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

<b><i>Introduction:</i></b> Endoscopy remains the exam of choice in the evaluation of activity in Crohn’s disease (CD) after surgery (ACD-AS). However, intestinal ultrasound (IUS) may represent a noninvasive alternative. The objective of this study is to determine the diagnostic accuracy of this modality compared to endoscopy. <b><i>Material and Methods:</i></b> This is a cross-sectional study, comprising a period of 14 months, carried out in patients with established CD and ileocecal resection due to the disease. IUS (HI-VISION Avius®, Tokyo, Japan) was performed with linear probe B-mode/Doppler prior to ileocolonoscopy. IUS and ileocolonoscopy were performed on the same day by 2 specialists in Gastroenterology dedicated to ultrasound and inflammatory bowel disease, in a double-blind mode. Collected demographic and clinical data (Harvey-Bradshaw Index [HBI]; remission ≤4), serological/fecal inflammatory parameters (leukocytes [4–10 × 10⁹ cells/L], C-reactive protein [≤0.5 mg/dL], and fecal calprotectin [&#x3c;50 mg/kg]), endoscopy (Rutgeerts score: remission &#x3c;i2), and ultrasound (intestinal wall thickening [≤3 mm] and digestive wall vascularization using the semiquantitative score of Limberg [absent = 0, sparse = 1, moderate = 2, and marked = 3]). <b><i>Results:</i></b> Thirty-nine patients (female: 64.1%, mean age: 43.5 ± 15.3 years) were included. The median post-surgery follow-up was 9 years (IQR 3–12). The Montreal classification was as follows: L1, 61.5% (<i>n</i> = 24); L3, 38.5% (<i>n</i> = 15); B1 and B2, 28.2% (<i>n</i> = 11); and B3, 43.6% (<i>n</i> = 17). Most patients were in clinical remission (87.2%; <i>n</i> = 34), with a mean HBI of 2.1 ± 2.2. Twenty-two patients (56.4%) had normal inflammatory markers. IUS (intestinal wall thickening &#x3e;3 mm and/or Limberg score &#x3e;1) was abnormal in 61.5% (<i>n</i> = 24) of the cases. Endoscopic remission (Rutgeerts score &#x3c;i2) in 53.8% (<i>n</i> = 21) of the cases. Compared to endoscopy, IUS (area under the receiver operating characteristic curve [AUROC] = 0.75, <i>p</i> = 0.007) showed a diagnostic accuracy superior to that of inflammatory parameters (AUROC = 0.66, <i>p</i> = 0.083) and clinical parameters (AUROC = 0.64, <i>p</i> = 0.139). IUS showed a moderate concordance with endoscopy (κ = 0.5, <i>p</i> = 0.001), which was higher than that with inflammatory parameters (ĸ = 0.33, <i>p</i> = 0.041) or clinical parameters (ĸ = 0.29, <i>p</i> = 0.01). <b><i>Conclusions:</i></b> Ultrasound evaluation of the digestive wall is a noninvasive technique that shows a good diagnostic accuracy and a moderate concordance with endoscopy, being superior to clinical and serological/fecal inflammatory parameters.

Endoscopic Prediction of Crohn’s Disease Postoperative Recurrence

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

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

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

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

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

Το εύρος κατανομής του μεγέθους των ερυθρών αιμοσφαιρίων με συντελεστή μεταβλητότητας ως δείκτης ενεργότητας και βαρύτητας στα ιδιοπαθή φλεγμονώδη νοσήματα του εντέρου

