Early Postoperative Endoscopic Recurrence Research Articles

Clinical Predictors of Early and Late Endoscopic Recurrence Following Ileocolonic Resection in Crohn's Disease.

Multiple factors are suggested to place Crohn's disease patients at risk of recurrence after ileocolic resection with conflicting associations. We aimed to identify clinical predictors of recurrence at first [early] and further [late] postoperative colonoscopy. Crohn's disease patients undergoing ileocolic resection were prospectively recruited at six North American centres. Clinical data were collected and endoscopic recurrence was defined as Rutgeerts score ≥i2. A multivariable model was fitted to analyse variables independently associated with recurrence. A total of 365 patients undergoing 674 postoperative colonoscopies were included with a median age of 32 years, 189 [51.8%] were male, and 37 [10.1%] were non-Whites. Postoperatively, 133 [36.4%] used anti-tumour necrosis factor [anti-TNF] and 30 [8.2%] were smokers. At first colonoscopy, 109 [29.9%] had recurrence. Male gender (odds ratio [OR] = 1.95, 95% confidence interval [CI] 1.12-3.40), non-White ethnicity [OR = 2.48, 95% CI 1.09-5.63], longer interval between surgery and colonoscopy [OR = 1.09, 95% CI 1.002-1.18], and postoperative smoking [OR = 2.78, 95% CI 1.16-6.67] were associated with recurrence, while prophylactic anti-TNF reduced the risk [OR = 0.28, 95% CI 0.14-0.55]. Postoperative anti-TNF prophylaxis had a protective effect on anti-TNF experienced patients but not on anti-TNF naïve patients. Among patients without recurrence at first colonoscopy, Rutgeerts score i1 was associated with subsequent recurrence [OR = 4.43, 95% CI 1.73-11.35]. We identified independent clinical predictors of early and late Crohn's disease postoperative endoscopic recurrence. Clinical factors traditionally used for risk stratification failed to predict recurrence and need to be revised.

Komentář ke článku „The influence of microscopic inflammation at resection margins on early postoperative endoscopic recurrence after ileocaecal resection for Crohn’s disease“

Komentář ke článku „The influence of microscopic inflammation at resection margins on early postoperative endoscopic recurrence after ileocaecal resection for Crohn’s disease“

Ileocolonic End-to-End Anastomoses in Crohn’s Disease Increase the Risk of Early Post-operative Endoscopic Recurrence in Those Undergoing an Emergency Resection

Background and AimSeveral risk factors affecting post-operative recurrence in Crohn’s disease patients have been studied, and of these, the role of the anastomosis remains contentious. We aimed to compare the risk of developing early post-operative endoscopic recurrence (EPER), in resections that had an end-to-end anastomosis (ETEA) to a side-to-side anastomosis (STSA). MethodsAll Crohn’s disease patients that underwent an ileocolic or small bowel resection between January 2012 and June 2017 at two tertiary IBD centres were reviewed retrospectively. Included patients had a minimum of 12-month clinical follow-up and a colonoscopy within 12 months of the resection or stoma reversal. Univariate and multivariate binary logistic regression analyses determined the independent risk factors for early post-operative endoscopic recurrence, defined as a Rutgeerts score of ≥ i2b. ResultsNinety-two resections associated with an ETEA or a STSA were included for analysis. The ETEA was the most common anastomosis, constructed in 55 patients (59.8%). Forty-nine operations (53.3%) resulted in a ≥ i2b recurrence at the first surveillance colonoscopy. The multivariate analysis showed that there was no difference between the ETEA and STSA in determining the odds ratio (OR) for developing EPER (OR = 2.41 (0.95–6.05), P = 0.06). In those that underwent a resection emergently however, the significant determinants of EPER were as follows: having an ETEA (OR = 38.12 (2.44–595.87), P = 0.01), failing to commence a biologic and/or an immunosuppressant early (OR = 24.21 (1.69, 347.81), P = 0.02), and active smoking (OR = 7.19 (1.12–46.21), P = 0.04). ConclusionThe ETEA is best avoided in those undergoing an emergency resection. The early commencement of a biologic and/or an immunosuppressant and smoking cessation is imperative this high-risk group of patients.

