Identification of Novel/Rare EWSR1 Fusion Partners in Undifferentiated Mesenchymal Neoplasms.

Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of EWSR1 translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving EWSR1 in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3' partners, NR4A2 and RORB, which have not been previously reported. NR4A2 may functionally replace NR4A3, the usual 3' partner in extraskeletal myxoid chondrosarcoma. The third GF, EWSR1::BEND2, has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing EWSR1 fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting.

Cigarette smoke-induced oxidative stress in skeletal muscles of mice.

Cigarette smoke (CS)-induced oxidative stress may cause muscle alterations in chronic conditions such as chronic obstructive pulmonary disease (COPD). We sought to explore in AKR/J mice exposed to CS for 6 months and in control animals, levels of protein oxidation, oxidized proteins (immunoblotting, proteomics) and antioxidant mechanisms in both respiratory and limb muscles, body weight modifications, systemic inflammation, and lung structure. Compared to control mice, CS-exposed animals exhibited a reduction in body weight gain at 3 months and thereafter, showed lung emphysema, and exhibited increased oxidative stress levels in their diaphragms and gastrocnemius at 6 months. Proteins involved in glycolysis, ATP production and distribution, carbon dioxide hydration, and muscle contraction were carbonylated in respiratory and limb muscles. Blood tumor necrosis factor (TNF)-alpha levels were significantly greater in CS-exposed mice than in control animals. In AKR/J mice, chronic exposure to CS induces lung emphysema concomitantly with greater oxidative modifications on muscle proteins in both respiratory and limb muscles, and systemic inflammation.

Results of adrenal surgery. Data of a Spanish National Survey.

PURPOSE: Given the availability of laparoscopy and the rising detection of incidentalomas, indications for adrenalectomy may be changing. The Endocrine Surgery Section of the Spanish Association of Surgeons designed a survey to assess its indications, techniques, and results in Spanish Surgical Departments. METHODS: Collected data included hospital and department type, yearly hospital volume of procedures; location studies and preoperative preparation performed, indications, surgical approach and instruments used, and results in terms of morbidity and overall hospital stay. The analysis included a comparison between results of high- or low-volume centers and surgeons, using the Student's t test for quantitative and chi-square test for qualitative variables. Level of significance was set at 0.05. RESULTS: Nineteen centers returned the questionnaire, including 155 adrenalectomies performed in 2008. Most frequent indications were pheochromocytoma (23.2%), aldosteronoma (16.7%), incidentaloma (12.2%), metastasis (10.3%), Cushing adenoma (9.6%), and carcinoma (3.8%). Laparoscopy was performed in 83.9% of cases (9.4% required conversion to laparotomy). Four patients required urgent reoperation. Average hospital stay: 4.6 days (3.3 days after laparoscopy, 7 days after laparotomy). High-volume centers had a greater proportion of laparoscopically treated cases (p = 0.008), more malignant lesions treated (p = 0.03), a shorter overall stay (p < 0.0001), and a shorter stay after laparotomic adrenalectomy (p = 0.01). High-volume surgeons had similar results, and less in-hospital morbidity (p = 0.02). CONCLUSIONS: In Spain, adrenalectomy is performed in hospitals of varying complexity. Laparoscopic approach is the rule, with good results in terms of morbidity and stay. High-volume centers and surgeons had best results in terms of use of minimally invasive surgery and hospital stay.

El factor de crecimiento de hígado mejora la fibrosis pulmonar inducida tras la administración de cadmio en ratas / Liver growth factor improves pulmonary fibrosis secondary to cadmium administration in mice