ΣΚΟΠΟΣ: Η φυσική ιστορία των ΙΦΝΕ περιλαμβάνει περιόδους υφέσεων και εξάρσεων κατά τις οποίες παρατηρείται σημαντική ελάττωση στην ποιότητα ζωής των ασθενών και αυξημένος κίνδυνος νοσηλείας, επιπλοκών και χειρουργικών επεμβάσεων. Η επιτήρηση των ασθενών αποσκοπεί στην έγκαιρη αναγνώριση και πρόληψη της υποτροπής τροποποιώντας ή/και κλιμακώνοντας πρώιμα την φαρμακευτική αγωγή. Η παρακολούθηση των ασθενών βασίζεται στη χρήση κλινικών, εργαστηριακών, ενδοσκοπικών, ιστολογικών και απεικονιστικών παραμέτρων οι οποίες, παρουσιάζουν επιμέρους μειονεκτήματα κατά την εφαρμογή τους, όπως όπως χαμηλή ευαισθησία, υψηλό κόστος, περιορισμένη προσβασιμότητα και επεμβατικότητα.. Το RDW-CV αποτελεί ένα εύχρηστο οικονομικό δείκτη ο οποίος υπολογίζεται αυτόματα από τους αιματολογικούς αναλυτές και έχει διαπιστωθεί ότι μπορεί να εκφράσει με επιτυχία την ενεργότητα και τη βαρύτητα σε πλήθος παθολογικών καταστάσεων. Περιορισμένα είναι τα δεδομένα στη διεθνή βιβλιογραφία αναφορικά με τη χρήση του ως δείκτη φλεγμονής στα ΙΦΝΕ. Πρωτεύων σκοπός της παρούσας μελέτης είναι η διερεύνηση της ακρίβειας του RDW-CV στη διάγνωση της ενδοσκοπικής και ιστολογικής ενεργότητας και βαρύτητας σε ασθενείς με ΙΦΝΕ. Ακολούθως διερευνήθηκε η επίδραση της αναιμίας στη διαγνωστική του ακρίβεια, συγκρίθηκε η διαγνωστική του ακρίβεια με της CRP και της ΤΚΕ και αξιολογήθηκε η συσχέτιση του με κλινικούς, εργαστηριακούς, ενδοσκοπικούς και ιστολογικούς δείκτες ενεργότητας στα ΙΦΝΕ. ΥΛΙΚΟ ΚΑΙ ΜΕΘΟΔΟΙ: Πρόκειτα για μια μελέτη χρονικής στιγμής στην οποία συμπεριλήφθηκαν 131 ασθενείς με τεκμηριωμένη διάγνωση ΙΦΝΕ, εκ των οποίων 75 ασθενείς με NC με μέση ηλικία 38,49 ± 14,5 έτη και διάμεση διάρκεια νόσου 4,91 (0-34,91) έτη και 56 ασθενείς με ΕΚ με μέση ηλικία 41,96 ±15,85 έτη και διάμεση διάρκεια νόσου 6,75 (0,08-34,83) έτη. Στους ασθενείς υπολογίστηκαν οι ακόλουθες παράμετροι: CDAI, partial Mayo score, γενική αίματος, CRP, TKE, φεριτίνη, σίδηρος, φυλλικό οξύ, Β12, SES-CD, endoscopic Mayo score, Rutgeerts score, GHAS και Nancy index. ΑΠΟΤΕΛΕΣΜΑΤΑ: Διαπιστώθηκε αξιοσημείωτη διαγνωστική ακρίβεια του RDW-CV στην ενδοσκοπική ενεργότητα στο σύνολο των ασθενών, με σχετική υπεροχή στους ασθενείς με ΝC. Παρατηρήθηκε σημαντική διαγνωστική ακρίβεια στην ενδοσκοπική μετεγχειρητική υποτροπή σε ασθενείς με ΝC, και υπεροχή της ακρίβειας του στη διάγνωση της ενδοσκοπικής ενεργότητα στους ασθενείς με ΝC με αναιμία. Η ακρίβεια του στη διάγνωση της ενδοσκοπικής βαρύτητας ήταν ικανοποιητική και στις δύο ομάδες ασθενών, ενώ η διαγνωστική ακρίβεια του RDW-CV ήταν συγκρίσιμη με της CRP και της TKE σε όλες τις περιπτώσεις. Διαπιστώθηκε ικανοποιητική διαγνωστική ακρίβεια του RDW-CV στην ιστολογική ενεργότητα στο σύνολο των ασθενών, με σχετική υπεροχή της ικανότητας του στους ασθενείς με NC. H ακρίβεια του στη διάγνωση της ιστολογικής ενεργότητα υπερείχε στους ασθενείς με ΝC με αναιμία, ενώ σημαντικότατη ήταν η διαγνωστική ακρίβεια του στη βαρεία νόσο και στις δύο ομάδες ασθενών. Η διαγνωστική του ακρίβεια του RDW-CV ήταν συγκρίσιμη με της CRP της TKE σε όλες τις υποαναλύσεις. Τέλος παρατηρήθηκε σημαντική συσχέτιση του με κλινικούς, εργαστηριακούς ενδοσκοπικούς και ιστολογικούς και δείκτες ενεργότητας. ΣΥΜΠΕΡΑΣΜΑ: Tο RDW-CV αποτελεί ένα εύχρηστο, οικονομικό δείκτη με αξιοσημείωτη ακρίβεια στη διάγνωση της ενδοσκοπικής και ιστολογικής ενεργότητας και βαρύτητας στα ΙΦΝΕ, συγκρίσιμη με ευρέως χρησιμοποιούμενους βιοδείκτες. Επιπρόσθετα το RDW-CV σχετίζεται σημαντικά με εργαστηριακούς, κλινικούς, ενδοσκοπικούς και ιστολογικούς δείκτες, ικανούς να εκφράσουν την ενεργότητα, τόσο στη NC όσο και στην ΕΚ.

