Omitting duodenal biopsy in children with suspected celiac disease and extra-intestinal symptoms

The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines

Molecular biology, basic research and diagnosis of Hirschsprung's disease.

Das RET-Proto-Onkogen ist das zentrale für die Entstehung eines M. Hirschsprung verantwortliche Gen, wobei RET-Mutationen auch bei anderen pathologischen Läsionen vorkommen. Bei Hirschsprung-Patienten konnten eine Reihe verschiedener RET-Mutationen festgestellt werden. Besondere Aufmerksamkeit sollte denjenigen Patienten gewidmet werden, die Mutationen der Exone für die entscheidenden Zysteinreste aufweisen, welche für MEN2A prädisponieren. Bei diesen Patienten kann der M. Hirschsprung selten mit der Entwicklung neuroendokriner Tumoren, wie mit einem medullären Schilddrüsenkarzinom oder einer MEN2A assoziiert sein. Daher ist eine prophylaktische Thyreoidektomie dann ratsam, wenn eine tumorassoziierte RET-Mutation gefunden wurde. In MEN2A/Hirschsprung-Familien können die RET-Mutationsanalyse, Tumor-Screening und ggf. eine prohylaktische Thyreoidektomie wie bei MEN2A empfohlen werden. Der multigenetische Ursprung des M. Hirschsprung in Abwesenheit einer spezifischen Standard-Hirschsprung-Mutation macht eine genetische Routinediagnostik unmöglich

A Wolf in Sheeps Clothing:A Sporadic Juvenile Polyp of the Colon Harboring an Intramucosal Adenocarcinoma

We describe a solitary peduncolated polypoid lesion with a bilobated head in the transverse colon mucosa of a 51-year-old Caucasian man. Histologically, the lesion was consistent with juvenile polyp (JP), but showing a few dysplastic glands and a focus of intramucosal adenocarcinoma. This finding suggests that, at least in adults, even the sporadic JPs might carry an inherent potential for malignancy, which has so far only been pointed out for syndromic lesions. Additionally, we observed p53 overexpression in both the dysplastic lesions and in the invasive cells but not in the remaining epithelium. We can argue that p53 immunohistochemistry may be helpful in differentiating hyperplastic regenerative atypia of the epithelium, frequently found in JPs, from true dysplasia, a much more rare change in the sporadic JPs. </jats:p

The contribution of cell phenotype to the behavior of gastric cancer.

none8noSeveral histochemical studies suggest a role of tumor cell phenotype and related differentiation markers in the prognostic assessment of gastric cancer. Unfortunately, most studies have dealt with single or a few markers and have paid limited attention to their interplay with tumor histological types, which are potentially informative of prognosis. In this study, 292 invasive (T1b to T4) gastric cancers with prolonged follow-up and carefully analyzed histotype, inclusive of histotype-based grade, were investigated histochemically with a panel of 14 phenotypic markers known to be expressed in normal gut tissues and gastric cancer. Three of seven intestinal type markers investigated showed a trend for improved prognosis, one of which, CDX2, was stage independent. Three among gastric and pancreatobiliary duct markers (MUC1, MUC6, and pepsinogen II), predicted more severe prognosis stage independently, as did a combination of eight potentially informative (p &lt; 0.1 at univariable Cox analysis) markers. Cancers with predominantly intestinal phenotype had significantly better prognosis than those with predominantly gastric, mixed, or poorly defined phenotypes; among the latter, those with high lymphocyte response, with favorable outcome, were separated from anaplastic cancers, with ominous prognosis. At multivariable analysis, CDX2 and the eight marker combination proved to be stage- and grade-independent predictors. When individually considered, and with the exception of CDX2, the biomarkers investigated gave an appreciable, although moderate, contribution to the prognostic evaluation of gastric cancer. Combined analysis of all potentially informative markers gave more important information, highly additive to both stage and histotype-based grade.noneSolcia E;Klersy C;Vanoli A;Grillo F;Manca R;Tava F;Luinetti O;Fiocca RSolcia, E; Klersy, C; Vanoli, A; Grillo, Federica; Manca, R; Tava, F; Luinetti, O; Fiocca, Robert

Increased enterocyte apoptosis in inflamed areas of Crohn's disease

Because increased enterocyte apoptosis has been associated with the pathogenesis of several chronic inflammatory diseases, the aim of our study was to investigate epithelial cell death in Crohn's disease and the possible role of the Fas-Fas ligand system, E-cadherin, and matrix metalloproteinase-1 in modulating enterocyte apoptosis in this condition

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge

Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders including coeliac disease (CD) and Crohn&rsquo;s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear &beta;-catenin expression, as well as in prognosis. For these patients, high tumour-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear &beta;-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous &beta;-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review, we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC