal biomarkers, restoration of quality of life, prevention of disability, and, in children, restoration of growth. Transmural healing in Crohn's disease and histologic healing in ulcerative colitis currently serve as adjunct measures to gauge remission depth. However, whether early treatment according to a treat-to-target paradigm affects the natural course of IBD remains unclear, leading to the need for prospective disease-modification trials. The SPIRIT consensus defined the targets for these trials to assess the long-term impact of early treatment on quality of life, disability, disease complications, risk of neoplastic lesions, and mortality. As further data emerge about the risk-benefit balance of aiming toward deeper healing, the targets in treating IBDs may continue to shift.

The level of fecal calprotectin (FC) correlates with endoscopic evidence of inflammation in Crohn's disease (CD). A treat-to-target algorithm for patients with CD, that incorporates FC, outperforms a treatment strategy based on symptoms alone in the induction of mucosal healing at 12 months. We investigated whether normalization of FC within 12 months of diagnosis of CD is associated with a reduction in disease progression.

We performed a retrospective cohort study at a tertiary IBD centre in the United Kingdom. We identified all incident cases of CD diagnosed from 2005 through 2017. Patients with a FC measurement ≥250 μg/g at diagnosis who also had at least 1 follow-up FC measurement within the first 12 months of diagnosis and >12 months of follow up were included. The last FC measurement within 12 months of diagnosis was used to determine normalization (cut-off <250 μg/g). The primary endpoint was time to first disease progression (composite of progression in Montreal disease behavior B1 to B2/3, B2 to B3, or new perianal disease; CD-related surgery; or CD-related hospitalization). Cox proportional hazards regression analysis was used to determine independent factors associated with time to first disease progression.

A total of 375 patients out of 1389 incident cases were included, with a median follow up of 5.3 years (interquartile range, 3.1-7.4 years). Normalization of FC within 12 months of diagnosis was confirmed in 43.5% of patients. Patients with normalized levels of FC had a significantly lower risk of composite disease progression (hazard ratio [HR], 0.36; 95% CI, 0.24-0.53; P < .001). They also had a lower risk of reaching any of the separate progression endpoints (progression in Montreal behavior or new perianal disease HR, 0.22; 95% CI, 0.11-0.45; P < .001; hospitalization HR, 0.33; 95% CI, 0.21-0.53; P <.001; surgery HR, 0.39; 95% CI, 0.19-0.78; P = .008) CONCLUSIONS: Normalization of FC within 12 months of diagnosis is associated with a reduced risk of progression of CD.

Ileocolonoscopy with histology has been considered the gold standard for Crohn disease (CD) diagnosis and monitoring. Over the last years, magnetic resonance enterography (MRE) has become more and more popular, representing a valid non-invasive technique.

To propose a simplified MRE score, the pediatric CD magnetic resonance index (PCDMRI), based only on the most affected bowel segment, to grade active inflammation in children with CD.

Two radiologists retrospectively evaluated MRE images of children with histopathology-proven CD. The PCDMRI was based on six mural and perimural variables assessed for the most affected bowel segment (chosen by visual inspection of the key bowel wall imaging findings associated with active inflammation), and five extramural per-examination features. Correlation analysis was performed between both the PCDMRI and the MRE global score (based on all the affected segments) and the pediatric clinical disease activity index (PCDAI), the simple endoscopic score for CD (SES-CD), serum C-reactive protein (CRP) and fecal calprotectin (fC). Inter-reader reproducibility of the scoring system was estimated. Agreement on disease location between MRE and ileocolonoscopy was evaluated.

The study involved 42 children for a total of 80 MRE. PCDMRI and global score positively correlated with PCDAI, SES-CD, CRP and fC. Inter-reader reproducibility was 91%. Agreement on disease location was substantial.

The PCDMRI and the global score resulted equally correlated with the PCDAI, suggesting a high impact of the most affected segment on symptoms. The PDCMRI may be a useful non-invasive tool for a rapid and reproducible grading of the disease activity in children with ileocolonic CD.

