Faster and less invasive tools to identify patients with ileal colonization by adherent-invasive E. coli in Crohn's disease.

BACKGROUND AND AIMS: The identification of Crohn's disease (CD)-associated adherent and invasive Escherichia coli (AIEC) is time-consuming and requires ileal biopsies. We aimed to identify a faster and less invasive methods to detect ileal colonization by AIEC in CD patients. METHODS: CD patients requiring ileo-colonoscopy were consecutively enrolled in this prospective multicenter study. Samples from saliva, serum, stools, and ileal biopsies of CD patients were collected. RESULTS: Among 102 CD patients, the prevalence of AIEC on ileal biopsies was 24.5%. The abundance and global invasive ability of ileal-associated total E. coli were respectively ten-fold (p = 0.0065) and two-fold (p = 0.0007) higher in AIEC-positive (vs. AIEC-negative), while abundance of total E. coli in the feces was not correlated with AIEC status in the ileum. The best threshold of ileal total E. coli was 60 cfu/biopsy to detect AIEC-positive patients, with high negative predictive value (NPV) (94.1%[80.3-99.3]), while the global invasive ability (>9000 internalized bacteria) was able to detect the presence of AIEC with high positive predictive value (80.0% [55.2-100.0]). Overall, 78.1% of the AIEC + patients were colonized by two or less different AIEC strains. The level of serum anti-total E. coli antibodies (AEcAb) was higher in AIEC-positive patients (p = 0.038) with a very high negative predictive value (96.6% [89.9-100.0]) (p = 0.038) for a cut-off value > 1.9 × 10-3 . CONCLUSIONS: More than two thirds of AIEC-positive CD patients were colonized by two or less AIEC strains. While stools samples are not accurate to screen AIEC status, the AEcAb level appears to be an attractive, rapid and easier biomarker to identify patients with Crohn's disease harboring AIEC.

Oral Curcumin No More Effective Than Placebo in Preventing Recurrence of Crohn's Disease After Surgery in a Randomized Controlled Trial.

BACKGROUND AND AIMS: Recurrence of Crohn's disease (CD) after surgery is a major concern. Curcumin has anti-inflammatory properties and induces endoscopic remission in patients with ulcerative colitis. We investigated the efficacy of curcumin vs placebo in preventing post-operative recurrence of CD, based on endoscopic and clinical indices, in patients receiving concomitant thiopurine therapy. METHODS: We conducted a double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, of 62 consecutive patients with CD undergoing bowel resection. Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy. We also collected data on CD activity index, results from laboratory tests, and answers to quality of life questionnaires during this 6-month period. The primary endpoint was postoperative recurrence of CD in each group (Rutgeerts' index score ≥i2) at month 6 (determined by central reading). An interim analysis (intent to treat) was scheduled after 50% of the patients were enrolled. RESULTS: At month 6, postoperative recurrence (Rutgeerts' index score ≥i2) occurred in 18 patients (58%) receiving curcumin and 21 patients (68%) receiving placebo (P = .60). A significantly higher proportion of patients receiving curcumin (55%) had a severe recurrence of CD (Rutgeerts' index score ≥i3) than patients receiving placebo (26%) (P = .034). We observed a clinical recurrence of CD (CD activity index score >150) at month 6 in 45% of patients receiving placebo and 30% of patients receiving curcumin (P = .80). Quality of life scores at month 6 did not differ significantly between groups (P = .80). Severe adverse events developed in 6% of patients receiving placebo and 16% of patients receiving curcumin (P = .42). CONCLUSIONS: In a randomized controlled trial of patients who underwent surgery for CD and received thiopurine treatment, we found that curcumin was no more effective than placebo in preventing CD recurrence. There were no significant differences between groups in quality of life or severe adverse events. The study was discontinued after interim analysis due to futility. ClinicalTrials.gov no: NCT 02255370.

Macrophages Inability to Mediate Adherent-Invasive E. coli Replication is Linked to Autophagy in Crohn's Disease Patients.

