Kerri L. Novak

Review article: dermatological complications of immunosuppressive and anti-TNF therapy in inflammatory bowel disease.

With the expanding list of medications available to treat patients with inflammatory bowel disease (IBD), it is important to recognise adverse events, including those involving the skin. Dermatological adverse events may be confused with extra‐intestinal manifestations of IBD.

Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts.

Background:Bowel ultrasonography (US) is considered a useful technique for assessing mural inflammation and complications in Crohns disease (CD). The aim of this review is to appraise the evidence on the accuracy of bowel US for CD. In addition, we aim to provide recommendations for its optimal use. Methods:Publications were identified by literature search from 1992 to 2014 and selected based on predefined criteria: 15 or more patients; bowel US for diagnosing CD, complications, postoperative recurrence, activity; adequate reference standards; prospective study design; data reported to allow calculation of sensitivity, specificity, agreement, or correlation values; articles published in English. Results:The search yielded 655 articles, of which 63 were found to be eligible and retrieved as full-text articles for analysis. Bowel US showed 79.7% sensitivity and 96.7% specificity for the diagnosis of suspected CD, and 89% sensitivity and 94.3% specificity for initial assessment in established patients with CD. Bowel US identified ileal CD with 92.7% sensitivity, 88.2% specificity, and colon CD with 81.8% sensitivity, 95.3% specificity, with lower accuracy for detecting proximal lesions. The oral contrast agent improves the sensitivity and specificity in determining CD lesions and in assessing sites and extent. Conclusions:Bowel US is a tool for evaluation of CD lesions in terms of complications, postoperative recurrence, and monitoring response to medical therapy; it reliably detects postoperative recurrence and complications, as well as offers the possibility of monitoring disease progression.

Clinical, endoscopic and radiographic outcomes with ustekinumab in medically‐refractory Crohn's disease: real world experience from a multicentre cohort

Ustekinumab is a monoclonal antibody targeting interleukins‐12 and ‐23, with efficacy in Crohns disease (CD) demonstrated in clinical trials.

Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy.

BACKGROUND & AIMS It is unclear what are the best and most appropriate endoscopic procedures for detecting colonic neoplasia in patients with long-term colonic inflammatory bowel disease (IBD). Dye chromoendoscopy (DCE) is the standard used in IBD surveillance colonoscopies. However, studies are needed to determine the optimal endoscopic technique for detecting dysplastic lesions. We investigated current practices used in surveillance colonoscopies by IBD gastroenterologists at a single tertiary center. We also determined the rate of neoplasia detection among different surveillance endoscopic techniques in an analysis of random or targeted biopsies. METHODS We collected data on 454 patients with IBD (54.5% male; mean age, 50 y; mean disease duration, 14.5 y; 55.9% with ulcerative colitis, 42.7% with Crohns disease, and 1.3% with indeterminate colitis) who underwent surveillance colonoscopy from April 2011 through March 2014 at the University of Calgary in Canada. Subjects were examined using white-light standard-definition endoscopy (WLE), high-definition (HD) colonoscopy, virtual electronic chromoendoscopy (VCE), or DCE; random or targeted biopsy specimens were collected. Endoscopic and histologic descriptions with suspected neoplasia were recorded. Rates of neoplasia detection by the different endoscopic procedures were compared using chi-square analysis. RESULTS Of the patients analyzed, 27.7% had WLE endoscopy with random collection of biopsy specimens, 27.3% had HD colonoscopy with random collection of biopsy specimens, 14.1% had VCE with random collection of biopsy specimens, 0.9% had DCE with random collection of biopsy specimens, 12.8% had HD colonoscopy with collection of targeted biopsy specimens, 11.9% had VCE with collection of targeted biopsy specimens, and 5.3% had DCE with collection of targeted biopsy specimens. Neoplastic lesions were detected in 8.2% of the procedures performed in the random biopsy group (95% confidence interval, 5.6-11.7) and 19.1% of procedures in the targeted biopsy group (95% confidence interval, 13.4-26.5) (P < .001). Neoplasias were detected in similar proportions of patients by HD colonoscopy, VCE, or DCE, with targeted biopsy collection. CONCLUSIONS In a large cohort of IBD patients undergoing surveillance colonoscopy, targeted biopsies identified greater proportions of subjects with neoplasia than random biopsies. Targeted collection of biopsy specimens appears to be sufficient for detecting colonic neoplasia in patients undergoing HD colonoscopy, DCE, or VCE, but not WLE.