Early Postoperative Endoscopic Recurrence in Crohn's Disease Is Characterised by Distinct Microbiota Recolonisation.

Background and AimsIntestinal microbiota dysbiosis is implicated in Crohn’s disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota.MethodsMucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts score ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms.ResultsThe mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR] <0.01) and enrichment of Proteobacteria [FDR = 0.009] and Akkermansia spp. [FDR = 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDR <0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDR <0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDR = 0.003] and Actinomycineae [FDR = 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDR = 0.04] and Fusobacteria [FDR = 0.04] compared with patients without POR.ConclusionsMicrobiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.

The Influence of Microscopic Inflammation at Resection Margins on Early Postoperative Endoscopic Recurrence After Ileocaecal Resection for Crohn's Disease.

The pathogenesis and risk factors for early postoperative endoscopic recurrence of Crohn's disease [CD] remain unclear. Thus, this study aimed to identify whether histological inflammation at the resection margins after an ileocaecal resection influences endoscopic recurrence. We have prospectively followed up patients with CD who underwent ileocaecal resection at our hospital between January 2012 and January 2018. The specimens were histologically analysed for inflammation at both of the resection margins [ileal and colonic]. We evaluated whether histological results of the resection margins are correlated with endoscopic recurrence of CD based on colonoscopy 6 months after ileocaecal resection. Second, we assessed the influence of known risk factors and preoperative therapy on endoscopic recurrence of CD. A total of 107 patients were included in our study. Six months after ileocaecal resection, 23 patients [21.5%] had an endoscopic recurrence of CD. The histological signs of CD at the resection margins were associated with a higher endoscopic recurrence [56.5% versus 4.8%, p < 0.001]. Disease duration from diagnosis to surgery [p = 0.006] and the length of the resected bowel [p = 0.019] were significantly longer in patients with endoscopic recurrence. Smoking was also proved to be a risk factor for endoscopic recurrence [p = 0.028]. Histological inflammation at the resection margins was significantly associated with a higher risk of early postoperative endoscopic recurrence after an ileocaecal resection for CD.

Crohn's Disease Mucosal Transcriptomes Highlight JAK/STAT Pathway Involvement in Postoperative Recurrence

Background: Crohn's disease displays heterogeneity in terms of disease location, progression and response to treatment. Most patients require an intestinal resection due to complicated disease, and a majority of them will experience disease recurrence. We aimed to characterize biological pathways driving postoperative recurrence and to identify predictors which could guide therapeutic management. Methods: In this multicentre prospective study, we conducted transcriptome analysis on ileal mucosa of CD patients undergoing ileocolonic resection. Samples were collected from the most inflamed part of the ileum (n=200), from the ileal resection margin (n=149) and in the neo-terminal ileum 6 months after surgery (n=122). The primary endpoint was postoperative endoscopic recurrence at month 6. We applied a regression model to identify gene signatures predicting for endoscopic recurrence. Findings: Molecular patterns of early endoscopic recurrence significantly differed from those observed in chronic inflammation. Gene expression analysis of the inflamed area of the surgical specimens identified clusters of CD patients. However, pathway gene signatures at the ileal margin were superior to those of the inflamed area to predict postoperative outcome. Several pathways, including JAK/STAT signalling, cell adhesion molecules and extracellular matrix protein were associated with a higher risk of endoscopic recurrence. JAK/STAT pathway activation at the ileal margin predicted early postoperative endoscopic recurrence (AUC of 0*74) and was associated with a higher of clinical relapse on the long term. A significant increase of p-STAT3 levels at the ileal margin was associated with severe endoscopic recurrence (i3, i4) compared to no recurrence (i0) (p=0*02) and moderate recurrence (i1, i2) (p=0*04). Interpretation: Gene expression analysis at the ileal margin of the surgical specimen may strongly predict postoperative outcome. The inflammatory processes associated with postoperative recurrence differ from those engaged in chronic inflammation. Activation of JAK/STAT signalling at the ileal margin of the surgical specimen is predictive of postoperative recurrence and should be specifically targeted. Trial Registration: ClinicalTrials.gov (NCT03458195). Funding Statement: This work was supported by Helmsley Charitable Trust and the Institut national de sante et de la recherche biomedical (INSERM). Declaration of Interests: SN received honoraria from MSD, Abbvie, Takeda, Janssen, HAC Pharma, Tillots, Ferring, and Novartis. BP received honoraria from AbbVie, MSD, Takeda, Janssen, Bioagaran, and Ferring. AB received honoraria from MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Sanofi-Aventis, Hospira, and Janssen. XT received honoraria from Abbvie, MSD, Takeda, Ferring, Norgine, and Janssen. MF received honoraria from AbbVie, MSD, Takeda, Janssen, Pfizer, Ferring, and Boehringer. PS received honoraria from Takeda, MSD, Biocodex, Ferring and Abbvie and financial support from Takeda. MA received honoraria from Janssen, Takeda, Pfizer, MSD, Abbvie, Ferring, Amgen, Biogen, Celgene, and Genentech/Roche. All other authors have no conflict of interest regarding this study. Ethics Approval Statement: All patients provided an informed written consent. The study was approved by AFFSAPS (IDRCB: 2009-A00205-52) and the French Ethic Committee (CPP 2009/17).