The macrophages from Crohn's Disease (CD) patients are defective to control the replication of CD-associated adherent-invasive E. coli (AIEC). We aimed to identify the host factors associated with AIEC replication focusing on polymorphisms related to autophagy. Peripheral blood monocyte-derived macrophages (MDM), obtained from 95 CD patient, 30 ulcerative colitis (UC) patients and 15 healthy subjects, were genotyped for several CD-associated polymorphisms. AIEC bacteria survival increased within MDM from CD patients compared to UC (p = 0.0019). AIEC bacteria survival increased in patients with CD-associated polymorphism IRGM (p = 0.05) and reduced in those with CD-associated polymorphisms XBP-1 (p = 0.026) and ULK-1 (p = 0.033). AIEC infection led to an increase of pro-inflammatory cytokines IL-1ß (p < 0.0001) and TNF-α (p < 0.0001) in CD macrophages. ULK-1 expression increased in AIEC-infected MDM from CD patients compared to MDM from UC patients or healthy subjects (p = 0.0056) and correlated with AIEC survival (p = 0.0013). Moreover, the expression of ULK-1 phosphorylation on Serine 757 decreased following to AIEC infection (p < 0.0001). Short-term silencing of ULK-1 and IRGM genes restricted and promote, respectively, AIEC survival within MDM (p = 0.0018 and p = 0.0291). In conclusion, the macrophage defect to mediate AIEC clearance in CD patients is linked to polymorphisms related to autophagy such as IRGM and ULK-1.

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease.

BACKGROUND: The individual performances and the complementarity of Crohn's disease (CD) activity index (CDAI), C-reactive protein (CRP) and faecal calprotectin (Fcal) to monitor patients with CD remain poorly investigated in the era of "tight control" and "treat to target" strategies. AIM: To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk (W12) of anti-tumor necrosis factor (TNF) therapy to predict corticosteroids-free remission (CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 µg/g with no therapeutic intensification and no surgery) at W52. METHODS: CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP > 2.9 mg/L or Fcal > 250 µg/g were prospectively enrolled. RESULTS: Among the 40 included patients, 13 patients (32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12 (P = 0.012), CRP level < 2.9 mg/L at W12 (P = 0.001) and Fcal improvement at W12 (Fcal < 300 µg/g; or, for patients with initial Fcal < 300 µg/g, at least 50% decrease of Fcal or normalization of Fcal (< 100 µg/g) (P = 0.001) were predictive of CFREM at W52. Combined endpoint (CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0% (100.0-100.0) and negative predictive value = 87.1% (75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio (OR) = 45.1 (2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3 (0.36-237.1); P = 0.145] and CRP < 2.9 mg/L (0.77-278.0; P = 0.073). CONCLUSION: The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

Bowel wall healing assessed using magnetic resonance imaging predicts sustained clinical remission and decreased risk of surgery in Crohn's disease.

BACKGROUND: Endoscopic mucosal healing is considered as the best therapeutic target in Crohn's disease (CD) as it is associated with better long-term outcomes. We investigated whether bowel wall healing (BWH) assessed using magnetic resonance imaging (MRI) could predict favorable outcomes and could be a potential therapeutic target. METHODS: We performed a post hoc analysis from two prospective studies (n = 174 patients). All the patients with previous objective signs of bowel inflammation and assessed by MRI for therapeutic efficacy had a standardized and blinded evaluation, and underwent MRI. Complete BWH was defined as no segmental MaRIA > 7 or no segmental Clermont score > 8.4 and BWH as no segmental MaRIA > 11 or no segmental Clermont score > 12.5. Clinical corticosteroid-free remission (CFREM) was defined as no reappearance or worsening of clinical manifestation leading to therapeutic modification, hospitalization or CD-related surgery. Multivariate analyses were performed including all the relevant parameters. RESULTS: Overall, 63 patients with CD were included (mean follow-up = 4.8 ± 3.1 semesters). In multivariate analysis (n = 303 semesters), complete BWH or BWH was associated with sustained CFREM according to MaRIA [OR = 4.42 (2.29-26.54); p = 0.042 and OR = 3.43 (1.02-27.02); p = 0.047, respectively] or Clermont score [OR = 3.09 (1.01-12.91); p = 0.049 and OR = 3.88 (1.40-13.80); p = 0.036, respectively]. In multivariate analysis (n = 63 patients), complete BWH or BWH was associated with decreased risk of surgery using MaRIA [HR = 0.16 (0.043-0.63); p = 0.008 and HR = 0.24 (0.07-0.77); p = 0.017, respectively] or Clermont score [HR = 0.24 (0.07-0.78); p = 0.016 and HR = 0.23 (0.07-0.76); p = 0.016, respectively]. CONCLUSIONS: MRI endpoints are predictive of favorable outcomes after medical therapy and could be used as therapeutic target in daily practice and clinical trials.

