José María Paredes

Accuracy of Magnetic Resonance Enterography in Assessing Response to Therapy and Mucosal Healing in Patients With Crohn's Disease

BACKGROUND & AIMS We assessed the accuracy of magnetic resonance enterography (MRE) in monitoring response to therapy in patients with Crohns disease (CD) using ileocolonoscopy as a reference standard. METHODS We performed a prospective multicenter study of 48 patients with active CD and ulcers in at least one ileocolonic segment. All patients underwent ileocolonoscopy and MRE at baseline and 12 weeks after completing treatment with corticosteroids (CS) or anti-tumor necrosis factor agents. Disease activity was quantified using Crohns Disease Endoscopic Index of Severity (CDEIS) and Magnetic Resonance Index of Activity (MaRIA). The primary analysis was to determine the accuracy of MRE in identification of healing, defined as the disappearance of ulcers in endoscopy examination. Additional analyses established the accuracy of MRE in determining endoscopic remission (a CDEIS score <3.5) and change in severity based on consideration of all segments. RESULTS MRE determined ulcer healing with 90% accuracy and endoscopic remission with 83% accuracy. The mean CDEIS and MaRIA scores significantly changed at week 12 in segments with ulcer healing, based on endoscopic examination (CDEIS: 21.28 ± 9.10 at baseline vs 2.73 ± 4.12 at 12 weeks; P < .001 and MaRIA: 18.86 ± 9.50 at baseline vs 8.73 ± 5.88 at 12 weeks; P < .001). The MaRIA score accurately detected changes in lesion severity (Guyatt score: 1.2 and standardized effect size: 1.07). MRE was as reliable as endoscopy in assessing healing; no significant changes in CDEIS or MaRIA scores were observed in segments with persistent ulcers, based on endoscopic examination (CDEIS: 26.43 ± 9.06 at baseline vs 20.77 ± 9.13 at 12 weeks; P = .18 and MaRIA: 22.13 ± 8.42 at baseline vs 20.77 ± 9.17 at 12 weeks; P = .42). The magnitude of change in CDEIS scores correlated with those in MaRIA scores (r = 0.51; P < .001). CONCLUSIONS MRE evaluates ulcer healing with a high level of accuracy when ileocolonoscopy is used as the reference standard. The MaRIA is a valid, responsive, and reliable index assessing response to therapy in patients with CD.

Crohn Disease: Correlation of Findings at Contrast-enhanced US with Severity at Endoscopy

PURPOSE To evaluate the effectiveness of visualization of vascularization at contrast material-enhanced ultrasonography (US) for assessment of the activity of Crohn disease, with severity grade determined at endoscopy as the reference standard. MATERIALS AND METHODS Ethics committee approval and written informed consent were obtained. Sixty-one patients (age range, 21-67 years; median age, 36 years) who had Crohn disease underwent both colonoscopy and US, including color Doppler and contrast-enhanced US, prospectively. To assess the vascularization of the involved bowel loop in a region expected to be seen at colonoscopy, the contrast agent uptake was measured by using quantitative analysis of the enhancement in regions of interest. Measurement of contrast enhancement was assessed as the increase in wall brightness with respect to the baseline brightness. Results were compared with the severity grade determined at endoscopy by using the area under the receiver operating characteristic curve and logistic regression analysis. RESULTS Colonoscopy showed inflammatory lesions in 53 patients (mild disease, seven; moderate disease, 12; and severe disease, 34). Bowel wall thickness and grade at color Doppler US (P = .019 and .002, respectively) correlated with severity grade at endoscopy. Mural contrast enhancement in patients with active disease at endoscopy was markedly increased in comparison with enhancement in patients with inactive disease (P < .001). Multivariate logistic regression analysis revealed that an increase in wall brightness was a significant and independent variable predictive of severity grade at endoscopy. A threshold brightness value of percentage of increase of 46% had a sensitivity and specificity of 96% and 73%, respectively, in the prediction of moderate or severe grade for inflammation at endoscopy. CONCLUSION Quantitative measurements of bowel enhancement obtained by using contrast-enhanced US correlate with severity grade determined at endoscopy. Contrast-enhanced US could be a useful technique to monitor the activity of Crohn disease. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531082269/-/DC1.

Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal inflammation in Crohn's disease: a comparison with surgical histopathology analysis.

BACKGROUND Differentiation between predominantly inflammatory versus fibrous-predominant lesions is particularly important in order to decide the optimal therapy in patients with refractory symptoms in Crohns disease (CD). OBJECTIVE The purpose of this investigation was to evaluate the accuracy of several US parameters, especially of contrast-enhanced US, for evaluation of mural inflammation in CD, with histopathology as the reference. MATERIALS AND METHODS Preoperative ultrasound examination, including contrast-enhanced ultrasound (CEUS) was performed in 25 consecutive patients with Crohns disease undergoing elective bowel resection. Ultrasound variables, such as wall thickness, transmural complications, colour Doppler grade, quantitative analysis of the enhancement and the presence and severity of strictures, were prospectively evaluated and compared with the histopathology results. Histopathology grading of acute inflammation using the acute inflammatory score and the degree of fibrostenosis was performed in each segment and the results were compared with all the US variables as well as with a previously defined ultrasound score system for inflammatory and fibrostenotic changes. RESULTS 28 segments were analysed. In pathology analysis there were 12 predominantly inflammatory segments, 9 predominantly fibrostenotic and 7 compound lesions. When the pathology score was dichotomised into two groups (inflammatory and fibrostenotic) the number of stenoses correctly classified by US was 23 out 28, with a substantial agreement (kappa=0.632). There was a good correlation between the sonographic and pathology scores, both inflammation (Spearmans, r=0.53) and fibrostenosis (Spearmans, r=0.50). Transmural complications, colour Doppler grade and percentage of increase in contrast enhancement were significantly associated with the pathology inflammatory score (p=0.018, p=0.036 and p=0.005, respectively). There was a significantly negative association between the colour Doppler grade and the pathologic fibrostenotic score. CONCLUSIONS Ultrasound, including CEUS, can be a useful tool for distinguishing inflammatory from fibrostenotic lesions in CD. This information can be useful in the management of CD.

Contrast-enhanced ultrasonography: Usefulness in the assessment of postoperative recurrence of Crohn's disease

AIM The aim of this study was to assess whether the contrast-enhanced ultrasonography (CEUS) can increase the value of the ultrasonography in the study of postoperative recurrence of Crohns disease (CD). MATERIALS AND METHODS 60 patients with CD who had previously undergone ileocolic resection underwent prospectively both CEUS and colonoscopy within a 3-day period. The sonographic examination included evaluation of bowel wall thickness, transmural complications, colour Doppler grade and contrast-enhanced US. In addition a sonographic score was established. The capacity of CEUS to diagnose endoscopic recurrence, as well as its severity, was assessed by calculating the sensitivity, specificity and positive and negative predictive values, accuracy and odds ratio, with their respective 95% confidence intervals. The areas under the receiver operating characteristic (ROC) curves were also calculated. RESULTS 49 out of 60 patients showed endoscopic postoperative recurrence. Severe endoscopic recurrence was present in 34 patients (57%). Classic ultrasound parameters (wall thickness >3mm and colour Doppler flow) revealed an accuracy of 88.3% for the diagnosis of recurrence. Sonographic score 2, including thickness >5mm or contrast enhancement >46%, improved the results with a sensitivity, specificity and accuracy of 98%, 100% and 98.3%, respectively, in the diagnosis of endoscopic recurrence. The area under the ROC curve was 0.99, in remarkable agreement with endoscopy (k: 0.946). Sonographic score 3, including thickness >5mm, contrast enhancement >70% or fistula identified 32 out of 34 (94.1%) severe endoscopic recurrences. The area under the ROC curve was 0.836, in good agreement with endoscopy (k: 0.688). CONCLUSION CEUS shows excellent sensitivity and specificity for the diagnosis of postoperative recurrence in CD and can also detect severe recurrences.

Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: Changes following treatment with immunomodulators and/or anti-TNF antibodies

OBJECTIVE The objective of this study was to analyze the accuracy of abdominal ultrasonography (AUS) in the assessment of mucosal healing in patients with Crohns disease (CD) receiving immunomodulators and/or biological treatment, with ileocolonoscopy as the reference standard. MATERIALS AND METHODS Thirty patients were included in a prospective longitudinal study. All patients underwent ileocolonoscopy and AUS before and after a minimum of one year of treatment. The Crohns Disease Endoscopic Inflammatory Index of Severity (CDEIS) was used for endoscopic assessment whereas AUS was analyzed by means of bowel wall thickness, color Doppler grade and percentage of increase of parietal enhancement after contrast injection. RESULTS In the segmental analysis, endoscopic healing was found in 71.2% of the segments and AUS findings were normalized in 62.8%, with a significant correlation between the two techniques (κ=0.76, p<0.001). In the overall assessment performed after treatment, 18 (60%) patients exhibited endoscopic remission (CDEIS <6 points); of these patients, 15 (83.3%) had normalized sonographic findings, with a good correlation between endoscopic remission and sonographic normalization (κ=0.73, p<0.001). Of the three variables assessed by AUS, parietal thickness was the best variable to predict mucosal healing in both analyses, segmental and global. CONCLUSION Abdominal ultrasonography is a useful and reliable technique for the assessment of the endoscopic response to treatment with immunomodulators and/or biological drugs in Crohns disease. AUS is a highly accurate technique for evaluating the healing of the intestinal mucosa.

Contrast-enhanced ultrasound (CEUS) in Crohn’s disease: technique, image interpretation and clinical applications

BackgroundRecent meta-analysis has demonstrated no significant differences in diagnostic accuracy among different imaging techniques (US, MRI and CT) in the evaluation of Crohn’s disease (CD). High-resolution bowel ultrasound has emerged as an alternative imaging technique for the diagnosis and follow-up of patients with CD, being as accurate as CT and MR for detecting intramural and extramural extension of the disease. B-Mode US can evaluate the localization and length of the affected intestinal segments and allow identification of transmural complications, stenosis and intestinal obstruction. Doppler techniques are tools that visualize and quantify bowel vascularization. Contrast-enhanced ultrasound (CEUS) is a new technique that involves IV administration of an ultrasound contrast agent with real-time examination, providing an accurate depiction of the bowel wall microvascularization and the perienteric tissues. The introduction of imaging quantification techniques enables an objective quantitative measurement of the enhancement.Method and resultsThe article reviews the technique, sonographic findings, advantages and limitations, and clinical applications of contrast-enhanced US in the evaluation of Cohn’s disease. Current CEUS applications in CD are: CD activity assessment, evaluation of inflammatory masses, distinguishing phlegmons from abscesses, characterization of stenosis by differentiating fibrosis from inflammation, monitoring the efficacy of drug treatments and improving the detection of disease recurrence.ConclusionCEUS is an emerging technique that is part of the entire sonographic evaluation, with a role in the diagnosis and follow-up of CD, thus improving therapy planning and monitoring of the efficacy of treatment.

Non-invasive diagnosis and grading of postsurgical endoscopic recurrence in Crohn's disease Usefulness of abdominal ultrasonography and 99m Tc-hexamethylpropylene amineoxime-labelled leucocyte scintigraphy

