P694 Long-term monitoring of post-surgical recurrence in Crohn’s disease using a strategy based on the periodic determination of fecal calprotectin in patients without early postoperative recurrence

The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence

Small bowel capsule endoscopy (SBCE) is a noninvasive method to detect endoscopic postoperative recurrence (POR) after an ileocolonic resection in Crohn's Disease (CD). Few studies have evaluated the role of SBCE in the early POR (= 12 months). Data for detection of late POR (>12 months) and evaluation of treatment response in previous POR is scarce. We aimed to assess the SBCE performance in the three scenarios (early-POR, late-POR, and previous-POR). Retrospective 11-year cohort study of SBCE procedures performed on CD patients with ileocolonic resection. Disease activity by Rutgeerts score (RS), correlation with biomarkers, and therapeutic changes were recorded. We included 113 SBCE procedures (34 early-POR, 44 late-POR, and 35 previous-POR). 105 procedures (92.9%) were complete and 97 SBCE (85.5%) were conclusive with no differences between groups. Relevant POR (RS ≥i2) was more frequent in the early-POR group compared to late-POR (58.8% vs 27.3%, p=0.02). In the previous-POR, RS improved in 43.5% of procedures, worsened in 26%, and remained unchanged in 30.5%. Fecal calprotectin (FCP) value of 100µg/g displayed the best accuracy: sensitivity 53.8%, specificity 78.8%, positive predictive value 66.7% and negative predictive value 68.4%. SBCE guided therapeutic changes in 43 patients (38%). No adverse events occurred in our cohort. SBCE is a safe and effective method to assess POR in the early and late setting in clinical practice, and for the evaluation of treatment response to previous POR. FCP is an accurate surrogate marker of POR and 100µg/g value had the best overall accuracy.

Which Diet for Crohn’s Disease? Food for Thought on the Specific Carbohydrate Diet, Mediterranean Diet, and Beyond

Postoperative Crohn's Disease Recurrence: Time to Adapt Endoscopic Recurrence Scores to the Leading Surgical Techniques

Noninvasive Assessment of Postoperative Disease Recurrence in Crohn’s Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease

Infliximab treatment of postoperative ulcers in Crohn's disease: to inject or not to inject—that is the question

fecal calprotectin is a selection tool prior to endoscopic studies in patients with gastrointestinal symptoms. However, some symptomatic patients with altered fecal calprotectin will not have any endoscopic lesions. The aim of the study was to determine the factors associated with the presence of altered fecal calprotectin in patients with negative endoscopic studies of the colon and small bowel. this was an observational, prospective study of patients with digestive symptoms. The association of different clinical factors with elevated fecal calprotectin in the absence of endoscopic lesions of the colon and small bowel were analyzed. 143 patients were included in the study, 98 were female (68.5 %) and the mean age was 40.06 ± 16.42 (15-82) years. Smoking and non-steroidal anti-inflammatory drug intake were associated with altered fecal calprotectin in patients with a negative endoscopy of the colon and small bowel (p = 0.029 and p = 0.006). The mean values of fecal calprotectin were significantly higher in smokers, users of non-steroidal anti-inflammatory drugs and patients with small intestine bacterial overgrowth. Smoking (OR: 3.505; p = 0.028), non-steroidal anti-inflammatory drugs intake (OR: 3.473; p = 0.021) and small intestine bacterial overgrowth (OR: 3.172; p = 0.013) were independent risk factors for altered fecal calprotectin in the absence of endoscopic lesions. No association was found for any of the other variables. smoking and the use of non-steroidal anti-inflammatory drugs are strongly associated with elevated levels of fecal calprotectin in symptomatic patients with a negative colonoscopy and capsule endoscopy of the small bowel. Small intestine bacterial overgrowth is also associated.

Fecal calprotectin (FC) is a widely used noninvasive marker of gut inflammation that is associated with endoscopic severity in Crohn's disease (CD). However, FC has been inconsistent in predicting postoperative recurrence of CD, and its utility in the postoperative setting remains unclear. Blood and fecal samples were collected in consecutively recruited patients with CD who had undergone ileocolonic resection and required a colonoscopy to assess postoperative recurrence, as defined by the Rutgeerts score (RS). A total of 86 patients were prospectively recruited at five centers. Overall, 49 (57%) had CD recurrence (RS≥i2). FC concentrations trended to increase with RS severity; FC median (interquartile range) was significantly higher in patients with endoscopic recurrence than those in endoscopic remission [172.5 (75-375) vs. 75 (36.5-180.5) μg/g, respectively]. The same occurred for C-reactive protein (CRP) [0.5 (0.1-0.95) vs. 0.1 (0.02-0.27)] mg/dl and the Harvey-Bradshaw index (HBI) [4 (2-7) vs. 1 (0-3.5)]. The three variables significantly correlated. The area under the curve to discriminate between patients in endoscopic remission and recurrence was 0.698 for FC, with 62 μg/g being the optimal cut-off point. This indicated FC would have 85.7% sensitivity and 45.9% specificity in detecting any recurrence, having positive predictive value and negative predictive value of 67.7 and 70.8%, respectively. Area under the curve for CRP and HBI were both 0.710. The combination of CRP and HBI provided a positive predictive value 95.7 and a diagnostic odds ratio of 30.8. FC is not better than CRP combined with HBI to predict endoscopic postoperative recurrence of CD.

The perioperative behavior of fecal calprotectin and whether it predicts early postoperative endoscopic recurrence of Crohn's disease are unknown. We aimed to compare the perioperative profiles of fecal calprotectin between patients with Crohn's disease and patients without Crohn's disease undergoing intestinal resection and to identify the association between consecutive fecal calprotectin levels and endoscopic recurrence 3 months after surgery in patients with Crohn's disease. This was a prospective observational study. This study was conducted in a tertiary referral hospital. One hundred fourteen consecutive patients (90 Crohn's disease, 24 non-Crohn's disease) who underwent resection were recruited. Univariate and multivariate analyses were performed to identify variations and risk factors. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves. The fecal calprotectin levels on preoperative day 14 and postoperative days 14, 21, 28, 60, and 90 were higher in the Crohn's disease group than they were in non-Crohn's disease group (p < 0.05). Twenty patients (22.2%) developed endoscopic recurrence 3 months after resection. The trend for fecal calprotectin change (Δfecal calprotectin) from preoperative day 14 to postoperative day 14 was opposite in the recurrence and nonrecurrence groups. Multivariate analysis showed that this change was a predictive factor of early endoscopic recurrence (p < 0.05). ΔFecal calprotectin was more accurate at predicting early endoscopic recurrence than was fecal calprotectin at single time points with a cutoff value of 240 μg/g. This is a single-center trial with a limited cohort of patients. The perioperative fecal calprotectin levels were higher in patients with Crohn's disease than they were in the control group. The change in fecal calprotectin levels from preoperative day 14 to postoperative day 14 could serve as a practical predictive index for early postoperative endoscopic recurrence. See Video Abstract at http://links.lww.com/DCR/A796.

Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis. A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population. The mean FCAL (µg/g) level in healthy control (n = 5), stable cirrhotics (n = 10), ESLD (n = 10) and ACLF (n = 10) patients was 109.2 (95% CI: - 53.39 to 271.79), 143.3 (95% CI: 50.5-236.45), 176.9 (95% CI: 122.93-230.87) and 543.5 (95% CI: 207.09-879.91) (p = 0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p = 0.005) and FCAL ≥ 200µg/g (OR = 10.8, p = 0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) μg/g,p = 0.005. FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of ≥ 200µg/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality.