Profile of Consecutive Fecal Calprotectin Levels in the Perioperative Period and Its Predictive Capacity for Early Endoscopic Recurrence in Crohn's Disease.

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.

Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn's disease: results from a prospective cohort study.

After ileocaecal resection for Crohn's disease (CD), inflammatory lesions frequently recur on the anastomosis and/or on the neo-terminal ileum. To identify predictors of early post-operative endoscopic recurrence. From September 2010 to September 2017, the REMIND group conducted a prospective nationwide study in nine French academic centres. Data were collected at the time of surgery and endoscopy, performed 6-12months after surgery. Endoscopic recurrence was defined as a Rutgeerts score ≥i2. Baseline factors associated with endoscopic recurrence were searched by univariate and multivariate regression analysis. Two hundred and eighty-nine CD patients were included. Endoscopy within 1year following surgery was performed in 225 (78%) patients (104M/121F). Mean age and disease duration were 35 (12.2) and 8.8 (8.9) years respectively. Seventy (32%) patients were active smokers at surgery. One hundred and forty-two (63%) patients received at least one anti-TNF therapy before surgery. After surgery, 40 (18%) patients received thiopurines and 66 (29%) received an anti-TNF agent. Endoscopic recurrence occurred in 107 (47%) patients. In multivariate analysis, male gender (OR=2.48 [IC 95% 1.40-4.46]), active smoking at surgery (OR=2.65 [IC 95% 1.44-4.97]) and previous resection (OR=3.03 [IC 95% 1.36-7.12]) were associated with a higher risk of endoscopic recurrence. Inversely, post-operative anti-TNF treatment decreased the risk of endoscopic recurrence (OR=0.50 [IC 95% 0.25-0.96]). Male gender, active smoking at surgery and previous intestinal resection are associated with a higher risk of endoscopic post-operative recurrence, while post-operative anti-TNF treatment is associated with a lower risk.

Factors affecting the incidence of early endoscopic recurrence after ileocolonic resection for Crohn's disease: a multicentre observational study.