Clinic-based Point of Care Transabdominal Ultrasound for Monitoring Crohn’s Disease: Impact on Clinical Decision Making

BACKGROUND AND AIMS The use of cross-sectional imaging is important to characterise inflammatory bowel disease [IBD] activity, extent, and location and to exclude complications, regardless of symptoms. The aim of this study was to evaluate the impact of routine use of sonography in the management of inflammatory bowel disease. METHODS A total of 49 patients with Crohns disease were prospectively evaluated. Clinical symptoms (Harvey-Bradshaw Index [HBI]), disease character, serological markers of inflammation [C-reactive protein], and endoscopic evaluation were collected and reviewed by two independent IBD-specialty physicians. Clinical decisions regarding management were recorded. A separate, blinded physician then performed bowel ultrasound [US] and graded disease activity:] as inactive, mild, or active. A second blinded physician read and graded a sub-set of the US images. Clinical decisions of both IBD-physicians after US were independently recorded. Changes in clinical management following US information and inter-rater agreement on US disease activity parameters were evaluated. The concordance between US, CRP and clinical symptoms [HBI] were analysed. Follow-up data after US evaluation were collected. RESULTS Clinical decisions were changed after ultrasound assessment in 30/49 [60%] and 28/48 [58%] of cases, for each physician respectively [p < 0.0001 for each]. Many [59%] of the patients seen in clinic were asymptomatic with an HBI of 3 or less [n = 29]; however, 52% [n = 15] of these had active disease found on US, resulting in alterations in clinical management. The agreement in overall score between the US reviewers was good, ĸ = 0.749 [0.5814, 0.9180], p < 0.001. CONCLUSIONS Clinic-based point of care US can play a significant role in guiding therapeutic management and is an important adjunct to routine clinical and laboratory assessment.

Ultrasound Shear Wave Elastography and Contrast Enhancement: Effective Biomarkers in Crohn's Disease Strictures

Background: Inflammation, fibrosis, and muscular hypertrophy lead to thickened bowel in Crohns disease forming strictures. Ultrasound shear wave elastography (SWE) measures bowel wall stiffness. Contrast-enhanced ultrasound (CEUS) uniquely detects bowel wall inflammation. We aim to correlate SWE of ileal Crohns disease in vivo to CEUS peak enhancement and pathology grades of inflammation, fibrosis, and muscular hypertrophy. Methods: In a prospective institutional review board–approved study, 105 consecutive ileal patients with Crohns disease received ultrasound. At maximal bowel wall thickness (>4 mm), SWE and CEUS were performed. Fifteen patients had ileal resection within a mean time interval of 71.0 ± 66.9 days. Pathology scores for inflammation, fibrosis, and muscular hypertrophy were compared with SWE and CEUS measurements. Results: Mean in vivo SWE velocity for patients with and without surgery was 2.8 ± 0.7 and 2.2 ± 0.8 m/s (P < 0.01), respectively. In all ileal specimens, chronic exceeded active inflammatory change (P < 0.001). There was an inverse relationship between CEUS peak enhancement and both fibrosis, r = −0.59, P = 0.02, and SWE velocity measurements, r = −0.61, P = 0.03. Strictured bowel specimens had more smooth muscle hypertrophy than fibrosis, P < 0.001. There was moderate correlation between SWE and muscular hypertrophy, r = 0.59, P = 0.02 and no significant relationship between SWE and fibrosis scores (P > 0.05). Conclusions: Stiffer bowel from smooth muscle hypertrophy increases SWE measurements. We report a novel relation of high SWE with muscle hypertrophy, and inverse relationship with CEUS peak enhancement; providing differentiation between active and chronic bowel wall inflammation to improve selection between medical therapy and surgery.