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.

Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn's Disease-Like Complications of the Pouch After Ileal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Colitis.

Background: Inflammatory complications including chronic refractory pouchitis and Crohn's disease (CD)-like complications of the pouch are common complications after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC). We performed a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in distinguishing patients with chronic refractory pouchitis from those with CD-like complications of the pouch. Methods: We performed a systematic literature search to identify articles and abstracts reporting anti-TNF agents efficacy in treating inflammatory complications of the pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8 weeks 95%CI[5-10] and 12 months 95%CI[12-18.5], respectively. Results: We identified 21 articles and 3 abstracts including 313 patients treated either with infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of the pouch. The rates of short-term and long-term clinical remission were 0.50 (95%CI [0.37-0.63]; I2 = 0.57) and 0.52 (95%CI[0.39-0.65]; I2 = 0.59), respectively. The rate of remission after anti-TNF induction therapy seemed to be higher in CD-like complications of the pouch 0.64 (95%CI[0.5-0.77]; I2 = 0.18), compared to refractory pouchitis 0.10 (95%CI [0.00-0.35]; I2 = 0.00) (P = 0.06), whereas no such difference appeared after long-term maintenance therapy 0.57 (95%CI[0.43-0.71]; I2 = 0.32) and 0.37 (95%CI [0.14-0.62]; I2 = 0.47), respectively (P = 0.57). Sensitivity analyses suggested no difference in outcomes. No significant publication bias has been detected. Conclusion: Anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities both in daily practice and clinical trials.

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 µg/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 µg/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.

Magnetic resonance index of activity (MaRIA) and Clermont score are highly and equally effective MRI indices in detecting mucosal healing in Crohn's disease.

BACKGROUND: Magnetic resonance index of activity (MaRIA) and Clermont score are currently the two main MRI indices that have been validated compared to endoscopy in Crohn's disease (CD). AIMS: To compare the accuracy of MaRIA and Clermont score in assessing CD mucosal healing. METHODS: Fourty-four CD patients underwent prospectively and consecutively MRI and colonoscopy. RESULTS: Considering 207 segments, MaRIA>7 and Clermont score>8.4 demonstrated substantial accuracy to detect endoscopic ulcerations (73.9% and 74.0%, respectively) and presented with high specificity (82.1% and 81.3%) and high negative predictive value (NPV) (82.1% and 82.4%) for MaRIA and Clermont score, respectively. The sensitivity for detecting deep ulcerations was 90.9% for both MaRIA>11 and Clermont score>12.5, with a specificity of 82.0% and 80.0%, respectively. Among 44 patients, deep MRI remission predicted mucosal healing with specificity=85.3% and NPV=85.3% according to Barcelona criteria (no segmental MaRIA>7), and specificity=88.2% and NPV=85.7% according to Clermont criteria (no segmental Clermont score>8.4). In addition, MRI remission predicted mucosal healing with specificity=76.5% and NPV=86.7% according to Barcelona criteria (no segmental MaRIA>11), and specificity=79.4% and NPV=84.4% according to Clermont criteria (no segmental Clermont score>12.5). CONCLUSION: MaRIA and Clermont score are equally effective in detecting CD endoscopic ulcerations supporting their use as therapeutic endpoints.

Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional Imaging Predictors of Therapeutic Failure.

BACKGROUND: Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. AIM: To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. METHODS: In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Among 84 patients, therapeutic failure rate within 60 months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37-11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p = 0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p = 0.047) were associated with short-term clinical failure. CONCLUSION: Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.

Temporary placement of a covered duodenal stent can avoid riskier anterograde biliary drainage when ERCP for obstructive jaundice fails due to duodenal invasion.