Early endoscopic recurrence is frequently observed in patients following resection for Crohn's disease (CD). However, factors affecting the incidence of an early postoperative endoscopic recurrence (EPER) have not been fully determined. The aim of this study was to evaluate risk factors for EPER after ileocolonic resection for CD. This was a retrospective, international multicentre study, in which 127 patients with a first ileocolonoscopy conducted between 6 and 12months after ileocolonic resection for CD were included. Endoscopic recurrence was defined as a Rutgeerts score of ≥i2. The following variables were investigated as potential risk factors for EPER: gender, age at surgery, location and behaviour of CD, smoking, concomitant perianal lesions, preoperative use of steroids, immunomodulators and biologics, previous resection, blood transfusion, surgical procedure (open vs laparoscopic approach), length of resected bowel, type of anastomosis (side-to-side vs end-to-end), postoperative complications, granuloma and postoperative biological therapy. Variables related to the patient, disease and surgical procedure were investigated as potential risk factors for EPER, withunivariate and multivariate (logistic regression) analyses. 43/127 (34%) patients had EPER at the time of the first postoperative ileocolonoscopy. In univariate analysis, only preoperative steroid use was significantly associated with a higher rate of EPER [21/45 patients (47%) on steroids and 22/82 patients (27%) without steroids (P=0.04)]. In multivariate analysis, only preoperative steroid use was a significant independent risk factor for EPER (odds ratio 3.28, 95% confidence interval: 1.30-8.28; P=0.01). This study found that only preoperative steroid use was a significant risk factor for EPER after ileocolonic resection for CD. Prospective studies are necessary to evaluate precisely the impact of perioperative medications on EPER rates.

DOP008. Plexitis as a predictive factor for early post-operative endoscopic recurrence in patients with Crohn's disease undergoing a right hemicolectomy with ileocolonic anastomosis: Results from a prospective, single center trial.

DOP008. Plexitis as a predictive factor for early post-operative endoscopic recurrence in patients with Crohn's disease undergoing a right hemicolectomy with ileocolonic anastomosis: Results from a prospective, single center trial.

Su1375 Direct Retrospective Comparison of Adalimumab and Infliximab in Preventing Early Postoperative Endoscopic Recurrence After Ileocecal Resection for Crohn's Disease: Results From the Multiper Database

Su1375 Direct Retrospective Comparison of Adalimumab and Infliximab in Preventing Early Postoperative Endoscopic Recurrence After Ileocecal Resection for Crohn's Disease: Results From the Multiper Database

Su1376 Retrospective Comparison of the Efficacy of Anti-TNF Agents in Isolation or Combined With Azathioprine in Prevention of Early Postoperative Endoscopic Recurrence in Crohn's Disease From the Multiper Database

collagenous band thickness, and lamina propria inflammation. Hazard ratios (HR) were calculated by logistic regression analysis with 95% confidence intervals. Results: The overall symptom relapse rate was 61%. By multivariate analysis, a baseline stool frequency >5/day (HR 3.95; 1.08 14.39), a history of diarrhea >12 months (HR 1.77; 1.04 3.03), and the absence of budesonide maintenance therapy (HR 2.71; 1.37 5.38) were associated with symptom relapse. The time to relapse was shorter in patients with a baseline stool frequency >5/day (56 vs. 199 days, p = 0.024), as in those with a history of diarrhea >12 months (56 vs. 220 days, p = 0.009). Budesonide maintenance therapy delayed the time to relapse (56 versus 207 days, p = 0.005). Conclusions: Our data demonstrate that a high stool frequency at baseline and a long duration of diarrhea are risk factors for symptom relapse in collagenous colitis, while budesonide maintenance therapy is a protective factor against symptom relapse.

Su1377 Does the Location of an IBD Centre Impact the Rates of Early Postoperative Endoscopic Recurrence After Ileocecal Resection in Crohn's Disease? Results From the Multiper Database

Direct Retrospective Comparison of Adalimumab and Infliximab in Preventing Early Postoperative Endoscopic Recurrence After Ileocecal Resection for Crohn's Disease: Results From the Multiper Database Paulo G. Kotze, Yasuo Suzuki, Takayuki Yamamoto, Silvio Danese, Rogerio Saad-Hossne, Idblan C. Albuquerque, Fabio V. Teixeira, Rodolff N. Silva, Ivan F. Barcelos, Marcia Olandoski, Lorete M. Kotze, Akihiro Yamada, Antonino Spinelli

Early post-operative endoscopic recurrence in Crohn's disease patients: Data from an Italian Group for the study of inflammatory bowel disease (IG-IBD) study on a large prospective multicenter cohort

IntroductionThe incidence of endoscopic recurrence (ER) in Crohn's disease following curative resection is up to 75% at 1year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1year seems to predict a clinical relapse. MethodsThe aim of this prospective study was to evaluate the incidence of early ER 6months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2weeks after surgery. ResultsSix months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p=0.04; OR 0.52, 95% CI 0.277–0.974). ConclusionIn this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6months instead of 1year to allow an adequate early treatment.

