F. Botti

The role of ultrasound elasticity imaging in predicting ileal fibrosis in Crohn's disease patients

Backgound:Bowel wall fibrosis is associated with a complicated disease behavior in patients with Crohns disease (CD). The quantitative assessment of fibrosis severity in CD-affected bowel can help clinical decision making. Our aim was to evaluate the feasibility, reliability, and reproducibility of ultrasound elasticity imaging (UEI) toward the assessment of ileal fibrosis in CD patients. Methods:Twenty-three consecutive patients with ileal or ileocolonic CD, elected for surgical resection of the terminal ileum, underwent bowel ultrasound and UEI. Twenty inflammatory CD patients without complications were enrolled as controls. Bowel wall stiffness was evaluated with UEI by means of color scale and quantitative strain ratio measurement. The severity of bowel wall fibrosis and inflammation were evaluated on histological sections by semiquantitative and quantitative image analysis and used as a reference standard. Results:The UEI strain ratio measurement was significantly correlated with the severity of bowel fibrosis at both semiquantitative and quantitative histological image analysis: it was characterized by an excellent discriminatory ability for severe bowel fibrosis (area under the receiver operating characteristic curve: 0.917; 95% confidence interval, 0.788–1.000). UEI strain ratio measurements were characterized by an excellent interrater agreement. At multivariate analysis, bowel wall fibrosis proved the only independent determinant of the strain ratio. The ileal strain ratio of inflammatory CD patients was significantly lower than in operated CD patients with severe fibrosis. Conclusions:UEI can be used to assess ileal fibrosis in CD patients.

IL-21 Is a Central Memory T Cell–Associated Cytokine That Inhibits the Generation of Pathogenic Th1/17 Effector Cells

IL-21 promotes Th17 differentiation, and Th17 cells that upregulate T-bet, IFN-γ, and GM-CSF drive experimental autoimmune diseases in mice. Anti–IL-21 treatment of autoimmune patients is therefore a therapeutic option, but the role of IL-21 in human T cell differentiation is incompletely understood. IL-21 was produced at high levels by human CD4+ central memory T cells, suggesting that it is associated with early T cell differentiation. Consistently, it was inhibited by forced expression of T-bet or RORC2, the lineage-defining transcription factors of Th1 and Th17 effector cells, respectively. Although IL-21 was efficiently induced by IL-12 in naive CD4+ T cells, it inhibited the generation of Th1 effector cells in a negative feedback loop. IL-21 was also induced by IL-6 and promoted Th17 differentiation, but it was not absolutely required. Importantly, however, IL-21 promoted IL-10 secretion but inhibited IFN-γ and GM-CSF production in developing Th17 cells, and consequently prevented the generation of polyfunctional Th1/17 effector cells. Moreover, in Th17 memory cells, IL-21 selectively inhibited T-bet upregulation and GM-CSF production. In summary, IL-21 is a central memory T cell–associated cytokine that promotes Th17 differentiation and IL-10 production, but inhibits the generation of potentially pathogenic Th1/17 effector cells. These findings shed new light on the role of IL-21 in T cell differentiation, and have relevant implications for anti–IL-21 therapy of autoimmune diseases.

Synchronous isolated splenic metastasis from colon carcinoma.

&NA; We report the first case known to us of a synchronous isolated splenic metastasis from colon carcinoma in a 52‐year‐old woman operated on splenectomy, left colectomy, and ileal resection. The patient died of diffuse carcinomatosis 1 year after the operation. Splenectomy for isolated splenic metastasis from colon carcinoma is justified, and serum tumor markers are useful to detect metastases early during the follow‐up, as in our report.

Confocal laser endomicroscopy for the detection of mucosal changes in ileal pouch after restorative proctocolectomy.

BACKGROUND Pouchitis and dysplasia may affect the reservoir after restorative proctocolectomy. AIMS To assess the suitability of confocal laser endomicroscopy for the in vivo diagnosis of mucosal changes in ileal pouch for ulcerative colitis and familial adenomatous polyposis. METHODS Standard endoscopy and endomicroscopy were performed in 18 pouches. Confocal images were scored for the presence of villous atrophy, inflammation, ulceration, colonic metaplasia and dysplasia. Targeted biopsies were taken. Endomicroscopic and histological findings were compared. RESULTS At standard endoscopy, the signs of pouchitis were recorded in 7/18 (38.9%) patients. At endomicroscopy, pathological features were found in 16/18 (88.9%), villous atrophy in 15/18 (83.3%), inflammation in 13/18 (72.2%), ulceration in 3/18 (16.7%), and colonic metaplasia in 12/18 (67.7%). No dysplasia was observed. At histology, abnormalities were present in 17/18 (94.4%): villous atrophy in 15/18 (83.3%), inflammation in 17/18 (94.4%), ulceration in 6/18 (33.3%), colonic metaplasia in 15/18 (83.3%). Morphological changes of the ileal pouch could be predicted with an accuracy of 94.4% (95% CI: 74.2-99.0). The k-value for intra- and interobserver agreement was 0.93 and 0.78, respectively. CONCLUSIONS Endomicroscopy may be helpful in the evaluation of morphologic changes in ileal pouch. The small size of the population sample requires further studies for the results to be confirmed.

Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol

BackgroundExperimental evidences suggest an increased collagen deposition in inflammatory bowel diseases (IBD). In particular, large amounts of collagen type I, III and V have been described and correlated to the development of intestinal fibrotic lesions. No information has been available until now about the possible increased collagen deposition far from the main target organ. In the hypothesis that chronic inflammation and increased collagen metabolism are reflected also in the systemic circulation, we aimed this study to evaluate the effects on left ventricular wall structure by assessing splancnic and systemic collagen metabolism (procollagen III assay), deposition (ultrasonic tissue characterization), and cardiac function (echocardiography) in patients with different long standing history of IBD, before and after surgery.MethodsThirty patients affected by active IBD, 15 with Crohn and 15 with Ulcerative Colitis, submitted to surgery will be enrolled in the study in a double blind fashion. They will be studied before the surgical operation and 6, 12 months after surgery. A control group of 15 healthy age and gender-matched subjects will also be studied. At each interval blood samples will be collected in order to assess the collagen metabolism; a transthoracic echocardiogram will be recorded for the subsequent determination of cardiac function and collagen deposition.DiscussionFrom this study protocol we expect additional information about the association between IBD and cardiovascular disorders; in particular to address the question if chronic inflammation, through the altered collagen metabolism, could affect left ventricular structure and function in a manner directly related to the estimated duration of the disease.

Surgery and diagnostic imaging in abdominal Crohn’s disease

Surgery is well-established option for the treatment of Crohn’s disease that is refractory to medical therapy and for complications of the disease, including strictures, fistulas, abscesses, bleeding that cannot be controlled endoscopically, and neoplastic degeneration. For a condition like Crohn’s disease, where medical management is the rule, other indications for surgery are considered controversial, because the therapeutic effects of surgery are limited to the resolution of complications and the rate of recurrence is high, especially at sites of the surgical anastomosis. In the authors’ opinion, however, surgery should not be considered a last-resort treatment: in a variety of situations, it should be regarded as an appropriate solution for managing this disease. Based on a review of the literature and their own experience, the authors examine some of the possibilities for surgical interventions in Crohn’s disease and the roles played in these cases by diagnostic imaging modalities.RiassuntoLa chirurgia è un’opzione terapeutica consolidata per il trattamento della malattia di Crohn refrattaria alla terapia medica e per le complicanze legate a tale patologia quali stenosi, fistole, ascessi, sanguinamento non trattabile endoscopicamente, oltre che per i casi di degenerazione neoplastica. Per condizioni come la malattia di Crohn nelle quali il trattamento medico ha un ruolo primario, altre indicazioni per la chirurgia sono controverse, poiché i suoi effetti terapeutici sono limitati alla risoluzione delle complicanze, e la frequenza di recidive è alta, soprattutto a livello dell’anastomosi. Secondo l’opinione degli autori, tuttavia, la chirurgia non deve essere considerata come ultima opzione di trattamento: in diverse situazioni dovrebbe essere ritenuta come una soluzione adeguata nel trattamento multidisciplinare della patologia. Basandosi sulla revisione della letteratura corrente e sulla propria esperienza, gli autori hanno esaminato alcune possibilità di intervento chirurgico nella malattia di Crohn ed il ruolo che svolgono in queste condizioni le tecniche di imaging.

Adalimumab is safe and effective in re-inducing clinical remission after post-surgical relapse of Crohn's disease: A case report

Abstract We present the case of a 36-year-old patient with ileo-colonic stricturing Crohns disease that recurred after surgery, did not respond to maximal medical therapy and was only partially responsive to treatment with adalimumab administered subcutaneously. The patient underwent surgery following an episode of intestinal obstruction, revealing chronic, adhesive peritonitis, with the intestinal loops fixed strongly together, and a fibrotic stricture of the pre-anastomotic ileum. The numerous adhesions were carefully separated and the stenotic tract of ileum was resected. Following the resection the patient had an early clinical relapse, which was documented by abdominal ultrasound. The patient was, therefore, treated again with adalimumab: the new cycle of treatment achieved clinical and ultrasonographic remission of the disease. Despite the previous treatment, no side-effects occurred.

Previous colonic resection is a risk factor for surgical relapse in Crohn’s disease

BACKGROUND Despite the improvement of medical therapies, nearly half of patients with Crohns disease require surgery within 10 years after diagnosis. However, intestinal resection is not curative and recurrence may occur. AIMS To evaluate post-surgical outcomes for patients with Crohns disease in a large monocentric cohort, and to identify variables associated with clinical and surgical relapse. METHODS Patients with Crohns disease who had surgery for ileal and colonic Crohns disease between 2004 and 2016 and on at least one-year follow-up following surgery were included. RESULTS One hundred ninety-three patients were included in the study. Crohns disease recurrence concerned 53% of patients after a median 56-month (6-158) follow-up and 29% of patients required a second surgical intervention. At logistic regression analysis, active smoking and young age at diagnosis were identified as independent risk factor for post-surgical relapse (p = 0.01), while colonic or ileocolonic resection was recognized as a risk factor for surgical Crohns disease relapse (p = 0.003). CONCLUSIONS Post-surgery recurrence is frequent for patients with Crohns disease. Active smoking and young age at diagnosis are risk factors for Crohns disease recurrence. As compared with patients undergoing small-bowel surgery, patients with colonic resection are proner to relapse requiring a second surgical intervention.