Our results suggest that mesothelial cells have an active role in the structural and functional alteration of the peritoneum during peritoneal dialysis. The findings suggest potential targets for the design of new dialysis solutions and markers for the monitoring of patients.

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Infección por virus C oculto en hepatopatías criptogenéticas Sr. Director: Desde que Brechot y colaboradores publicaron la primera serie de pacientes con Hepatitis B crónica sin hallazgo del antige-no de superficie en el suero (1) se ha venido hablando de virus B "oculto". Nosotros hemos colaborado en un trabajo de reciente publica-ción (2) en el que se ha estudiado una serie de 100 pacientes con alteración persistente de aminotransferasas y/o gamma-glutamil-transpeptidasa que no podía ser achacada a ninguna de las etiolo-gías habituales, incluyendo la negatividad de los marcadores virales (RNA-HVC, DNA-HVB) y en los que en cambio se encontró, en el 57%, por hibridación in situ, la presencia del RNA-HVC del genotipo lb en el tejido hepático y con una activi-dad necroinflamatoria y fibrótica superior a la histología de los pacientes sin RNA-HVC intrahepático. La reflexión, como clínico, que estos hallazgos implican me han hecho sumarizar las posibles consecuencias del mismo. Primero, en cuanto al diagnóstico, este hallazgo hecha por tie-rra la aseveración de que la ausencia en el plasma de marcadores del virus C (preferentemente el RNAHVC) elimina el diagnósti-co de Hepatopatía Crónica por virus C y, áun recogiendo los datos de mayor potencial necróticroinflamatorio y de fibrosis, desconocemos su evolución futura que precisará de seguimiento de estos pacientes. En cuanto a posibilidad de contagio, no tenemos aún el con-vencimiento de que el material genómico detectado sea infeccio-so, aunque con copias suficientes para identificar el genotipo 1b. Por otro lado el hecho de que, al menos en nuestra serie, los pacientes presenten elevaciones enzimáticas significativas, elimi-na el peligro de que puedan ser donantes en bancos de sangre, etc., pudiendo igualmente prevenirse posibles contagios parente-rales individuales. El hecho de no conocer aún la evolución específica de estos enfermos con virus C oculto, así como su pertenencia al genotipo Ib y que, únicamente por hibridación in situ de una nueva biopsia tras el tratamiento, pueda juzgarse de la eficacia del mismo, implican que, de momento, sólo deban emprenderse seguimien-tos y tratamientos muy controlados. A. Pérez Mota Servicio de Aparato Digestivo. Hospital Virgen de la Torre. Madrid 1. Bréchot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Bréchot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely "occult"?. Hepatology 2001; 34: 194-203. 2. El hepatocarcinoma es el tumor primario maligno hepático más frecuente. Una de sus manifestaciones clínicas es la produc-ción de síndromes paraneoplásicos. Entre los más frecuentes se encuentran la poliglobulia, la hipercalcemia, la hipoglucemia y la hiperlipidemia. De forma más rara, se han descrito reacciones leucemoides secundarias a hepatocarcinoma (1-3). El primer caso fue descrito por Ranke y cols. (1) en 1965. Tras realizar una bús-queda bibliográfica en Medline desde 1966-2002 existen escasos artículos publicados referentes a dicho tema y...

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Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in:The Journal of Pathology 231.4 (2013): 517-531 DOI: http://dx.doi.org/10.1002/path.4281 Copyright: © 2013 Pathological Society of Great Britain and IrelandEl acceso a la versión del editor puede requerir la suscripción del recurso Access to the published version may require subscription The authors disclose no potential conflicts of interest. integrin-dependent manner. Scanning electron microscopy imaging showed that the enhanced adhesion was mostly due to increased cell-cell interaction and not to a mere matrix exposure.Invasion assays suggested a reciprocal stimulation of the invasive capacity of tumor cells andMCs. Our results demonstrate that CAFs can derive from mesothelial cells during peritoneal metastasis. We suggest that MMT renders the peritoneum more receptive for tumor cell attachment/invasion and contributes to secondary tumor growth by promoting its vascularization.

Aspergillus fumigatus is responsible for a large percentage of nosocomial opportunistic fungal infections in immunocompromised hosts, especially during cytotoxic chemotherapy and after bone marrow transplantation, and is currently a major direct cause of death in leukemia patients. Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and is used by viral and bacterial pathogens to gain access to human DC. We report that DC-SIGN specifically interacts with clinical isolates of A. fumigatus. DC-SIGN-dependent binding of A. fumigatus conidia can be demonstrated with stable transfectants and monocyte-derived DC and is inhibited by anti-DC-SIGN Abs. Binding and internalization of A. fumigatus conidia correlates with DC-SIGN cell surface expression levels and is abolished in the presence of A. fumigatus-derived cell wall galactomannans. The clinical relevance of this interaction is emphasized by the presence of DC-SIGN in lung DC and alveolar macrophages, and further illustrated by the DC-SIGN-dependent attachment of A. fumigatus conidia to the cell membrane of IL-4-treated monocyte-derived macrophages. Our results suggest the involvement of DC-SIGN in the initial stages of pulmonary infection as well as in fungal spreading during invasive aspergillosis.

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls ( n = 15), non-CAPD uremic patients ( n = 17), uremic patients on CAPD ( n = 27) and non-renal patients with inguinal hernia ( n = 12). To study myofibroblastic conversion of mesothelial cells, alpha-smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and alpha-SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.

Peritoneal dissemination is the primary metastatic route of ovarian cancer (OvCa), and is often accompanied by the accumulation of ascitic fluid. The peritoneal cavity is lined by mesothelial cells (MCs), which can be converted into carcinoma‐associated fibroblasts (CAFs) through mesothelial‐to‐mesenchymal transition (MMT). Here, we demonstrate that MCs isolated from ascitic fluid (AFMCs) of OvCa patients with peritoneal implants also undergo MMT and promote subcutaneous tumour growth in mice. RNA sequencing of AFMCs revealed that MMT‐related pathways – including transforming growth factor (TGF)‐β signalling – are differentially regulated, and a gene signature was verified in peritoneal implants from OvCa patients. In a mouse model, pre‐induction of MMT resulted in increased peritoneal tumour growth, whereas interfering with the TGF‐β receptor reduced metastasis. MC‐derived CAFs showed activation of Smad‐dependent TGF‐β signalling, which was disrupted in OvCa cells, despite their elevated TGF‐β production. Accordingly, targeting Smad‐dependent signalling in the peritoneal pre‐metastatic niche in mice reduced tumour colonization, suggesting that Smad‐dependent MMT could be crucial in peritoneal carcinomatosis. Together, these results indicate that bidirectional communication between OvCa cells and MC‐derived CAFs, via TGF‐β‐mediated MMT, seems to be crucial to form a suitable metastatic niche. We suggest MMT as a possible target for therapeutic intervention and a potential source of biomarkers for improving OvCa diagnosis and/or prognosis. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.