A morphological and immunohistochemical study of human intestinal fibrogenesis during Crohn’s disease

Background. Several enteropathies are characterized by an intestinal fibrosis that may lead to stenosis and obstruction (1). The most frequent and severe intestinal fibrosis occurs in Crohn’s disease (CD) that is related to the abnormal accumulation of extracellular matrix (ECM) proteins. In experimental model TGF-β1/Smad3 signalling plays a major role in tissue fibrogenesis as a potent stimulus of ECM accumulation (2). Aim. To evaluate the potential role of the TGF-β1/Smads pathway in the pathogenesis of intestinal fibrosis in patients affected by CD. Methods.Human samples from terminal ileum were processed for histological (H&E, Masson, Pas) morphometric and immunohistochemical (IHC) analyses. For IHC studies TGF-β1, CTGF, collagen types I-III, Smad3, Smad7, PDGF, C-kit, α-SMA, GFAP and a neuronal cocktail (S100, antineurofilament, NSE) antibodies were used. Smooth muscle cells (SMC) were cultured (3) for morphofunctional and cell cycle analysis. Results. Histological and morphometrical evaluation of stenotic fragments revealed a significantly high degree of intestinal fibrosis with an increase in mucosa, submucosa and muscle layer thickness. Transmural inflammation was also present in stenotic lesions compared to normal tracts. SMC isolated from inflamed fragments presented a 18.7% ±5.9% lenght shortening and a 44.5%±2.9% inhibition in contractile response to acetylcholine. Furthermore, under inflammatory burst a shift from the G0/G1 to the S cell cycle phase was observed. IHC analysis showed an increase in TGF-β1,CTGF, collagen I-III, Smad3, PDGF, C-kit and α-SMA staining in stenotic lesions compared to pre-post stenotic intestinal tracts, whereas Smad7 was positive only in pre-post stenotic samples. IHC evaluation of GFAP and neuronal cocktail showed a reduction of immunoreactivity in stenotic lesions. Conclusions. The data demonstrate that the TGF-β1/Smads pathway may play a central role in the development and differentiation of mesenchymal cells and in sustaining fibrosis of intestinal tissues in CD. The results confirm those obtained previously in our experimental mice model. 1) Burke JP et al. Am J Gastro, 2007 2) Latella G. et al. Eur J Clin Invest, 2008 3) Tattoli I et al. Dig Liv Dis, 2004

Ultrasonographic detection and assessment of the severity of Crohn's disease recurrence after ileal resection

<p>Abstract</p> <p>Background</p> <p>Recurrence and severity of Crohn's disease mucosal lesions after "curative" ileal resection is assessed at endoscopy. Intramural lesions can be detected as increased wall thickness at Small Intestine Contrast Ultrasonography (SICUS).</p> <p>Aims. To assess after ileal resection whether: 1) SICUS detects recurrence of Crohn's disease lesions, 2) the intestinal wall thickness measured at the level of ileo-colonic anastomosis predicts the severity of endoscopic lesions, 3) the extension of intramural lesions of the neo-terminal ileum is useful for grading severity of the recurrence, 4) the combined measures of wall thickness of the ileo-colonic anastomosis and of the extension of intramural lesions at level of the neo-terminal ileum may predict the endoscopic Rutgeerts score</p> <p>Methods</p> <p>Fifty eight Crohn's disease patients (M 37, age range 19-75 yrs) were prospectively submitted at 6-12 months intervals after surgery to endoscopy and SICUS for a total of 111 observations.</p> <p>Results</p> <p>Six months or more after surgery wall thickness of ileo-colonic anastomosis > 3.5 mm identified 100% of patients with endoscopic lesions (p < 0.0001). ROC curve analysis, combining wall thickness of ileo-colonic anastomosis and the extension of intramural lesions of neo-terminal ileum, discriminated (0.95) patients with, from those without, endoscopic lesions. Performing two multiple logistic regression analyses only wall thickness of ileo-colonic anastomosis and extension of neo-terminal ileum intramural lesions were significantly associated with absence or presence of endoscopic lesions. An ordinal polychotomus logistic model, considering all investigated variables, confirmed that only SICUS variables were associated with endoscopic grading of severity.</p> <p>Conclusions</p> <p>In patients submitted to ileal resection for Crohn's disease non-invasive Small Intestine Contrast Ultrasonography 1) by assessing thickness of ileo-colonic anastomosis accurately detects initial, minimal Crohn's disease recurrence, and 2) by assessing both thickness of ileo-colonic anastomosis and extension of intramural lesions of neo-terminal ileum grades the severity of the post-surgical recurrence.</p

Allergic proctocolitis refractory to maternal hypoallergenic diet in exclusively breast-fed infants: a clinical observation

<p>Abstract</p> <p>Background</p> <p>Allergic proctocolitis (APC) in exclusively breast-fed infants is caused by food proteins, deriving from maternal diet, transferred through lactation. In most cases a maternal cow milk-free diet leads to a prompt resolution of rectal bleeding, while in some patients a multiple food allergy can occur. The aim of this study was to assess whether the atopy patch test (APT) could be helpful to identify this subgroup of patients requiring to discontinue breast-feeding due to polisensitization. Additionally, we assessed the efficacy of an amino acid-based formula (AAF) when multiple food allergy is suspected. amino acid-based formula</p> <p>Methods</p> <p>We have prospectively enrolled 14 exclusively breast-fed infants with APC refractory to maternal allergen avoidance. The diagnosis was confirmed by endoscopy with biopsies. Skin prick tests and serum specific IgE for common foods, together with APTs for common foods plus breast milk, were performed. After a 1 month therapy of an AAF all patients underwent a follow-up rectosigmoidoscopy.</p> <p>Results</p> <p>Prick tests and serum specific IgE were negative. APTs were positive in 100% infants, with a multiple positivity in 50%. Sensitization was found for breast milk in 100%, cow's milk (50%), soy (28%), egg (21%), rice (14%), wheat (7%). Follow-up rectosigmoidoscopy confirmed the remission of APC in all infants.</p> <p>Conclusions</p> <p>These data suggest that APT might become a useful tool to identify subgroups of infants with multiple gastrointestinal food allergy involving a delayed immunogenic mechanism, with the aim to avoid unnecessary maternal dietary restrictions before discontinuing breast-feeding.</p

Resezione endoscopica di un emangioma dello stomaco: a proposito di un caso clinico

Gli emangiomi gastrici rappresentano una infrequente varietà istologica di neoplasie benigne del tratto gastrointestinale. La diagnosi si avvale di diverse metodiche d’imaging ma la certezza si ottiene solo con l’esame istologico definitivo. La resezione per via endoscopica, rispettando alcuni criteri, rappresenta il trattamento di scelta per queste lesioni. Gli Autori presentano un caso di emangioma cavernoso della piccola curva gastrica, diagnosticato e trattato mediante approccio endoscopic

Microscopic colitis: a concise review

Microscopic colitis is an increasingly common cause of chronic watery diarrhoea, and often a causes of abdominal pain of unknown origins The increase of interest for this clinical entity is due to a misdiagnosis of any symptoms that have been frequently attributed to diarrhea-predominant irritable bowel syndrome, often for many years before diagnosis Presumably, most estimates of incidence and prevalence understate the true frequency of microscopic colitis for this reason The aim of this paper is to evaluate the importance of microscopic colitis as cause of chronic non bloody diarrhoea, on the basis of literature review These kind of colitis are characterized by normal colonic mucosa at endoscopy or barium enema but with increased inflammation in colonic biopsies Microscopic colitis consists of two main subtypes, collagenous colitis and lymphocyte colitis, distinguished by the presence of absence of a thickened subepithelial collagen band Several models of pathogenesis has been proposed but no convincing mechanism has been identified, although is difficult to characterize this clinical entity as an independent phenomenon or a simple manifestation or related factors active to induce microscopic changing in the colonic mucosa A rational approach to therapy does not exist and was conduct with several types of drugs after the exclusion of other causes, commonly characterized by this symptoms and the definitive histological assessment in the biopsies specimens In the majority of cases this condition tends to follow a self-limited course but potentially can assume the characteristics of relapsing course with the necessity to a chronic therapy Several long-term follow-up studies excluded a possible progression to neoplasm malignancies of microscopic colitis Clin Ter 2010, 161(4) 385-39

Laparoscopic-assisted resection of juvenile polyp of the jejunum in a 3-year-old girl

Sporadic juvenile polyp of the jejunum is exceedingly rare, reported only once in the English literature. We describe a 3-year-old girl with a long-lasting history of chronic iron deficiency anemia and a delayed diagnosis of jejunal polyp. The lesion was eventually discovered by ultrasonography and successfully resected using a laparoscopic-assisted transumbilical approach. (C) 2012 Elsevier Inc. All rights reserved

Is Cronkhite-Canada Syndrome necessarily a late-onset disease?

Cronkhite-Canada Syndrome is a non-inherited, non-congenital disease characterized by juvenile hamartomatous gastrointestinal polyps with a typically late onset. In the case described herein the disease was diagnosed in a 17-year-old male with type I diabetes and thalassaemia minor, in coincidence with severe symptomatic intestinal candidiasis. Following the disappearance of the mycosis and correction of the protein and electrolyte imbalance, the ectodermal abnormalities returned to normal and the patient remained asymptomatic during a 7-year follow-up period, despite proteinuria resulting from membranous glomerulopathy. The concept that Cronkhite-Canada Syndrome is a late-onset disease should probably be reconsidered as it may remain asymptomatic, and thus not diagnosed, for a long a time

Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in maintenance of remission in ulcerative colitis patients: 1-year follow-up study

Background: Mesalazine as maintenance therapy in ulcerative colitis is used worldwide and has been proven to be effective. However, the optimal dosage remains to be defined. Aim: To establish whether daily treatment with 2.4 g of oral mesalazine is more effective than 1.2 g in preventing disease relapse. Methods: A total of 156 patients with ulcerative colitis in remission were randomly treated for 1 year with 2.4 (n = 80) or 1.2 (n = 76) g/day of mesalazine. Activity of disease was assessed by periodical clinical, endoscopic and histological examinations. Results: After 12 months, 24 of 80 patients (30%) on 2.4 g and 20 of 76 patients (26%) on 1.2 g were still in remission (P = N.S.). Patients in 2.4 g group remained in remission for a longer time than those in 1.2 g group (P 3 relapses/year) was found to influence response to therapy. Conclusions: A daily dosage of 2.4 g of oral mesalazine seems to better at preventing and delaying relapses of ulcerative colitis than 1.2 g. The course of disease seems to be crucial in choosing the optimal dosage of mesalazine in a maintenance regimen