Felix Goutorbe

Diffusion-Weighted Magnetic Resonance Imaging in Ileocolonic Crohn's Disease: Validation of Quantitative Index of Activity

OBJECTIVES:Magnetic resonance imaging (MRI) allows accurate assessment of Crohns disease (CD), but requires gadolinium injection. Diffusion-weighted (DW)-MRI yields comparable performances in small bowel CD. We compared the accuracy of DW-MR enterocolonography (MREC) and the magnetic resonance index of activity (MaRIA), and performed an external validation of the Clermont score in assessing inflammation in CD.METHODS:This was an observational prospective study of a single-center cohort. A total of 130 CD patients underwent consecutively MREC with gadolinium injection and DWI sequences between July 2011 and December 2012.RESULTS:Of the 848 evaluated segments (small bowel=352, colon/rectum=496), 175 (20.6%) were active (small bowel=111, colon/rectum=64) defined as MaRIA ≥7. Using a receiver operating characteristic (ROC) curve, we determined an apparent coefficient of diffusion (ADC) threshold of 1.9 × 10−3 mm2/s that yielded a sensitivity and a specificity in discriminating active from nonactive CD of 96.9% and 98.1%, respectively, for the colon/rectum, and 85.9% and 81.6%, respectively, for the ileum. ADC was better correlated to MaRIA ≥7 than related contrast enhancement obtained with injected sequences (P<0.001). The Clermont score (=1.646 × bowel thickness−1.321 × ADC+5.613 × edema+8.306 × ulceration+5.039) was highly correlated with the MaRIA (rho=0.99) in ileal CD but not in colonic CD (rho <0.80). Interobserver agreement was high with regard to ADC measurement (correlation >0.9, P<0.001, and concordance >0.9, P<0001).CONCLUSIONS:DW-MREC is a reliable tool to assess inflammation in colonic (ADC) and ileal (Clermont score) CD and its use in daily practice would avoid gadolinium injection.

Diffusion-weighted magnetic resonance enterocolonography in predicting remission after anti-TNF induction therapy in Crohn's disease.

BACKGROUND Diffusion-weighted magnetic resonance entero-colonography (DW-MREC) with no rectal distension and with no bowel cleansing is accurate to assess inflammatory activity in ileocolonic Crohns disease (CD). AIM To study DW-MREC parameters as predictors of remission (CDAI < 150 and CRP < 5mg/L) after anti-TNF induction therapy. METHODS Forty consecutive CD patients were prospectively and consecutively included. All the patients underwent DW-MREC with apparent diffusion coefficient (ADC) and MaRIA calculation before starting anti-TNF. Mean ADC was defined as the mean of the segmental ADC. RESULTS Twenty patients (50.0%) experienced remission at W12. Low mean ADC (2.05 ± 0.22 vs 1.89 ± 0.25, p = 0.03) and high total MaRIA (39.2 ± 16.6 vs 51.7 ± 18.2, p = 0.03) were predictive of remission at W12. Using a ROC curve, we determined a mean ADC of 1.96 as predictive cut-off of remission at W12 (AUC = 0.703 [0.535-0.872]) with sensitivity, specificity, positive predictive value and negative predictive value of 70.0%, 65.0%, 66.7% and 68.4%, respectively. In multivariate analysis, mean ADC < 1.96 (OR = 4.87, 95% CI [1.04-22.64]) and total MaRIA > 42.5 (OR = 5.11, 95% CI [1.03-25.37]), reflecting high inflammatory activity, were predictive of remission at week 12. CONCLUSIONS DW-MREC using quantitative parameters i.e. ADC, is useful in detecting and assessing inflammatory activity but also to predict efficacy of anti-TNF induction therapy in CD.

Faecal chitinase 3-like 1 is a reliable marker as accurate as faecal calprotectin in detecting endoscopic activity in adult patients with inflammatory bowel diseases

Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs).

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease.

AIM To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. METHODS From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohns disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006). CONCLUSION Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease

BACKGROUND As surgical resection is not curative in Crohns disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. AIMS To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohns disease. METHODS From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohns disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. RESULTS Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6-48.6], p=0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4-11.2], p=0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. CONCLUSION Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohns disease.