Mesalamine Dose Escalation Reduces Fecal Calprotectin in Patients With Quiescent Ulcerative Colitis

Background Recurrence of Crohn’s disease (CD) after ileocolic resection is common. However, reliable non-invasive monitoring methods are lacking, for instance, the use of faecal calprotectin (FC) has showed inconsistent results in this subgroup of patients. The aim of this study was to evaluate clinical and biochemical factors associated with post-operative endoscopic recurrence in CD patients. Methods Retrospective single-center study including patients with CD who underwent ileocolonoscopy for CD surveillance, after ileocolic resection. The patients’ clinical status was evaluated through Harvey-Bradshaw index (HBI), with clinical remission considered as ≤ 4 points. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and FC. Clinical and biochemical parameters were evaluated in the 6 months prior to ileocolonoscopy. Post-operative endoscopic recurrence was defined as a Rutgeerts score ≥ i2b. Results A total of 81 patients and 121 ileocolonoscopies were included. Most patients were female (55.6%), with a mean age of 48±13 years. Regarding the Montreal classification, 37 patients had ileal disease (45.7%) and 44 ileocolonic disease (54.3%); 9 patients had nonstricturing, nonpenetrating disease (11.1%), 35 stricturing (43.2%) and 37 penetrating disease (45.7%). Nineteen patients had perianal disease (23.5%). The mean time between the surgery and the endoscopic evaluation was 135±79 months. Post-operative endoscopic recurrence was observed in 52 ileocolonoscopies (43.0%). Symptomatic patients (HBI &amp;gt; 4 points) were 11 times more likely to have post-operative endoscopic recurrence (OR 10.686, 95%CI 2.930-38.974, p&amp;lt;0.001). Those with post-operative endoscopic recurrence had a significantly higher FC values (median 189 vs 69 µg/g, p&amp;lt;0.001) and higher ESR values (median 14 vs 9 mm, p=0.002). In fact, patients with FC values ≥ 150 µg/g and those with ESR values &amp;gt; 12 mm were 4 and 3 times more likely to have post-operative endoscopic recurrence (OR 3.654, 95%CI 1.605-8.316, p=0.002 and OR 3.059, 95%CI 1.397-6.696, p=0.005, respectively). The presence of post-operative endoscopic recurrence was not associated with CRP values (median 2.9 vs 2.9 mg/L, p=0.466), and neither with mean time between the surgery and the endoscopic evaluation (mean 126±83 vs 142±75 months, p=0.263). Conclusion The presence of symptoms (HBI &amp;gt; 4 points), FC values ≥ 150 µg/g and ESR values &amp;gt; 12 mm was associated with post-operative endoscopic recurrence in CD. Therefore, the HBI, FC and ESR values can be used to monitor CD patients after ileocolic resection, and prompt endoscopic evaluation should be performed in those with HBI &amp;gt; 4 points, FC values ≥ 150 µg/g and/or ESR values &amp;gt; 12 mm.

Background Ileocecal resection with an ileocolic anastomosis is the most common surgical procedure for Crohn’s disease (CD).1 Today’s leading surgical techniques, the (Kono-S) side-to-side and side-to-end anastomosis, have introduced new anatomical locations.2 Furthermore, lesions at the ileal inlet, corresponding to the critical diameter proximal to the anastomotic line, have been suggested to be associated with a higher risk of postoperative recurrence.1-3 The aim of our study was to evaluate the risk of postoperative recurrence according to the anatomical location of the lesions. Methods We conducted a retrospective analysis of 85 patients with CD after ileocecal resection (47% male, median age 33 years). All patients underwent a video-recorded ileocolonoscopy within 14 months of resection, which were centrally scored by eight expert endoscopists with the updated Rutgeerts score (URS) and a granular score per anatomical location (anastomotic line, ileal blind loop, ileal body, ileal inlet and neo-terminal ileum). The development of clinical postoperative recurrence (cPOR) was assessed. cPOR was defined as presence of CD-related symptoms combined with at least one of the following: C-reactive protein &amp;gt;5 mg/L, faecal calprotectin &amp;gt;250 µg/g, endoscopic recurrence (Rutgeerts score of ≥ i2b), or radiological signs of neoterminal ileitis. Patients that underwent treatment optimization based on this index ileocolonoscopy were excluded. We used Cox regression models to assess the association between granular endoscopic scores and cPOR. Models were adjusted for either the dichotomised or categorised URS and for postoperative prophylactic therapy. Results The majority of patients (84%) underwent an ileocecal resection with isoperistaltic side-to-side anastomosis. The median (interquartile range, IQR) time from ileocolonic resection to first postoperative ileocolonoscopy was 6.21 (5.88-7.00) months. During a median follow-up of 6.15 (4.91-8.07) years, 47% of patients developed cPOR. Analysis of the granular endoscopic scoring revealed that presence of lesions at the ileal inlet was associated with an increased risk of cPOR. Statistically significant association were observed for the deep aphthoid lesions [hazard ratio 1.96 (95% confidence interval 1.02-3.77), p = 0.045], punctiform lesions [HR 1.96 (1.02-3.77), p = 0.045], deep ulcerations [HR 3.23 (1.33-7.83), p = 0.01] and large superficial ulcerations [HR 2.89 (1.12-7.39), p = 0.029]. In contrast, no significant associations were observed with lesions in other locations. (Table 1) Conclusion The significant association between ileal inlet lesions and cPOR underscores the importance of incorporating new anatomical locations into endoscopic scoring systems, supporting the broader application of the URS.

