Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application.

Evolution of treatment targets in IBD has increased the need for objective monitoring of disease activity to guide therapeutic strategy. Although mucosal healing is the current target of therapy in IBD, endoscopy is invasive, expensive and unappealing to patients. GI ultrasound (GIUS) represents a non-invasive modality to assess disease activity in IBD. It is accurate, cost-effective and reproducible. GIUS can be performed at the point of care without specific patient preparation so as to facilitate clinical decision-making. As compared with ileocolonoscopy and other imaging modalities (CT and MRI), GIUS is accurate in diagnosing IBD, detecting complications of disease including fistulae, strictures and abscesses, monitoring disease activity and detecting postoperative disease recurrence. International groups increasingly recognise GIUS as a valuable tool with paradigm-changing application in the management of IBD; however, uptake outside parts of continental Europe has been slow and GIUS is underused in many countries. The aim of this review is to present a pragmatic guide to the positioning of GIUS in IBD clinical practice, providing evidence for use, algorithms for integration into practice, training pathways and a strategic implementation framework.

Transperineal Ultrasound for Perianal Fistulas and Abscesses - A Systematic Review and Meta-Analysis.

Purpose Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying perianal fistulae and abscesses. Method The National Library of Medicine and Embase were searched for articles on TPUS for the assessment of idiopathic and Crohn's perianal fistulae and abscesses. Two reviewers independently reviewed eligible studies and rated them for quality using the QUADAS tool. The primary outcome measure was the accuracy of TPUS as measured by its sensitivity and positive predictive value (PPV) in detecting and classifying perianal fistulae, internal openings and perianal abscesses. Results We included 12 studies (565 patients). Overall, the methodological quality of the studies was suboptimal. 3 studies were retrospective and 4 showed significant risks of bias in the application of the reference standard. The sensitivity of TPUS in detecting perianal fistulae on a per-lesion basis was 98 % (95 % CI 96 - 100 %) and the PPV was 95 % (95 % CI 90 - 98 %). The detection of internal openings had a sensitivity of 91 % (95 % CI 84 - 97 %) with a PPV of 87 % (95 % CI 76 - 95 %). The classification of fistulae yielded a sensitivity of 92 % (95 % CI 85 - 97 %) and a PPV of 92 % (95 % CI 83 - 98 %). TPUS had a sensitivity of 86 % (95 % CI 67 - 99 %) and PPV of 90 % (95 % CI 76 - 99 %) in the detection of perianal abscesses. Conclusion The current literature on TPUS illustrates good overall accuracy in the assessment of perianal fistulae and abscesses. However, many studies had methodological flaws suggesting that further research is required.

Failure of gastroenterologists to apply intestinal ultrasound in inflammatory bowel disease in the Asia-Pacific: a need for action.

Intestinal ultrasound (IUS) is a cheap, noninvasive, risk-free procedure that is significantly underutilized in the diagnosis and management of patients with inflammatory bowel disease (IBD) in the Asia-Pacific region. More cost-effective methods of monitoring disease activity are required in light of the increasing global burden of IBD (especially in Asia), the advent of personalized medicine, and the rising cost of healthcare. IUS is a prime example of a technique that meets these needs. Its common clinical applications include assessing the activity and complications of IBD. In continental Europe, countries such as Germany and Italy use this imaging tool as the standard of care and have integrated it into management protocols. There are formal training programs in these countries to train gastroenterologists in IUS, and it is used in an outpatient setting during patient consultations. Barriers to its use in the Asia-Pacific region include lack of experience and research data, and there are few established centers with active training programs. These concerns can be addressed by investing more in IUS service provision and by increasing allocation of resources toward local research and training. Increased uptake of IUS will ultimately benefit patients with IBD.

Perianal disease is associated with psychiatric co-morbidity in Crohn's disease in remission.

BACKGROUND AND AIM: Crohn's disease is a life-long inflammatory disease which can impair quality of life, in particular in patients with psychiatric co-morbidities such as depression and anxiety. The aim of this prospective cohort study was to assess the prevalence of depression and anxiety and related risk factors in patients with quiescent Crohn's disease. METHODS: A consecutive series of adult patients with confirmed diagnosis of Crohn's disease, in clinical remission, were included and investigated during ambulatory visits using a standard questionnaire assessing demographic and clinical features of the disease. Within 1 month after the ambulatory visit, all patients were interviewed by phone to assess the presence of psychiatric disorders using standardized questionnaires. The questionnaire assessed the development of psychiatric disorders after the diagnosis of Crohn's disease, the use of antidepressant or antianxiety therapy and current anxiety or depression by means of the Hospital Anxiety and Depression Scale. RESULTS: One hundred and ninety-five patients were included. Seventy-two (36.9 %) patients showed anxiety and/or depression symptoms, 46 (23.6 %) patients showed anxiety symptoms, 6 (3.1 %) patients showed depression symptoms and 20 (10.3 %) patients showed both symptoms. Forty-eight of these patients (58 %) were without any antidepressive or antianxiety treatment. Anxiety with or without depression was significantly correlated with female sex (p = 0.017), history of perianal disease (p = 0.003) and perianal surgery (p = 0.042). CONCLUSION: Anxiety is a frequent, often untreated, condition in patient affected by Crohn's disease in clinical remission. Female sex, history of perianal disease and perianal surgery are major risk factors for anxiety.