Fecal Matrix Metalloprotease-9 and Lipocalin-2 as Biomarkers in Detecting Endoscopic Activity in Patients With Inflammatory Bowel Diseases

Background: Fecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBD). Goals: We aimed to evaluate the accuracy of fecal matrix metalloprotease-9 (MMP-9) and fecal lipocalin-2 (LCN-2) compared with calprotectin in detecting endoscopic activity in IBD Study: Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn’s disease Endoscopic Index of Severity (CDEIS) in Crohn’s disease (CD) patients or Mayo endoscopic subscore calculation for ulcerative colitis (UC) patients, and stool collection. Fecal calprotectin was measured using quantitative immunochromatographic testing. Fecal MMP-9 and LCN-2 was quantified by enzyme-linked immunosorbent assay. MMP-9 and LCN-2 thresholds were determined using receiver operating curves. Results: In 54 CD patients, fecal calprotectin, MMP-9 and LCN-2 correlated with CDEIS and were significantly increased in patients with endoscopic ulcerations. MMP-9 >350 ng/g detected endoscopic ulceration in CD with a sensitivity of 90.0% and a specificity of 63.6%, compared with fecal calprotectin >250 &mgr;g/g (sensitivity=90.5% and specificity=59.1%). Fecal LCN-2 demonstrated lower performances than the 2 other biomarkers (sensitivity=85.7% and specificity=45.5%). In 32 UC patients, fecal MMP-9, LCN-2, and calprotectin levels were significantly increased in patients with endoscopic activity. In UC patients, fecal MMP-9 >900 ng/g had the best efficacy to detect endoscopic activity (sensitivity=91.0% and specificity=80.0%, compared with fecal calprotectin >250 &mgr;g/g (sensitivity=86.4% and specificity=80.0%) and LCN-2 >6700 ng/g (sensitivity=82.0% and specificity=80.0%). Conclusions: Fecal MMP-9 is a reliable biomarker in detecting endoscopic activity in both UC and CD patients.

Faecal calprotectin and magnetic resonance imaging in detecting Crohn’s disease endoscopic postoperative recurrence

AIM To assess magnetic resonance imaging (MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn’s disease (CD). METHODS From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo (5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level. Endoscopic postoperative recurrence (POR) was defined as Rutgeerts’ index ≥ i2b. The MRI was analyzed independently by two radiologists blinded from clinical data. RESULTS Apparent diffusion coefficient (ADC) was lower in patients with endoscopic POR compared to those with no recurrence (2.03 ± 0.32 vs 2.27 ± 0.38 × 10-3 mm²/s, P = 0.032). Clermont score (10.4 ± 5.8 vs 7.4 ± 4.5, P = 0.038) and relative contrast enhancement (RCE) (129.4% ± 62.8% vs 76.4% ± 32.6%, P = 0.007) were significantly associated with endoscopic POR contrary to the magnetic resonance index of activity (MaRIA) (7.3 ± 4.5 vs 4.8 ± 3.7; P = 0.15) and MR scoring system (P = 0.056). ADC < 2.35 × 10-3 mm²/s [sensitivity = 0.85, specificity = 0.65, positive predictive value (PPV) = 0.85, negative predictive value (NPV) = 0.65] and RCE > 100% (sensitivity = 0.75, specificity = 0.81, PPV = 0.75, NPV = 0.81) were the best cut-off values to identify endoscopic POR. Clermont score > 6.4 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74), MaRIA > 3.76 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74) and a MR scoring system ≥ MR1 (sensitivity = 0.54, specificity = 0.82, PPV = 0.70, and NPV = 0.70) demonstrated interesting performances to detect endoscopic POR. Faecal calprotectin values were significantly higher in patients with endoscopic POR (114 ± 54.5 μg/g vs 354.8 ± 432.5 μg/g; P = 0.0075). Faecal calprotectin > 100 μg/g demonstrated high performances to detect endoscopic POR (sensitivity = 0.67, specificity = 0.93, PPV = 0.89 and NPV = 0.77). CONCLUSION Faecal calprotectin and MRI are two reliable tools to detect endoscopic POR in patients with CD.