P511 Does the location of an IBD centre impact the rates of early postoperative endoscopic recurrence after ileocecal resection in Crohn's disease? Results from the MULTIPER database

P511 Does the location of an IBD centre impact the rates of early postoperative endoscopic recurrence after ileocecal resection in Crohn's disease? Results from the MULTIPER database

P519 Direct retrospective comparison of adalimumab and infliximab in preventing early postoperative endoscopic recurrence after ileocecal resection for Crohn's disease: results from the MULTIPER database

P519 Direct retrospective comparison of adalimumab and infliximab in preventing early postoperative endoscopic recurrence after ileocecal resection for Crohn's disease: results from the MULTIPER database

P512 Disseminated granuloma annulare associated with Crohn's disease: a rare extraintestinal manifestation

P511 Does the location of an IBD centre impact the rates of early postoperative endoscopic recurrence after ileocecal resection in Crohn’s disease? Results from the MULTIPER database P.G. Kotze1 *, T. Yamamoto2, S. Danese3, Y. Suzuki4, I. Albuquerque5, I. Barcelos1, L. Kotze6, M. Olandoski7, F. Teixeira8, R. Silva1, M. Sacchi9, A. Yamada4, R. SaadHossne10, A. Spinelli9,11. 1Cajuru University Hospital Catholic University of Parana, Colorectal Surgery Unit, Curitiba, Brazil, 2Yokkaichi Social Insurance Hospital, IBD Unit, Yokkaichi, Japan, 3Humanitas Research Hospital, IBD Unit Gastroenterology, Milano, Italy, 4Toho University Sakura Medical Center, Internal Medicine, Chiba, Japan, 5Heliopolis Hospital, IBD unit, Sao Paulo, Brazil, 6Cajuru University Hospital Catholic University of Parana, Gastroenterology, Curitiba, Brazil, 7Catholic University of Parana, Statistics, Curitiba, Brazil, 8Gastrosaude, Colorectal Surgery, Marilia, Brazil, 9Humanitas Research Hospital, Medical Biotechnologies and Translational Medicine, Milano, Italy, 10Sao Paulo State University, Digestive Surgery Department, Botucatu, Brazil, 11Humanitas Research Hospital, IBD Surgery Unit, Milano, Italy

P362 Retrospective comparison of the efficacy of anti-TNF agents in isolation or combined with azathioprine in prevention of early postoperative endoscopic recurrence in Crohn's disease from the MULTIPER database

P362 Retrospective comparison of the efficacy of anti-TNF agents in isolation or combined with azathioprine in prevention of early postoperative endoscopic recurrence in Crohn's disease from the MULTIPER database

Sa1270 Early Post-Operative Endoscopic Recurrence in Crohn's Disease Patients: Data From a Large Prospective Italian Multicenter Cohort

Sa1270 Early Post-Operative Endoscopic Recurrence in Crohn's Disease Patients: Data From a Large Prospective Italian Multicenter Cohort

Clinical, serological and genetic predictors of inflammatory bowel disease course

Patients with extensive or complicated Crohn's disease (CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines. In patients with localized and uncomplicated CD at diagnosis, early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact. In this context, there is a need for predictors of benign or unfavourable subsequent clinical course, in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions. At diagnosis, an age below 40 years, the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course. The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts. Consequently, the use of these predictors can be integrated into the elements that influence individual decisions. In the CD postoperative context, keeping smoking and history of prior resection are the strongest predictors of disease symptomatic recurrence. However, these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice. In ulcerative colitis (UC), extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease, and also with long-term colectomy and colorectal inflammation-associated colorectal cancer. In patients with extensive UC at diagnosis, a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered. At the moment, no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.