Effect of point-of-care gastrointestinal ultrasound on decision-making and management in inflammatory bowel disease.

BACKGROUND: Gastrointestinal ultrasound is increasingly used for point of care assessment of inflammatory bowel disease. AIMS: To explore the utility of gastrointestinal ultrasound as a point-of-care assessment tool from the perspectives of the clinician and patient. METHODS: A prospective, observational cohort study was designed utilising routine outpatient consultations. Adult patients with inflammatory bowel disease were allocated to receive gastrointestinal ultrasound or not at the discretion of their treating clinician. Patients completed self-reported session experience questionnaires at study entry, immediately after their consultation, and 4 and 16 weeks later. Clinicians reported disease activity status, therapeutic decisions and clinical management. RESULTS: Of 259 participants, mean age 40 (SD: 13) years, 54% male, 73 (28%) underwent ultrasound. Time since diagnosis was 9.2 (8.5) years (ultrasound) and 11.3 (9.2) years (no ultrasound). Immediately after ultrasound, patients who self-reported active disease reported better understanding of all aspects of their disease and disease symptoms were more confident in their ability to make informed decisions about managing their disease and had improved knowledge domain scores compared with the non-ultrasound group (all P < 0.05). Ultrasound had no influence over the patients' ability to manage their own healthcare but tended to be associated with transient improvement in medication adherence. After the ultrasound, the clinician's assessment of patient's disease activity changed in 22% (16/73) and management was altered in 56% (41/73) with anti-inflammatory therapy escalated in 33. About 47% (23/49) patients with Crohn's disease had their medication changed in the ultrasound group, compared to only 22% (25/112) in the nonultrasound group (P = 0.002). For patients with ulcerative colitis, medications were altered in 68% (15/22) compared to 26% (24/70) in the nonultrasound group (P = 0.005) When stratified for disease activity, medication change was more likely in those having ultrasound (P = 0.024). CONCLUSIONS: Point-of-care gastrointestinal ultrasound has the potential to enhance the clinical management of inflammatory bowel disease by contributing to clinician decision-making and education of patients regarding their disease.

Standardisation of intestinal ultrasound scoring in clinical trials for luminal Crohn's disease.

BACKGROUND: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn's disease (CD). However, there is no widely accepted luminal disease activity index. AIMS: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials. METHODS: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1-9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting. RESULTS: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions. CONCLUSIONS: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed.

How to perform gastrointestinal ultrasound: Anatomy and normal findings.

Gastrointestinal ultrasound is a practical, safe, cheap and reproducible diagnostic tool in inflammatory bowel disease gaining global prominence amongst clinicians. Understanding the embryological processes of the intestinal tract assists in the interpretation of abnormal sonographic findings. In general terms, the examination principally comprises interrogation of the colon, mesentery and small intestine using both low-frequency and high-frequency probes. Interpretation of findings on GIUS includes assessment of bowel wall thickness, symmetry of this thickness, evidence of transmural changes, assessment of vascularity using Doppler imaging and assessment of other specific features including lymph nodes, mesentery and luminal motility. In addition to B-mode imaging, transperineal ultrasonography, elastography and contrast-enhanced ultrasonography are useful adjuncts. This supplement expands upon these features in more depth.

Splanchnic Hemodynamics and Intestinal Vascularity in Crohn's Disease: An In Vivo Evaluation Using Doppler and Contrast-Enhanced Ultrasound and Biochemical Parameters.

Crohn's disease (CD) is characterized by inflammation and angiogenesis of affected bowel. We evaluated the correlation among vascularity of intestinal wall in CD, splanchnic hemodynamics, clinical activity and biochemical parameters of inflammation and angiogenesis. Sixteen patients with ileal CD and 10 healthy controls were investigated by means of Doppler ultrasound of the superior mesenteric artery and color Doppler and contrast-enhanced ultrasound of the ileal wall. In parallel, serum levels of vascular endothelial growth factor, tumor necrosis factor-α (TNF-α) and nitric oxide, before and 30 min after a standard meal, were evaluated. In CD patients, there was a significant post-prandial reduction in the resistance index and pulsatility index of the superior mesenteric artery, associated with increased levels of nitric oxide and decreased amounts of TNF-α. A correlation was observed between vascular endothelial growth factor and contrast-enhanced ultrasound parameters of intestinal wall vascularity (r = 0.63-0.71, p < 0.05) and between these parameters and superior mesenteric artery blood flow after fasting (resistance and pulsatility indexes: r = -0.64 and -0.72, p < 0.05). Our results revealed a post-prandial increase in nitric oxide and decrease in TNF-α in CD patients in vivo. They also confirm the role of vascular endothelial growth factor in angiogenesis and in pathologic vascular remodeling of CD and its effect on splanchnic blood flow.