IntroducciónEl liver growth factor (LGF, ‘factor de crecimiento de hígado’) es un mitógeno con actividad regeneradora y antifibrótica con actividad incluso en localizaciones extrahepáticas. En este trabajo se administró LGF en un modelo de fibrosis pulmonar inducido con cloruro de cadmio (CdCl2) para estudiar su capacidad antifibrótica.MétodosSe instilaron 42 ratas Wistar macho con 0,5ml/rata de CdCl2 al 0,025% (n=21) o de salino (n=21). Transcurridos 35 días y una vez establecida la lesión se realizó el tratamiento con LGF y posteriormente el análisis de los parámetros funcionales —capacidad inspiratoria (CI), complianza pulmonar (CL), capacidad vital forzada (CVF) y flujo espiratorio forzado al 75% (FEF75%)—, morfometría —área interna alveolar y distancia media entre paredes alveolares— y contenido en colágeno y elastina.ResultadosLa fibrosis pulmonar originada mediante CdCl2 se caracterizó por un marcado descenso de la función pulmonar en comparación con los controles. Se redujó un 28% la CI, un 38% la CL, un 31% la CVF y un 54% la FEF75%, descenso que se revirtió parcialmente tras la inyección de LGF —el 18% en CI, el 27% en CL, el 19% en CVF y el 35% en FEF75&%#x02014;. Además, se observó un incremento en la cantidad de colágeno y elastina del 165 y el 76%, respectivamente, en las ratas del grupo CdCl2 frente a un 110 y un 34% tras la inyección de LGF.ConclusionesEstos datos demuestran que el LGF mejora la función pulmonar y revierte parcialmente el incremento de las proteínas de matriz pulmonar producido por la instilación con CdCl2(AU)

IntroductionLiver growth factor (LGF) is a liver mitogen with regenerating and anti-fibrotic activity even at extrahepatic sites. We used LGF in a lung fibrosis model induced by cadmium chloride (CdCl2), to study its antifibrotic capacity.MethodsForty-two male Wistar rats were administered a single dose of 0.5ml/rat of CdCl2 0.025% (n=21) or the same volume of saline (control group, n=21). After 35 days, once a lesion was established, we started a 3 week treatment with LGF, after which we determined lung function —inspiratory capacity (IC), lung compliance (LC), forced vital capacity (FVC) and expiratory flow at 75% (FEF75%)—, lung morphometry —alveolar internal area (AIA), mean linear intersection (LM)—, and collagen (both by Sirius red and hydroxyproline residues) and elastin contents.ResultsPulmonary fibrosis in CdCl2 rats was characterized by a marked decrease in pulmonary function with respect to healthy controls —reductions of 28% in IC, 38% in CL, 31% in FVC, and 54% in FEF75&%#x02014; which was partially recovered after LGF injection —18% IC, 27% CL, 19% FVC and 35% FEF75&%#x02014;; increase in collagen and elastin contents —165% and 76%, respectively, in CdCl2 rats, versus 110% and 34% after LGF injection—; and increases in AIA and LM, partially reverted by LGF. Conclusions: Together, these data seem to demonstrate that LGF is able to improve lung function and partially reverts the increase in lung matrix proteins produced by CdCl2 instillation(AU)

[Liver growth factor improves pulmonary fibrosis secondary to cadmium administration in rats]. / El factor de crecimiento de hígado mejora la fibrosis pulmonar inducida tras la administración de cadmio en ratas.

INTRODUCTION: Liver growth factor (LGF) is a liver mitogen with regenerating and anti-fibrotic activity even at extrahepatic sites. We used LGF in a lung fibrosis model induced by cadmium chloride (CdCl(2)), to study its antifibrotic capacity. METHODS: Forty-two male Wistar rats were administered a single dose of 0.5ml/rat of CdCl2 0.025% (n=21) or the same volume of saline (control group, n=21). After 35 days, once a lesion was established, we started a 3 week treatment with LGF, after which we determined lung function--inspiratory capacity (IC), lung compliance (LC), forced vital capacity (FVC) and expiratory flow at 75% (FEF75%)-, lung morphometry--alveolar internal area (AIA), mean linear intersection (LM)-, and collagen (both by Sirius red and hydroxyproline residues) and elastin contents. RESULTS: Pulmonary fibrosis in CdCl(2) rats was characterized by a marked decrease in pulmonary function with respect to healthy controls -reductions of 28% in IC, 38% in CL, 31% in FVC, and 54% in FEF75%- which was partially recovered after LGF injection -18% IC, 27% CL, 19% FVC and 35% FEF75%-; increase in collagen and elastin contents -165% and 76%, respectively, in CdCl2 rats, versus 110% and 34% after LGF injection-; and increases in AIA and LM, partially reverted by LGF. CONCLUSIONS: Together, these data seem to demonstrate that LGF is able to improve lung function and partially reverts the increase in lung matrix proteins produced by CdCl(2) instillation.