A pSMAD/CDX2 Complex Is Essential for the Intestinalization of Epithelial Metaplasia

The molecular mechanisms leading to epithelial metaplasias are poorly understood. Barrett's esophagus is a premalignant metaplastic change of the esophageal epithelium into columnar epithelium, occurring in patients suffering from gastroesophageal reflux disease. Mechanisms behind the development of the intestinal subtype, which is associated with the highest cancer risk, are unclear. In humans, it has been suggested that a nonspecialized columnar metaplasia precedes the development of intestinal metaplasia. Here, we propose that a complex made up of at least two factors needs to be activated simultaneously to drive the expression of intestinal type of genes. Using unique animal models and robust in vitro assays, we show that the nonspecialized columnar metaplasia is a precursor of intestinal metaplasia and that pSMAD/CDX2 interaction is essential for the switch toward an intestinal phenotype

Lectin staining shows no evidence of involvement of glycocalyx/mucous layer carbohydrate structures in development of celiac disease

The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA) staining for Gal-β(1,3)-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates

Primary Carcinoma of the Gallbladder

Carcinoma of the gallbladder is a relatively rare malignancy which is difficult to diagnose. The advent of improved imaging methods and the expansion of interventional radiology however, combined with advances in surgical technique, has produced a change in attitude towards this tumour. The available world literature since 1960 has been reviewed and is presented in this article. However, whilst the outlook for diagnosis and treatment is improving, clearly the association with cholelithiasis (between 45% and 100%), is a cause for concern particularly with the advent of treatments (lithotripsy, percutaneous gallstone extraction) which leave gall bladder mucosa and residual fragments of stone in situ

Histological hallmarks of mucosal healing in inflammatory bowel diseases in the era of monoclonal antibodies therapy: New insights and perspectives

Background: Chronic inflammatory bowel diseases (IBDs) are gaining increasing attention, both because they can severely reduce the quantity and quality of life, and because the advent of monoclonal antibodies has profoundly changed the natural history of these diseases. In recent years, the concept of mucosal healing has assumed a certain importance, and there are more and more clinical and pharmacological trials that consider this parameter among their endpoints, so much so that it may soon be included among the desirable clinical outcomes of patients with IBD. Methods: We performed a literature review of the Pubmed, Medline, and Web of Science (WoS) databases. Results: We selected 88 articles and then removed 6 duplicates; the final sample after accurate application of the inclusion criteria numbered 73 articles, with a level of evidence rating of three or four, according to Oxfords Evidence-based medicine. Our aim was to study the histological impact of monoclonal antibody therapies on mucosal healing, taking into consideration the few studies present in the literature. To perform this review, we compared studies that examined patients with Crohn’s disease (CD) and/or ulcerative colitis (UC) undergoing monoclonal therapy versus patients undergoing other non-biological therapies (PICO statements). Conclusions: We try to delineate how monoclonal antibodies have changed the natural history of IBD, acting at the microscopic level, and we believe that a careful analysis of the histopathology and the definition of the objective criteria for “Mucosa Healing” should enable this concept to be included among the clinical endpoints of patients affected by IBD, thus contributing to a better therapeutic management of these patients