Diagnosis and treatment of coeliac disease

It is now clearly established that coeliac disease is much more common than originally considered. While in the past it was taught that coeliac disease was mainly a disease of children, it is clear now that it may be diagnosed at any age. The clinical presentation of adolescents and adults is, however, less typical. Recent evidence suggests that coeliac disease is a multi-organ disease. The diagnostic techniques involving histology and serologic testing have been improved and the involvement of environmental and genetic factors in the pathogenesis of this immune disorder has been clarified, although the pathogenesis is not yet completely understood. Complications are now better identified, and new treatment strategies are under consideration

Treatment of a mixed acinar-endocrine carcinoma with uptake on 68Gallium-DOTATOC positron emission tomography-computed tomography : a case report

The case of a 35-year old female patient with a diagnosis of metastatic mixed acinar-endocrine carcinoma (MAEC) is investigated in the present study. The patient was believed to have a well-differentiated neuroendocrine tumor (NET) with a high Ki-67 index and uptake on (68)Gallium-DOTATOC positron emission tomography-computed tomography for 9 years, and was treated accordingly. The patient had long lasting disease control by treatment with sunitinib, and a response was observed in numerous lesions with peptide receptor radionuclide therapy (PRRT). Following treatment for metastatic disease for >4 years, liver transplantation was performed, as an exception to normal recommendations, at the time of progression of a centrally located liver lesion inducing obstructive jaundice. Following transplantation, the diagnosis of a Grade 3 NET, as defined by the WHO 2010 classification, was challenged and changed to MAEC. MAEC is a rare type of tumor of the pancreas, exhibiting endocrine and acinar differentiation. It is difficult to diagnose, often being misidentified as acinar cell carcinoma or predominantly as neuroendocrine neoplasms. Immunohistochemical labelling provides the only evidence for the dual differentiation of neuroendocrine (synaptophysin and chromogranin) and acinar (lipase, trypsin and chymotrypsin) cell markers. Studies investigating MAECs with a clear histopathological diagnosis are scarce, in addition to evidence of disease behaviour and treatment options. It is generally agreed that surgery is the primary treatment in patients with resectable tumors. The responses to sunitinib and PRRT suggested that treatments considered or developed for NETs may be beneficial in MAEC cases

Discrepancy between the in vitro and in vivo effects of murine mesenchymal stem cells on T-cell proliferation and collagen-induced arthritis

INTRODUCTION: The goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA). An additional aim is to investigate the role of interferon-gamma (IFN-gamma) in these processes. METHODS: MSC were isolated from bone marrow of DBA/1 wild type and IFN-gamma receptor knock-out (IFN-gammaR KO) mice and expanded in vitro. Proliferation of anti-CD3-stimulated CD4+ T cells in the presence or absence of MSC was evaluated by thymidine incorporation. CIA was induced in DBA/1 mice and animals were treated with MSC by intravenous or intraperitoneal injections of wild type or IFN-gammaR KO MSC. RESULTS: Purity of enriched MSC cultures was evaluated by flow cytometry and their ability to differentiate into osteoblasts and adipocytes. In vitro, wild type MSC dose-dependently suppressed anti-CD3-induced T cell proliferation whereas IFN-gammaR KO MSC had a significantly lower inhibitory potential. A role for inducible nitric oxide (iNOS), programmed death ligand-1 (PD-L1) and prostaglandin E2 (PGE2), but not indoleamine 2,3-dioxigenase (IDO), in the T cell inhibition was demonstrated. In vivo, neither wild type nor IFN-gammaR KO MSC were able to reduce the severity of CIA or the humoral or cellular immune response toward collagen type II. CONCLUSIONS: Whereas MSC inhibit anti-CD3-induced proliferation of T cells in vitro, an effect partially mediated by IFN-gamma, MSC do not influence in vivo T cell proliferation nor the disease course of CIA. Thus there is a clear discrepancy between the in vitro and in vivo effects of MSC on T cell proliferation and CIA.status: publishe

Genetic diversity and population structure of the Eurosian otte (Lutra lutra) in France

During the last century, the Eurasian otter (Lutra lutra) suffered a dramatic decline in Europe. In France, the same pattern of sharp decline was observed with local extinctions in many regions. Before the recolonisation process, two main populations still remained along the Atlantic coast and in the Massif Central. To investigate the impact of this decline on the genetic diversity and structure of the French otter population, tissue samples of 144 otter carcasses from road kills that were found during 1992–2011 along the Atlantic coast and in the Massif Central were used. They were analysed using 10 microsatellites loci. Observed (Ho = 0.64) and expected heterozygosity (He = 0.62) were moderate, but consistent with results found in other European populations. The bottleneck test showed an excess of heterozygotes, providing evidence of a recent decline. There was evidence for weak but significant allelic frequencies divergence between otters from the Atlantic coast and those from the Massif Central (Fst=0.040, p<0.05), probably resulting from their isolation prior to the recolonisation process. As the French otter population has been expanding for several years, genetic intermixing is now occurring. Although this expansion has not yet genetically homogenised all populations, this is may be a matter a time

Surveillance recommendations for patients with Lynch syndrome and FAP : a monocentric study

Background and study aims : The most important causes of hereditary colorectal cancer are Lynch syndrome (LS) and the adenomatous poly-posis syndromes (familial adenomatous polyposis syndrome or FAP, attenuated FAP or AFAP and MUTYH associated polyposis syndrome or MAP). The aim of this study was to investigate whether all patients with a hereditary syndrome within one center receive uniform advice regarding surveillance and treatment. Patients and methods : A retrospective analysis was performed of all electronic patient health records of patients with LS, FAP, AFAP and NIAP who received genetic counselling or were followed by a health care specialist at the l'niversity Ilospital in Ghent. Results : Data from 122 patients were collected. For all patients, recommendations from the medical genetics department were highly consistent. Adherence to their recommendations was good within the center for the management of colon polyps. There was a lack of consistency in the screening and surveillance advice for other tumors in departments other than gastroenterology. Only 33 patients had systematic follow-up consultations to check results and organize surveillance. Conclusion : Previously, small studies have suggested that patients with hereditary gastrointestinal cancer syndromes infrequently have surveillance as specified in the guidelines. This study shows almost uniform recommendations and good adherence for surveillance of the colon, but incomplete or contradictory advice for surveillance of other organs. The need for an integrated approach from a multidisciplinary team will only increase in the future, because more Families with hereditary cancer are likely to be found due to the increased use of next generation sequencing in cancer diagnostics