Background Dual-energy CT enterography (DECTE) has been shown to be useful in characterizing Crohn disease activity compared with clinical markers of inflammation but, to the knowledge of the authors, comparison has not been made with histopathologic specimens. Purpose To compare mucosal iodine density obtained at DECTE from Crohn disease-affected bowel with histopathologic specimens from surgically resected ileocolectomy bowel segments or terminal ileum colonoscopic biopsies in the same patients. Materials and Methods This was a retrospective study. Bowel segments in adults with Crohn disease who underwent DECTE from January 2017 to April 2019 within 90 days of ileocolectomy or colonoscopy were retrospectively evaluated with prototype software allowing the semiautomatic determination of inner hyperdense bowel wall (mucosal) mean iodine density, normalized to the aorta. Mean normalized iodine density and clinical activity indexes (Crohn Disease Activity Index [CDAI] and Harvey-Bradshaw Index [HBI]) were compared with histologic active inflammation grades by using two-tailed t tests. Receiver operating characteristic curves were generated for mean normalized iodine density, CDAI, and HBI to determine sensitivity, specificity, and accuracy. A P value less than .05 was considered to indicate statistical significance. Results The following 16 patients were evaluated (mean age, 41 years ± 14 [standard deviation]): 10 patients (five men, five women; mean age, 41 years ± 15) with 19 surgical resection specimens and six patients with terminal ileum colonoscopic mucosal biopsies (four men, two women; mean age, 43 years ± 14). Mean normalized iodine density was 16.5% ± 5.7 for bowel segments with no active inflammation (n = 8) and 34.7% ± 9.7 for segments with any active inflammation (n = 17; P < .001). A 20% mean normalized iodine density threshold had sensitivity, specificity, and accuracy of 17 of 17 (100%; 95% CI: 80.5, 100), six of eight (75%; 95% CI: 35, 97), and 23 of 25 (92%; 95% CI: 74, 99), respectively, for active inflammation. Clinical indexes were similar for patients with and without active inflammation at histopathologic analysis (CDAI score, 261 vs 251, respectively [P = .77]; HBI score, 7.8 vs 6.4, respectively [P = .36]). Conclusion Iodine density from dual-energy CT enterography may be used as a radiologic marker of Crohn disease activity as correlated with histopathologic analysis. © RSNA, 2021 See also the editorial by Ohliger in this issue.

Crohn disease (CD) affects the small bowel in 80% of patients. Double balloon endoscopy (DBE) provides the potential for direct and extensive mucosal visualization with the potential for diagnostic monitoring and therapeutic intervention. This study aimed to investigate the safety and effectiveness of DBE in small-bowel CD.

From our DBE database, patients with CD at the time of index DBE (January 2004-January 2013) were identified. Data collection included demographics, CD phenotype (age at diagnosis, disease location, disease activity), procedural information, adverse events (perforation, pancreatitis, death), therapeutic intervention (stricture dilation), and outcome (escalation or maintenance of existing therapy, referral to surgery).

A total of 184 DBEs were performed in patients with inflammatory bowel disease over 162 endoscopic sessions. In this cohort, 115 patients had previously diagnosed CD. A diagnosis of CD was made in 22 patients. Of those with known CD, 140 DBEs were performed in 82 patients; DBE findings led to escalation of medical therapy in 26% of patients, maintenance of therapy in 26% of patients, and surgery in 18% of patients. We considered DBE to have failed in 11% (n = 18) of patients. During 46 endoscopic sessions, in 29 patients, 103 strictures were dilated via balloon dilation. Of patients undergoing dilation with clinical follow-up, 19 of 24 (79%) patients were surgery-free during the study period. Overall, there were 2 perforations.

We found that DBE is a safe and effective procedure in patients with suspected or established CD. Furthermore, patients undergoing dilation of strictures via DBE had an 80% surgery-free rate within the follow-up period.

The objective of this study was to determine if dual-energy computed tomography enterography (DECTE)-obtained iodine density can predict medical management change or surgery in Crohn disease patients.

The most active-appearing bowel segment on DECTE in 21 Crohn disease patients was retrospectively interrogated with prototype software determining the percentage of bowel wall (I) in specified ranges. Patients were categorized into 3 groups after DECTE: (1) no management change, (2) outpatient medication change, and (3) inpatient admission or surgery. Crohn's disease activity index was calculated. Group 3's percentage iodine density of >3 mg/mL and Crohn's disease activity index were compared with group 1/2. Crohn's disease activity index and percentage iodine density of >2 mg/mL were compared for groups 2/3 versus group 1 patients.

There were 5 group 1, 6 group 2, and 10 group 3 patients. Group 3 patients had higher frequency of iodine density >3 mg/mL (27%) compared with groups 1/2 patients (12.6%) (P < 0.05). Crohn's disease activity index was similar (P = 0.98). Groups 2/3 patients had 60.5% iodine density of >2 mg/mL, whereas group 1 patients had 31.7% iodine density of >2 mg/mL (P < 0.05). Crohn's disease activity index was similar (P = 0.12).

Iodine density from DECTE may predict medical or surgical Crohn disease management.

Fibrotic strictures are one of the most severe complications of Crohn's Disease (CD). They occur in about 50% of patients at five years and in 70% at ten years of the diagnosis. The only treatment available for symptomatic fibrotic strictures is surgical resection and endoscopic dilation. Both strategies are associated with a high rate of recurrence, and with multiple surgical resections, which pose the threat of surgical morbidity and short bowel syndrome. Therefore, it is crucial to identify, early, the patients more prone to develop intestinal fibrosis to intensify follow-ups, switch to more aggressive treatments, and suggest lifestyle modifications. Scarce data are available concerning biomarkers and genetic determinants to predict which patient will develop intestinal fibrosis. Biologic or clinical markers would be useful to determine this subgroup of CD patients and to predict the onset of intestinal fibrosis and, ideally, its severity. Furthermore, the identification of environmental risk factors may suggest lifestyle changes aimed at modifying the natural course, thus decreasing the risk of complicated CD. In this review, we will critically revise clinical, environmental, genetic, and serologic factors that have been associated with a complicated CD course with a particular focus on the fibrostenosing phenotype and their possible implications as predictive factors of intestinal fibrosis.