Effectiveness and safety of anti-TNF therapy for inflammatory bowel disease in liver transplant recipients for primary sclerosing cholangitis: A nationwide case series

BACKGROUND There is a lack of consensus regarding the treatment of inflammatory bowel disease (IBD) after liver transplantation (LT) forprimary sclerosing cholangitis (PSC). AIM To investigate the safety and effectiveness of anti-TNF therapy in patients with IBD after a LT for PSC. METHODS We reviewed the medical files of all of the IBD patients who underwent a LT for PSC and who were treated with anti-TNF therapy at 23 French liver transplantation centers between 1989 and 2012. RESULTS Eighteen patients (12 with ulcerative colitis and 6 who had Crohns disease) were recruited at 9 LT centers. All of these patients received infliximab or adalimumab following their LT, and the median duration of their anti-TNF treatment was 10.4 months. The most frequent concomitant immunosuppressive treatment comprised a combination of tacrolimus and corticosteroids. Following anti-TNF therapy induction, a clinical response was seen in 16/18 patients (89%) and clinical remission in 10 (56%). At the end of the anti-TNF treatment or at the last follow-up examination (the median follow-up was 20.9 months), a clinical response was achieved in 12 patients (67%) and clinical remission in 7 (39%). A significant endoscopic improvement was observed in 9 out of 14 patients and a complete mucosal healing in 3 out of 14 patients (21%). Six patients experienced a severe infection. These were due to cholangitis, cytomegalovirus (CMV) infection, Clostridium difficile, cryptosporidiosis, or Enterococcus faecalis. Three patients developed colorectal cancer after LT, and two patients died during the follow-up period. CONCLUSIONS Anti-TNF therapy proved to be effective for treating IBD after LT for PSC. However, as 17% of the patients developed colorectal cancer during the follow-up, colonoscopic annual surveillance is recommended after LT, as specified in the current guidelines.

Sa1895 Myenteric Plexitis Is a Risk Factor for Endoscopic and Clinical Postoperative Recurrence After Ileocolonic Resection in Crohn's Disease

a b s t r a c t Background: As surgical resection is not curative in Crohns disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. Aims: To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohns disease. Methods: From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohns disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. Results: Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In mul- tivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% (1.6-48.6), p = 0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% (1.4-11.2), p = 0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. Conclusion: Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohns disease.

Su1228 Diffusion-Weighted Magnetic Resonance Enterocolonography Before Treatment Predicts Remission After Anti-TNF Therapy in Crohn's Disease

Background: In the era of biologics, mucosal healing became a therapeutic target in Crohns disease (CD) patients, however, this outcome is difficult to evaluate in daily practice because it induce the need of repeated colonoscopies. Diffusion-weighted magnetic resonance enterocolonography (DW-MREC) has shown good accuracy to detect and assess inflammatory activity in CD [1] [2]. We aimed to assess the correlation between endoscopic lesions and DW-MREC parameters i.e. Apparent Diffusion Coefficient (ADC) and Clermont score (CS) [2].Methods: In this prospective study, all the patients underwent consecutively DW-MREC with no bowel cleansing, with no rectal enema [2] and colonoscopy within 4 weeks (mean interval=17±11 days). Radiologists were blinded from endoscopic findings and endoscopists were blinded from radiologic findings. Results are given in mean ± standard deviation. Results: Among the 43 CD patients, 9 (20.5%) had previous intestinal surgery. CDAI, CRP and fecal calprotectin value were 179±93, 31.1±8.0g/L and 1172.9±730.3μg/g, respectively. The CDEIS, SES-CD and CS were 6.8±7.1, 9.2+/-8.0 and 15.8±10.7, respectively. Mean ADC was inversely correlated with CDEIS (rho=-0.40; p=0.0067) and SES-CD (rho=-0.33; p=0.032). Considering the 194 segments (ileum=37, colorectal=159), ADC was inversely correlated with segmental CDEIS (-0.48; p 20mm (1.50±0.53)(p=0.0001). Considering the 37 ileal segments, CS correlated with ileal CDEIS (0.62; p 18.9 detected ulcerations with Se=0.79 and Spe=0.73. CS increased with the ulceration size (p=0.012). Conclusions: Although MRI correlated moderately with endoscopic scores, DW-MREC using ADC and Clermont score was highly effective to indirectly detect endoscopic ulcerations in CD. Thus, DW-MREC could lead to define MRI healing as a new treatment goal in CD, and could be easily used both in daily practice and in clinical trials. [1] Buisson A et al. Aliment Pharmacol ther 2013;37:537-45. [2] Hordonneau C et al. Am J Gastroenterol 2014;109:89-98.