BACKGROUND: Duodenal stenosis is one of the most common causes of failed ERCP for obstructive jaundice. Alternative approaches include anterograde biliary drainage, with higher morbidity. We report in this study the efficacy and safety of temporary placement of a covered duodenal self-expandable metal stent (cSEMS) in order to access the papilla and achieve secondary retrograde biliary drainage in patients with obstructive jaundice and failed ERCP due to concomitant duodenal stenosis. METHODS: From June 2006 to March 2014, a total of 26 consecutive patients presenting obstructive jaundice without severe sepsis with failed ERCP due to duodenal invasion were enrolled. A temporary 7-day duodenal cSEMS was placed during the failed ERCP, and a second ERCP was attempted at day 7 after duodenal stent removal. RESULTS: Duodenal cSEMS placement and retrieval were technically successful in all cases. Access to the papilla at day 7 was possible in 25 cases (96 %, 95 % CI 80-99 %). Secondary successful ERCP was achieved in 19 cases (76 %, 95 % CI 55-91 %, i.e., 73 %, 95 % CI 73-86 %, in an intention-to-treat analysis). Mean bilirubin level was 102 ± 90 µmol/L at baseline rising to 164 ± 121 µmol/L at day 7. There were 6 stent migrations and no adverse events recorded between the two ERCPs. CONCLUSIONS: When ERCP for obstructive jaundice fails due to duodenal invasion, temporary cSEMS placement offers a safe and effective way to achieve successful secondary ERCP while avoiding riskier endoscopic ultrasound or percutaneous transhepatic anterograde biliary drainage.

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 Crohn's 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.

The Clinical Outcome in Patients Treated With a Newly Designed SEMS in Cervical Esophageal Strictures and Fistulas.

BACKGROUND AND GOALS: Using a self-expandable metallic stent (SEMS) in the cervical esophagus is controversial due to an increased risk of complications. Here we assessed a new type of SEMS purpose-designed for the cervical esophagus area. STUDY: Patients with malignant or benign stenosis within 4 cm distance of the upper esophageal sphincter who underwent placement of a SEMS with a shorter proximal head (Niti-S Esophageal Covered Stent-Cervical-type, NSECSC), were included. Main outcome measures were the functional outcome, tolerance, complications, recurrent dysphagia, and survival. RESULTS: About 37 patients had an NSECSC placed between April 2008 and June 2013 for esophageal stenosis (malignant=20, benign=17), 5 with associated tracheoesophageal fistula. The mean stenosis-upper esophageal sphincter distance was 1.86±1.27 cm. The median follow-up was 150 days. Dysphagia improved in 27/37 cases (73%). Short-term and long-term tolerance without needing stent removal was 92% and 82%, respectively. The complication rate was 59% (22/37): 32% (n=14) major complications [fistula (3), perforation (3), aspiration pneumonia (5), laryngeal dyspnea (2), and bleeding (1)], and 27% (n=10) minor complications [pain (7) or dysphonia (3)]. A multivariate analysis confirmed a higher risk of major complications in cases of benign stenosis (odds ratio=5.2; 95% confidence interval, 1.05-25.90; P=0.04). Recurrent dysphagia occurred in 15 patients (obstruction=7, migration=8). CONCLUSIONS: The NSECSC does not appear less morbid than standard SEMS in the cervical esophageal area, but could be useful in malignant indications as it is well-tolerated and offers effective palliation of the dysphagia. However, this device should not be used in benign cervical esophageal strictures or fistulas.

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 Crohn's 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.

Usefulness of EUS-guided fine needle aspiration biopsy in the diagnosis of suspected or recurring lymphoproliferative disorders.