WFUMB Position Paper. Learning Gastrointestinal Ultrasound: Theory and Practice.

Gastrointestinal ultrasound (GIUS) is an ultrasound application that has been practiced for more than 30 years. Recently, GIUS has enjoyed a resurgence of interest, and there is now strong evidence of its utility and accuracy as a diagnostic tool for multiple indications. The method of learning GIUS is not standardised and may incorporate mentorship, didactic teaching and e-learning. Simulation, using either low- or high-fidelity models, can also play a key role in practicing and honing novice GIUS skills. A course for training as well as establishing and evaluating competency in GIUS is proposed in the manuscript, based on established learning theory practice. We describe the broad utility of GIUS in clinical medicine, including a review of the literature and existing meta-analyses. Further, the manuscript calls for agreement on international standards regarding education, training and indications.

The impact of symptoms, irritable bowel syndrome pattern and diagnostic investigations on the diagnostic delay of Crohn's disease: A prospective study.

BACKGROUND: We investigated symptoms and tests performed prior to a formal diagnosis of Crohn's disease and the reasons for diagnostic delay. METHODS: Consecutive patients recently diagnosed with Crohn's disease were enrolled between October 2012 and November 2013. Clinical data, symptoms including Rome III criteria at onset and at diagnosis, location and disease phenotype were recorded. Faecal calprotectin, radiological and endoscopic examinations performed prior to diagnosis were analysed. Diagnostic delay, stratified into tertiles and median time, was analysed using parametric and nonparametric tests. RESULTS: 83 patients (49.4% males, median age 31 years) were enrolled. The median diagnostic delay was 8 (0-324) months. Twenty-six patients did not consult a general practitioner until diagnosis (31.3%), 18 presented to the emergency department (21.7%) and 8 directly to a gastroenterologist (9.6%). Diagnostic delay was not associated with specific symptoms. However, patients with bloating at presentation had a longer delay compared to those who did not (median, 6.1 vs. 16.8 months, respectively; p=0.016). Nineteen patients underwent incomplete ileocolonoscopies (22.9%) and 7 had no biopsies (8.4%), with a consequent diagnostic delay (median, 24 and 24 vs. 6 months, respectively; p=0.025 and p=0.008). CONCLUSION: Diagnostic delay for Crohn's disease is significantly associated with incomplete ileocolonoscopies, but not with symptoms, except bloating at presentation.

Optimizing conventional medical therapies in inflammatory bowel disease in 2014.

Goals of therapy for inflammatory bowel disease have advanced beyond symptom control to the normalization of biomarkers of inflammation, and mucosal healing in particular, with the expectation that this will change the natural history of these diseases. Concurrent with higher treatment expectations has come an expanded therapeutic armamentarium to achieve these goals, and a greater ability to optimize each therapeutic class to maximize therapeutic benefits and minimize unnecessary treatment failures. In addition to these advances has come the evolution of therapeutic drug monitoring which is increasingly being utilized to optimize the use of immunomodulators and biologic therapies in particular. This review will outline the principals of optimization of the conventional medical therapies available to the clinician today.

Ulcerative colitis: current pharmacotherapy and future directions.

INTRODUCTION: Ulcerative colitis (UC) is a chronic relapsing disease, characterised by alternating of acute and remission phases. Although the aetiology is unknown, in recent years, there has progressively been greater knowledge of the various pathogenetic mechanisms underlying the disease itself. Thus, from therapy based on generically anti-inflammatory or immunosuppressive agents, treatment is gradually moving towards drugs that selectively block specific inflammatory mediators, such as TNF-α. AREAS COVERED: This review provides the most significant data about the therapeutic role of different drugs currently available for the treatment of UC. In addition, the critical therapeutic areas on which research could focus in the near future are discussed. EXPERT OPINION: UC is a disease affecting young patients, whose quality of life may be strongly compromised by the progression of disease. Over time, the disease may lead to an impairment of the normal anatomy and physiology of the colon, and the cumulative incidence of dysplasia and colorectal cancer increases with the time. Thus, the main aims of the near future should be both a better definition of patients at risk for a poor clinical course and progression of disease, and the development of a much more aggressive treatment for patients with a poor prognosis.