OP18 Surgical prevention of anastomotic recurrence by excluding mesentery in Crohn’s disease: The SuPREMe-CD study

Background Recently, a new antimesenteric, functional end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence score and surgical recurrence rate in Crohn’s disease (CD).This trial aimed to provide randomised controlled data comparing Kono-S anastomosis and stapled ileocolic side-to-side anastomosis. Methods Randomised controlled trial at a tertiary referral institution, enrolling and randomising to undergo either the ‘Kono group’ or the ‘Conventional group’, all CD subjects needing surgery. Primary endpoint: endoscopic recurrence (ER) (Rutgeerts score ≥i2) after 6 months. Secondary endpoints: clinical recurrence (CR) after 12 and 24 months, ER after 18 months and surgical recurrence (SR) after 24 months. Also, short-term outcomes and postoperative complications were recorded. A sample size of 70 patients (35 in each group) was considered necessary to demonstrate a reduction &gt;30% in endoscopic recurrence at 6 months follow-up in the Kono group when assuming a 60% endoscopic recurrence expected rate in the control group. Results 79 CD patients were enrolled and randomised in the Kono group (36) or Conventional group (43) (Table 1). After 6 months, 22.2% in the Kono group and 62.8% in the Conventional group presented an ER (p &lt; 0.001; OR 5.91). A severe postoperative ER (Rutgeerts score ≥i3) was found in 13.8% of Kono vs. 34.8% of Conventional group (p = 0.03; OR 3.32). CR rate was 8% in the Kono group vs. 18% in the Conventional group after 12 months (p = 0.2) and 18% vs. 30.2% after 24 months (p = 0.04, OR 3.47). SR rate after 24 months was 0% in the Kono group vs. 4.6% in the Conventional group (p = 0.3). Patients with Kono-S anastomosis presented a longer time until CR than patients with side-to-side anastomosis (HR 0.36, p = 0.037). On binary logistic regression analysis, the Kono-S anastomosis was the only variable significantly associated with a reduced risk of ER (OR 0.19, p &lt; 0.001). About postoperative outcomes, there were no differences between Kono and Conventional groups in terms of surgery duration (p = 0.8), days to gas (p = 0.4) or stool canalisation (p = 0.8) and postoperative stay (p = 0.3). Infections (included wound infection) were found in 4 subjects in the Kono group (13.7%) vs. 6 patients (16.6%) in the Conventional group (p = 0.749). Conclusion This is the first RCT comparing Kono-S anastomosis vs. standard anastomosis in CD, which found a significant reduction of postoperative endoscopic recurrence rate by using the novel technique, without concerns about safety. The Kono-S anastomosis could be considered the new recommended surgical technique in CD. ClinicalTrial.gov NCT02631967.

P462 Efficacy of ustekinumab for the prevention of postoperative recurrence in crohn’s disease. Data from clinical practice from the eneida registry

Background Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases these drugs are contraindicated or have previously failed. Recently, ustekinumab was licensed for CD but no data on its efficacy in the prevention of POR is still available. Methods All CD patients in whom ustekinumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a prospectively maintained database of the Spanish Working Group in IBD –GETECCU-). We evaluated the rates of endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score &gt;i1 and advanced endoscopic POR by &gt;i2. Results Thirty patients were included; ustekinumab was started after a median time of 60 days (IIQ 31–90). Concomitant immunosuppressants were used in 17%, 27% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 23% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. In total, 36% of them had more than one risk factor. 50% had been exposed to ustekinumab prior to the index surgery (46% within the last 6 months). The median time of follow-up on ustekinumab was 17 months (IQR 11–21). Fifty-six per cent of patients had at least one endoscopic assessment within 18 months after surgery: 58% had endoscopic POR and 23% advanced endoscopic POR. Additionally, 13% presented clinical POR at the discretion of the treating physician and none developed surgical POR. Conclusion In a small clinical practice cohort, ustekinumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR. Unfortunately, the lack of early endoscopic monitoring is still frequent despite the recommendations from guidelines.

P681 Efficacy of vedolizumab for the prevention of postoperative recurrence in Crohn’s disease: Data from clinical practice from the ENEIDA registry

Background Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases, these drugs are contraindicated or have previously failed. Vedolizumab was licensed for CD some years ago but scarce data on its efficacy for the prevention of POR is available. Methods All CD patients in whom vedolizumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD, GETECCU). We evaluated the rates of Endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score &gt;i1 and advanced endoscopic POR by &gt;i2. Results Twenty-three patients were included; vedolizumab was started after a median time of 23 days (IIQ21-73). Concomitant immunosuppressants were used in 17%; 18% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 13% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. Thirty-four per cent had been exposed to vedolizumab prior to the index surgery (26% within the last 6 months). The median time of follow-up on ustekinumab was 26 months (IQR 11–31). Eighty-three per cent of patients had at least one endoscopic assessment within 18 months after surgery: 40 % had endoscopic POR and 15% advanced endoscopic POR. Additionally, 22% presented clinical POR at the discretion of the treating physician and 9% developed surgical POR. Conclusion In a small clinical practice cohort, vedolizumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR.