Gaetano Cristian Morreale

INFLAMMATION IN IRRITABLE BOWEL SYNDROME: MYTH OR NEW TREATMENT TARGET?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.

The real-world effectiveness of vedolizumab on intestinal and articular outcomes in inflammatory bowel diseases

BACKGROUNDnThe effectiveness of vedolizumab in real-world practice is under evaluation, while its role in inflammatory bowel disease-associated spondyloarthritis is still unclear.nnnAIMSnTo report real-world data about the effectiveness of vedolizumab on intestinal and articular symptoms after 10 and 22 weeks of treatment.nnnMETHODSnWeb-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a prospective multicentre observational study.nnnRESULTSn163 patients (84 with Crohns disease and 79 with ulcerative colitis) were included. At week 10, a steroid-free remission was achieved in 71 patients (43.6%), while at week 22 a steroid-free remission was obtained in 40.8% of patients. A response on articular symptoms was reported after 10 weeks of treatment in 17 out of 43 (39.5%) patients with active spondyloarthritis at baseline, and in 10 out of 22 (45.4%) patients at week 22. The only factor associated with articular response was the coexistence of clinical benefit on intestinal symptoms (at week 10: OR 8.471, pu202f=u202f0.05; at week 22: OR 5.600, pu202f=u202f0.08).nnnCONCLUSIONSnVedolizumab showed good effectiveness after 10 and 22 weeks of treatment. A subset of patients reported improvement also on articular symptoms, probably as a consequence of the concomitant control of gut inflammation.

The Role of Laboratory Tests in Crohn’s Disease

In the past, laboratory tests were considered of limited value in Crohns disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies.

Elderly Onset Celiac Disease: A Narrative Review.

Celiac sprue is a chronic disease, which usually occurs in children and young adults. However, it can develop in any age group, and the prevalence is increasing even in the elderly population. The atypical patterns of clinical presentation in this age group sometimes can cause a delay in diagnosis. Given the lower sensitivity and specificity of serological tests in the aged population, clinical suspect often arises in the presence of complications (autoimmune disorders, fractures, and finally, malignancy) and must be supported by endoscopic and imaging tools. In this review, we highlight the incidence and prevalence of celiac disease in the elderly, the patterns of clinical presentation, diagnosis, and the most frequent complications, with the aim of increasing awareness and reducing the diagnostic delay of celiac disease even in the elderly population.

Superior Mesenteric Artery Syndrome: Clinical, Endoscopic, and Radiological Findings

Background The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. Aims and Methods This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these cases with a control group consisting of 10 cases out of 2380 EGDS of initially suspected (but not radiologically confirmed) SMA over a follow-up 2-year period (2015-2016). Results The prevalence of SMA syndrome was 0.005%. Median age and body mass index were 23.5 years and 21.5u2009kg/m2, respectively. Symptoms developed between 6 and 24 months. Median aortomesenteric angle and aorta-SMA distance were 22 and 6u2009mm, respectively. All patients improved on conservative treatment. In our series, a marked (>5u2009kg) weight loss (p = 0.006) and a long-standing presentation (more than six months in 80% of patients) (p = 0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT after an endoscopic suspicion. A “resembling postprandial distress syndrome dyspepsia” presentation may be helpful to the endoscopist in suspecting a latent SMA syndrome (p = 0.02). The narrowing of both the aortomesenteric angle (p = 0.001) and the aortomesenteric distance (p < 0.001) was significantly associated with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing of the aortomesenteric distance seemed to be more accurate, rather than the narrowing of the aortomesenteric angle. Conclusion SMA syndrome represents a diagnostic and therapeutic challenge. Our results show the following findings: the importance of the endoscopic suspicion of SMA syndrome; the preponderance of a long-standing and chronic onset; a female preponderance; the importance of the nutritional counseling for the treatment; no need of surgical intervention; and better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger prospective studies are needed to clarify the best diagnosis and management of the SMA syndrome.

A difficult diagnosis of coeliac disease: Repeat duodenal histology increases diagnostic yield in patients with concomitant causes of villous atrophy

Villous atrophy in absence of coeliac disease (CD)-specific antibodies represents a diagnostic dilemma. We report a case of a woman with anaemia, weight loss and diarrhoea with an initial diagnosis of seronegative CD and a histological documented villous atrophy who did not improve on gluten-free diet due to the concomitant presence of common variable immunodeficiency (CVID) and Giardia lamblia infection. This case report confirms that CD diagnosis in CVID patients is difficult; the combination of anti-endomysial antibodies (EmA-IgA), anti-tissue transglutaminase antibodies (tTG-IgAb) antibodies and total IgA is obligatory in basic diagnostic of CD but in CVID are negative. Furthermore, the typical histological aspects of the intestinal mucosa in CVID (absence of plasma cells and switch to the IgD immunoglobulins), cannot rule out a concomitant CD diagnosis. HLA typing in this setting has a low positive predictive value but should be considered. Histological response to a gluten-free diet on repeat biopsy and the concomitant treatment of other causes of villous atrophy leads to a definite diagnosis of CD.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.

Laboratory Tests in Crohn’s Disease

Laboratory tests are useful for diagnosing Crohn’s disease, assessing disease activity, identifying complications, and monitoring response to therapy. Their role has been considered limited in the past due to lack of specificity. The introduction of biological therapies in inflammatory bowel disease (IBD) has renewed interest in inflammatory markers, especially C-reactive protein (CRP), given their potential to select responders to these treatments. There are several reasons why laboratory markers have been studied in IBD in the past decades: firstly, to gain an objective measurement of disease activity as symptoms are often subjective; secondly, to avoid invasive (endoscopic) procedures which are often a burden to the patient. An ideal marker should have many qualities. It should be easy and rapid to perform, cheap, and reproducible between patients and laboratories.

USEFULNESS OF CT COLONOGRAPHY IN PATIENTS WITH OCCLUSIVE COLORECTAL CANCER BEFORE METALLIC STENT PLACEMENT: A SINGLE ENTER EXPERIENCE

Up to 15% of patients with colorectal cancer (CRC) present with large bowel obstruction. Currently, computed tomography colonography (CTC) is regarded as a promising technique for complete evaluation of the proximal colon and simultaneous assessment of extraluminal status. Aim of this retrospective, observational study is to evaluate the feasibility of using CTC for preoperative examination of the proximal colon before metallic stent placement in patients with colon obstruction caused by CRC. Sixteen patients who demonstrated colonic obstruction caused by CRC, underwent CTC immediately after incomplete colonoscopy. Perpatient sensitivity of CTC for lesions 5 mm or larger in diameter in the colon proximal to the stent was 100% (95% CI: 0.4385-1). Per-patient specificity for lesions 5 mm and larger in the proximal colon was 92.3% (95% CI:0.6669-0.9863). CTC did not generate any false diagnosis of synchronous cancer. False positive findings at CTC did not result in a change in surgical plan for any patients. Although the small number of

Heat shock proteins and ulcerative colitis: The start of a new era?

http://dx.doi.org/10.1016/j.ajg.2015.04.002 1687-1979/ 2015 Arab Journal of Gastroenterology. Published by Elsevier Dear Sir, We read with great interest the article written by Abou El Azm and coworkers, published in the last issue of the Arab Journal of Gastroenterology [1]. In this article, the authors investigated the molecular expression of heat shock proteins (HSP) 70 and 90 in relation to the grades of inflammation and dysplasia in patients with ulcerative colitis (UC) before and after treatment. In this study, in agreement with other published studies [2–4], the authors not only found a potential role for HSP 70 and HSP 90 for assessment of the activity and prognosis of UC, but also such markers predicted the presence of dysplasia and differentiated it from reactive atypia [1]. HSP had been found not only a marker of active disease, thus considering UC as a ‘‘chaperonopathy by mistake’’, but also show a key role in the psychosocial setting in which inflammatory bowel diseases manifest themselves [5]. Furthermore, they could represent a new diagnostic tool to differentiate the different phenotypes of UC, thus allowing to tailor a targeted approach to better manage UC patients [6]. However, some unresolved issues still remain about the potential roles of HSP in both the acute and the longstanding disease. First, it should be interesting to assess the role of HSP in the infections associated to UC flares, like Clostridium difficile and Cytomegalovirus (CMV) infections. In fact, HSP could be investigated as a further marker of inflammation in case of severe and steroid-refractory disease; with regard to CMV infection, mucosal levels of HSP could differentiate when CMV plays a role of direct pathogen or when it represents merely a ‘‘silent bystander’’. Second, in longstanding UC, an integrated approach of colorectal cancer surveillance, by using the advanced endoscopic imaging together with mucosal markers, like HSP, could result in being markedly helpful, both to clinicians and pathologist. In fact, current guidelines recommend that image-enhanced endoscopy (IEE) may increase the yield of detection of dysplasia, thus representing a reasonable alternative to the random sampling of colon using standard white light [7]. The use of both IEE and new biomarkers, like HSP, predicting future occurrence of colonic neoplasia, could lead to a more centralised approach of UC patients, in which a ‘‘biomarker-based surveillance’’ might play a pivotal role.