BACKGROUND: EUS-guided fine needle aspiration biopsy (EUS-FNAB) of deep-seated lymphadenopathy is proposed to identify lymphoproliferative disorders when no superficial lesion is accessible. METHODS: We analyzed prospectively collected data of 115 EUS-FNABs from 73 thoracic or abdomino-pelvic targets in 52 patients with suspected lymphoproliferative disorders (LPDs) between January 2005 and May 2011 from a single institution. Conventional histology and immunohistochemistry procedures were performed on samples. RESULTS: No complications were recorded. An LPD was identified in 29 cases and ruled out in 21 cases. In 2 cases the analysis was negative, but an LPD was identified using a secondary procedure. For the identification of LPDs irrespective of subtype, this procedure has positive and negative predictive values of 100% and 91.3% respectively, with 93.6% sensitivity and 100% specificity. In 31 patients finally diagnosed with LPDs, an accurate diagnosis meeting the 2008 World Health Organization classification criteria was established in 21 (68%) cases, success being significantly associated with target size above 30 mm in multivariate analysis (odds ratio 7.47; p = 0.05). CONCLUSION: EUS-FNAB of deep-seated lymphadenopathy with conventional morphological assessment appears to have a high diagnostic value for LPD identification and can obviate invasive surgery. A sub-classification was possible in two thirds of the cases.

Factors influencing acute infusion reactions in inflammatory bowel disease patients treated with infliximab in the era of scheduled maintenance therapy.

BACKGROUND: An acute infusion reaction during infliximab infusions could lead to drug withdrawal and limit the therapeutic armamentarium in inflammatory bowel diseases. AIM: To determine the risk and protective factors of an acute infusion reaction. MATERIALS AND METHODS: Data were retrieved retrospectively from electronic charts of patients from the 'Clermont-Ferrand IBD cohort'. RESULTS: Among 80 patients, including 51 (63.8%) patients with Crohn's disease, 23 (28.8%) experienced an acute infusion reaction. In multivariate analysis, the Crohn's disease nonstricturing nonfistulizing phenotype predicted an acute infusion reaction (odds ratio=11.40, 95% confidence interval 1.5-87.6; P=0.019).Among 1107 infusions, we observed 38 acute infusion reactions (3.4%). In multivariate analysis, only resumption of infliximab after drug holiday was a major risk factor (odds ratio=24.87, 95% confidence interval 4.4-140.0; P<0.001). Concomitant premedication or immunosuppressant therapies did not prevent an acute infusion reaction.The patients who experienced an acute infusion reaction had a trend toward a higher rate of infliximab discontinuation (69.6 vs. 50.9%, P=0.14). CONCLUSION: An acute infusion reaction is a major event in the history of inflammatory bowel diseases patients treated with infliximab as it could lead to drug discontinuation and thus limits the therapeutic armamentarium considerably. The resumption of infliximab after drug holiday is a major risk factor for an acute infusion reaction. Premedication efficacy remains questionable and should be limited to these high-risk patients.

Monocyte-derived macrophages from Crohn's disease patients are impaired in the ability to control intracellular adherent-invasive Escherichia coli and exhibit disordered cytokine secretion profile.

BACKGROUND: Ileal lesions of Crohn's disease [CD] patients are colonised by adherent-invasive Escherichia coli [AIEC] able to survive in macrophage cell lines. We analysed the ability of monocyte-derived macrophages [MDM] from CD patients to control AIEC intracellular replication and the pro-inflammatory cytokine response of the infected-MDM. METHODS: Peripheral blood MDM were obtained from 24 CD genotyped for NOD2 and ATG16L1 mutations, 5 ulcerative colitis [UC] patients and 12 healthy controls [HC]. The numbers of intracellular bacteria were determined using gentamicin assay. Cytokine secretion was quantified by ELISA assay. RESULTS: We observed that higher levels of bacteria were internalised within MDM from CD patients than MDM from HC or UC patients. MDM from CD patients were unable to restrict AIEC intracellular replication. Infection of MDM from CD patients with AIEC resulted in significantly increased secretion of IL-6 and tumour necrosis factor alpha [TNF α] than did infection with non-pathogenic E. coli. AIEC-infected MDM from CD patients exhibited a disordered cytokines secretion compared with MDM from UC patients and HC. AIEC-infected MDM from patients with quiescent CD released significantly higher amounts of IL-6 and TNF-alpha than those with active disease or those from HC. The level of secreted TNF-alpha was correlated to the number of intracellular AIEC in MDM from CD patients. Treatment of MDM with infliximab did not change the MDM behaviour. CONCLUSIONS: MDM from CD patients are unable to restrict intracellular AIEC replication, leading to disordered inflammatory response influenced by disease activity.