Postoperative recurrence of Crohn's disease is common and requires a multidisciplinary approach between surgeons and gastroenterologists in the perioperative and postoperative period to improve outcomes in this patient population. Endoscopic recurrence precedes clinical and surgical recurrence and endoscopic monitoring is crucial to guide postoperative management. Risk stratification of patients is recommended to guide early prophylactic management, and follow-up endoscopic monitoring can guide intensification of therapy. This review summarizes evidence behind postoperative recurrence rates, disease monitoring techniques, nonbiologic and biologic therapies available to prevent and treat postoperative recurrence, risk factors associated with recurrence, and postoperative management strategies guided by endoscopic monitoring.

Postoperative recurrence is frequently observed after ileocecal resection in Crohn's disease (CD) patients. Since 2010, endoscopy within 1 year is considered the gold standard for its diagnosis. However, if and how frequent such endoscopies are performed in clinical practice remains unknown.

We analyzed 1-year follow-up data on CD patients who underwent ileocecal resection between 2012 and 2014 and compared them with hospitalized, non-resected CD controls. Data were extracted from the Helsana database. Helsana is one of the largest Swiss health insurance companies providing coverage for 1.2 million individuals.

A total of 645 CD patients were identified with ≥1 hospitalization between 2012 and 2014 and a follow-up of 1 year. Of these, 79 (12.2%) underwent ileocecal resection. Although endoscopy rates increased over time and were higher in patients with resection versus controls (p = 0.029), in only 54.4% a 1-year follow-up ileocolonoscopy was performed. Postoperative prophylaxis with anti-tumor necrosis factor or azathioprine was prescribed in 63.3%. Female sex and age >60 years were independent predictors for not receiving prophylaxis (odds ratio [OR] 0.36, p = 0.048, and OR 0.2, p = 0.022). Patients with resection had significantly lower numbers of rehospitalizations (1.2 vs. 1.8, p = 0.021), with resection being an independent negative predictor for number of rehospitalizations in a Poisson regression model (incident risk ratio 0.64, p = 0.029). However, disease-related surgery was more often the cause for rehospitalization after resection versus controls (47.6 vs. 22.1%, p = 0.015). Total and inpatient health-care costs were higher in these patients.

Endoscopies are underused after ileocecal resection. This contrasts current guidelines. Physicians should be aware of this underuse and perform follow-up examinations more often.

CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points.

The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test.

The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization.

This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD.

Inflammatory bowel disease (IBD) is a chronically relapsing disease with a continuous need for proactive monitoring to decide appropriate treatments and follow-up strategies. To date, gastrointestinal endoscopy with histologic examination of biopsies and contrast-enhanced imaging are mandatory techniques for the diagnosis and the activity assessment of IBD.

In recent decades, many research efforts in the IBD field have been placed on finding non-invasive and reliable biomarkers of disease burden that can be easily tested in body fluids without impacting the quality of life of patients. Unfortunately, the ideal biomarker is yet to be discovered and recent studies have investigated the possibility to increase the accuracy of such measurements by combining different markers. In this review, we provide an update about the current knowledge on biomarkers of intestinal inflammation in IBD, focussing on disease diagnosis, correlation with endoscopic findings, and prediction of relapse. We also summarize composite scores of clinical and laboratory markers that have been recently proposed in various scenarios of disease activity. Key Messages: To date, only C-reactive protein and faecal calprotectin can be considered reliable markers of disease activity with demonstrated utility in IBD management. The combination of different parameters has recently shown higher accuracy and might substitute single-marker approaches in the future of research and clinical practice.

Prevention and management of postoperative recurrence (POR) is a controversial field in Crohn's disease. The aim of this survey was to report common practice in real-life settings.

An 11-question survey was distributed among gastroenterologists attending the 14th European Crohn's and Colitis Organisation (ECCO) congress.

Postoperative endoscopy to assess recurrence was routinely performed within 12 months by 87% of respondents. Forty-six percent of clinicians reported to maintain endoscopic assessment in routine follow-up even after first negative colonoscopy. Most respondents (60%) considered starting postoperative immunoprophylaxis in naïve patients if one or more known risk factors were present. The number of risk factors was an important driver for prescribing biologics over immunosuppressants for 60% of respondents.In case of fistulizing phenotype, perianal disease, or concomitant colonic involvement, the majority of physicians reported to start an immediate prophylaxis in 85, 98 and 88% of patients, respectively. A significant percentage of clinicians were more prone to an endoscopy-driven treatment in long-standing disease after failure of thiopurines (51%) and elderly (43%).

Endoscopy within the first year after surgery to assess POR has become routine in most centres. The high rate of early prophylaxis with expensive biologics despite missing solid evidence highlights the need for more randomized trials.