UNLABELLED Non-invasive techniques aim to be an alternative to endoscopy in the assessment of postsurgical recurrence of Crohns disease (CD). The object of this study was to evaluate the accuracy of abdominal ultrasonography (AUS) and (99m)Tc-hexamethylpropylene amineoxime ((99m)Tc-HMPAO)-labelled leucocyte scintigraphy (LLS) compared with endoscopy in the diagnosis and grading of postsurgical recurrence of CD. Between January 2006 and May 2007, all patients with CD and resection with ileocolic anastomosis were included prospectively. Within three days they underwent an ileocolonoscopy, AUS with evaluation of bowel wall thickness and the presence of Doppler flow, and LLS. Forty patients who met the study conditions were included; 5 patients did not agree to have the ileocolonoscopy and it was not possible to assess the anastomosis in 2 patients. Endoscopic recurrence was detected in 26 patients (78.8%), in 15 of whom it was moderate-severe. For the diagnosis of recurrence, both AUS and LLS showed acceptable sensitivity and positive predictive value, with an accuracy of 72.7% and 78.1%, respectively. The results of the AUS and LLS for diagnosing moderate-severe recurrence were better, with an accuracy of 78.8% and 81.3%, respectively. The best assessment of the severity of the recurrence was obtained with the combination of both techniques (sensitivity, specificity, positive and negative predictive values, accuracy and kappa index were, respectively: 93.3%, 72.2%, 73.7%, 92.9%, 81.8% and 0.64). The variables evaluated, both sonographic and scintigraphic, had areas under the curve that were similar and significantly different from 0.5. CONCLUSION Abdominal ultrasonography and (99m)Tc-HMPAO-labelled leucocyte scintigraphy are two useful non-invasive techniques for the assessment of postsurgical recurrence of Crohns disease.

Accuracy of MRI to Assess Therapeutic Responses and Mucosal Healing in Crohn's Disease

to a change in their management. Findings unrelated to IBD were reported in 14% that warranted further investigations or consultations (including 3 new cancers). Conclusions: Crohns disease of the TI can be missed at ileoscopy either due to skipping of the distal TI or due to disease confined to the intramural portion of the bowel wall. CTE complements ileocolonoscopy in assessing disease activity in patients with Crohns disease.

Ultrasonographic Changes at 12 Weeks of Anti-TNF Drugs Predict 1-year Sonographic Response and Clinical Outcome in Crohnʼs Disease: A Multicenter Study

Background:The objective was to assess the long-term effect of biological treatment on transmural lesions of Crohns disease evaluated with ultrasound, including contrast-enhanced ultrasound. Methods:Fifty-one patients with active Crohns disease were included in a prospective multicenter longitudinal study. All patients underwent a clinical assessment and sonographic examination at baseline, 12 weeks after treatment initiation, and after 1-year of treatment. Patients were clinically followed at least 2 years from inclusion until the end of the study. Ultrasonographic evaluation included bowel wall thickness, color Doppler grade, parietal enhancement, and presence of transmural complications or stenosis. Sonographic changes after treatment were classified as normalization, improvement, or lack of response. Results:Improvement at 52 weeks was more frequent in patients with improvement at final of induction (12 weeks) compared with patients who did not improve (85% versus 28%; P < 0.0001). One-year sonographic evolution correlated with clinical response; 28 of the 29 (96.5%) patients with sonographic improvement at 52 weeks showed clinical remission or response. Patients without sonographic improvement at 52 weeks of treatment were more likely to have a change or intensification in medication or surgery (13/20, 65%) during the next year of follow-up than patients with improvement on the sonography (3/28, 11%). Stricturing behavior was the only sonographic feature associated to a negative predictive value of response (P = 0.0001). Conclusions:Sonographic response after 12 weeks of therapy is more pronounced and predicts 1-year sonographic response. Sonographic response at 1-year examination correlates with 1-year clinical response and is a predictor of further treatments efficacy, 1-year or longer period of follow-up.

Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study

AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis (UC) and to identify predictors of response. METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at week 0 and 14 with the physician’s global clinical assessment (PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database. RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC (E2) and 70% had extensive UC (E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor (TNF) treatment naïve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at week 14 (a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at week 14. Being anti-TNF treatment naïve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of follow-up. Only three adverse effects (AEs) were observed during the study; all were mild and golimumab was not interrupted. CONCLUSION This real-life practice study endorses golimumab’s promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.