Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations.

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.

Recomendaciones del grupo de trabajo de Uropatología de la Sociedad Española de Anatomía Patológica / Prostate pathology recommendations from the Uropathology working group of the Spanish Society of Pathology

Estas recomendaciones del grupo de trabajo de Uropatología de la Sociedad Española de Anatomía Patológica (SEAP) suponen un resumen del Libro blanco 2017. Se basan en recomendaciones del Colegio Americano de Patólogos, ISUP 2015, Clasificación OMS 2016 y TNM (AJCC) 2017. Incluyen recomendaciones de tallado, examen macroscópico y microscópico, así como de uso de inmunohistoquímica. Se detalla que el patrón Gleason 3 incluye glándulas hiperplásicas, atróficas y microquísticas, y el patrón 4 todas las glándulas cribiformes y glomeruloides. El Gleason en pieza de prostatectomía se modifica, y si existe un patrón terciario mayor que el primario y el secundario que comprende más del 5% del tumor, se incorpora como secundario. Tanto para biopsias como para prostatectomías, si el Gleason es 7, se recomienda informar el porcentaje de patrón 4. Se especifica el Gleason en variantes tumorales y situaciones especiales. Estas recomendaciones deben ser adaptadas según la práctica individual e institucional de acuerdo con los medios disponibles

These guidelines from the uropathology working group of the Spanish Society of Pathology (SEAP) are based on the European and ISUP 2015 recommendations and those of the College of American Pathologists, as well as the latest WHO 2016, TNM (AJCC) 2017 classifications. They include recommendations for specimen sampling, macro- and microscopic examination and immunohistochemistry. Gleason patterns are specified: Gleason pattern 3 includes hyperplastic, atrophic and microcystic glands, while pattern 4 includes all cribriform or glomeruloid glands. The Gleason score in prostatectomy specimens may change; if a tertiary pattern occurs in more than 5% of the tumour, it becomes a secondary pattern. In both biopsies and prostatectomy specimens, if the Gleason score is 7, the percentage of pattern 4 should be stated. Gleason scoring in tumor variants and special situations should also be specified. These recommendations should be adapted according to the resources available

Sclerosing Cholangitis Related to IgG4: Not Always a Curable Entity.

IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.

The present and future of prostate cancer urine biomarkers.

In order to successfully cure patients with prostate cancer (PCa), it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput "omic" techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field.

Prevalencia y repercusión clínica de la deficiencia de inmunoglobulina A en la enfermedad celíaca / Clinical relevance of immunoglobulin A deficiency in celiac disease

FUNDAMENTO: Determinar la prevalencia de la deficiencia de inmunoglobulina A (IgA) en pacientes diagnosticados de enfermedad celíaca, y establecer la influencia que tiene en la presentación y evolución de esta enfermedad. PACIENTES Y MÉTODO: Se han revisado los datos clínicos y biológicos de 47 pacientes diagnosticados clínica e histológicamente de enfermedad celíaca, en quienes se ha determinado la concentración de inmunoglobulinas séricas. RESULTADOS: En 5 pacientes los valores séricos de IgA fueron inferiores a 7 mg/dl (grupo con deficiencia de IgA) y en 42 fueron normales (grupo sin deficiencia de IgA). La edad y la relación varón/mujer fueron similares entre ambos grupos, al igual que la forma de presentación, las manifestaciones clínicas, los datos analíticos de malabsorción (anemia, hipocolesterolemia, hipoproteinemia e hipoprotrombinemia) y el patrón radiológico. Se detectó la existencia de bronquiectasias en dos de los 5 con deficiencia de IgA y en sólo uno de los 42 pacientes sin deficiencia de IgA (p < 0,05). Ningún paciente con deficiencia de IgA presentó complicaciones atribuibles a la enfermedad celíaca, mientras que 3 pacientes del grupo sin deficiencia de IgA desarrollaron linfoma intestinal (p = NS). CONCLUSIONES: La deficiencia de IgA se asocia con frecuencia a la enfermedad celíaca. Sin embargo, esta asociación no parece influir de forma significativa en la presentación y evolución clínicas ni interfiere con las pruebas de cribado para la enfermedad celíaca (AU)