BackgroundCalprotectin is a heat stable intracellular protein shed by neutrophils into the intestinal lumen in response to inflammation. Lack of specificity makes its role in the assessment of inflammatory bowel...

Introduction Faecal calprotectin (FC) is a stool biomarker recommended as a simple, non-invasive test to distinguish between inflammatory bowel disease (IBD) and functional bowel disorders. Despite a good correlation with colonic inflammation, FC is felt to be less accurate at identifying small bowel (SB) inflammation. Small bowel capsule endoscopy (SBCE) has a high sensitivity for detecting SB mucosal inflammation. We investigated the correlation between FC and SBCE in patients with suspected IBD. Method We prospectively correlated the findings of SBCE with FC levels in patients under investigation for suspected IBD. Patient demographics, clinical symptoms, medications and blood parameters: haemoglobin (Hb), albumin, ESR and CRP were collected. SBCE findings including Lewis scores were analysed against FC values and final diagnosis. Results 127 patients were included, mean age 42 years (range 18–75 years), 85 female. Presenting symptoms included: a combination of diarrhoea, abdominal pain and bloating (74%), diarrhoea alone (13%), abdominal pain alone (12%), rectal bleeding (1%). Median time from FC measurement to SBCE was 62 days. 12% had a family history of IBD, 14% were current smokers. 6 patients with a diagnosis of colonic pathology were excluded. Results are presented in Table 1. Of the 61 patients with FC >100 µg/g, 14 (23.0%) had clinically significant SB findings (12 SB ulcers, 2 villous atrophy) and mean FC levels 468 µg/g (range 112–1010 µg/g). Overall a definitive diagnosis was made in 10 patients (9 Crohn’s disease, 1 NSAID enteropathy), the remaining 10 patients are undergoing further evaluation. FC >50 µg/g was significantly associated with clinically relevant SBCE findings (χ² p = 0.02). FC had a sensitivity 81%, specificity 40%, positive predictive value 42% and negative predictive value (NPV) 80%. Receiver operating curve analysis showed an area under the curve (AUC) of 0.626 for FC, similar to CRP (AUC 0.638) but better than ESR (AUC 0.524) and Hb (AUC 0.545). Albumin most closely correlated with an AUC 0.686. Multiple logistical regression showed serum albumin to be the only variable significantly associated with positive SBCE (p = 0.032). Lewis score significantly correlated with FC value (r = 0.793, p Conclusion With a reasonable sensitivity and NPV, FC could be most effectively utilised to screen out patients where further SB investigation is unnecessary. However, in our series 1 patient with FC ≤50 µg/g had SB Crohn’s disease. Thus at best, FC can be only be recommended as an adjunct to clinical decision making, when patient factors and other biochemical parameters are also taken into account. Disclosure of interest None Declared.