Invasive Amoebiasis: A Review of Entamoeba Infections Highlighted with Case Reports

Entamoeba histolytica infections of the gastrointestinal tract are common in the developing world but rare in North America. The authors present two cases: one involving an individual who had not travelled to an endemic area and another involving an individual who was born in Bulgaria. Both presented with severe abdominal pain and diarrhea. Endoscopic assessment revealed scattered colonic ulcerations and one patient was found to have a liver abscess on imaging. Stool ova and parasite studies were negative in both cases and both were diagnosed on review of colonic biopsies. On review of all Entamoeba cases in the Calgary Health Zone (Alberta), ova and parasite analysis found an average of 63.7 Entamoeba cases per year and a pathology database review revealed a total of seven cases of invasive E histolytica (2001 to 2011). Both patients responded well to antibiotic therapy. E histolytica should be considered in new-onset colitis, especially in individuals from endemic areas.

Long-term Maintenance of Clinical, Endoscopic, and Radiographic Response to Ustekinumab in Moderate-to-Severe Crohn's Disease: Real-world Experience from a Multicenter Cohort Study

Background: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. While effective in clinical trials for Crohns disease (CD), long-term maintenance of response in the real-world setting is unclear. We aim to assess the efficacy of ustekinumab for maintaining clinical, endoscopic, and radiographic response in CD. Methods: A retrospective multicenter cohort study was performed on patients with CD achieving steroid-free clinical response to ustekinumab induction, and advanced onto a regularly scheduled maintenance ustekinumab regimen between 2011 and 2016. The primary outcome was loss of response, defined by an increase in Harvey Bradshaw Index of >3 points from baseline requiring ustekinumab dose escalation, reinduction, rescue corticosteroids, immunomodulators, surgery, or ustekinumab discontinuation. Multivariate Cox proportional hazards regression was used to identify clinical factors associated with loss of response. Results: One hundred four patients with CD achieving steroid-free response with ustekinumab induction were included; 92.3% (96/104) had previously failed antitumor necrosis factor therapy. Median follow-up was 57.2 weeks (interquartile range (IQR): 36.7–103.4). Cumulative probability of maintained response at 52 weeks was 71.8%. Sixty-seven patients (64.4%) maintained endoscopic or radiographic response. Thirty-five patients (33.7%) lost response at a median time of 47.4 weeks (IQR: 35.3–68.4). Dose escalation was required in 17 patients (16.3%); response was recaptured in 9/17 (52.9%). Nine patients (8.7%) required surgery. In Cox multivariate regression, concurrent immunomodulation was associated with reduced risk of loss of response (hazards ratio 0.39 (95% CI, 0.17–0.92)). Conclusions: Subcutaneous ustekinumab is an effective treatment option for maintaining long-term clinical, endoscopic, and radiographic response in patients with moderate-to-severe CD failing antitumor necrosis factor therapy.

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy

Objectives:Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy.Methods:A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification.Results:A total of 270 patients (55% men; age range 20–77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98–22.5 and OR 21.50 (8.65–60.10), respectively).Conclusions:In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

Upper gastrointestinal bleeding due to peptic ulcer disease is not associated with air pollution: a case-crossover study.

BackgroundRecent studies have demonstrated an association between short-term elevations in air pollution and an increased risk of exacerbating gastrointestinal disease. The objective of the study was to evaluate if day-to-day increases in air pollution concentrations were positively associated with upper gastrointestinal bleeding (UGIB) secondary to peptic ulcer disease (PUD).MethodsA time-stratified case-crossover study design was used. Adults presenting to hospitals with their first UGIB secondary to PUD from 2004–2010 were identified using administrative databases from Calgary (n = 1374; discovery cohort) and Edmonton (n = 1159; replication cohort). Daily concentrations of ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and particulate matter (PM10 and PM2.5) were estimated in these two cities. Conditional logistic regression models were employed, adjusting for temperature and humidity. Odds ratios (OR) with 95 % confidence intervals (CI) were expressed relative to an interquartile range increase in the concentration of each pollutant.ResultsNo statistically significant associations were observed for any of the individual pollutants based on same-day, or 1-day lag effects within the Calgary discovery cohort. When the air pollution exposures were assessed as 3-, 5-, and 7-day averages, some pollutants were inversely associated with UGIB in the discovery cohort; for example, 5-day averages of nitrogen dioxide (OR = 0.68; 95 % CI: 0.53–0.88), and particulate matter <2.5 μm (OR = 0.75; 95 % CI: 0.61–0.90). However, these findings could not be reproduced in the replication cohort.ConclusionOur findings suggest that short-term elevations in the level of ambient air pollutants does not increase the incidence of UGIB secondary to PUD.