Predicting Survival of Metastatic Clear Cell Renal Cell Cancer Treated with VEGFR-TKI-Based Sequential Therapy.

(1) Objective: To develop a clinically useful nomogram that may provide a more individualized and accurate estimation of cancer-specific survival (CSS) for patients with clear-cell (CC) metastatic renal cell carcinoma (mRCC) treated with nephrectomy and vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)-based sequential therapy. (2) Methods: A prospectively maintained database of 145 patients with mRCC treated between 2008 and 2018 was analyzed to predict the CSS of patients receiving sunitinib and second- and third-line therapies according to current standards of practice. A nomogram based on four independent clinical predictors (Eastern Cooperative Oncology Group status, International Metastatic RCC Database Consortium score, the Morphology, Attenuation, Size and Structure criteria and Response Evaluation Criteria in Solid Tumors response criteria) was calculated. The corresponding 1- to 10-year CSS probabilities were then determined from the nomogram. (3) Results: The median age was 60 years (95% CI 57.9-61.4). The disease was metastatic at diagnosis in 59 (40.7%), and 86 (59.3%) developed metastasis during follow-up. Patients were followed for a median 48 (IQR 72; 95% CI 56-75.7) months after first-line VEGFR-TKI initiation. The concordance probability estimator value for the nomogram is 0.778 ± 0.02 (mean ± SE). (4) Conclusions: A nomogram to predict CSS in patients with CC mRCC that incorporates patient status, clinical risk classification and response criteria to first-line VEGFR-TKI at 3 months is presented. This new tool may be useful to clinicians assessing the risk and prognosis of patients with mRCC.

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients.

Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20-30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.

SARS-CoV-2-Associated Obliterative Arteritis Causing Massive Testicular Infarction.

A 26-year-old man with symptomatic SARS-CoV-2 infection developed a sudden-onset acute testicular pain. The echo-doppler images showed massive testicular infarction, so orchiectomy was performed. On gross examination, the surgical specimen showed complete testicular necrosis and diffuse thickening of the testicular coverings. Under the microscope, a severe obliterative arteritis was evidenced. SARS-CoV-2 spike antibody was detected by immunohistochemistry in the arterial endothelium. Electron microscopy displayed intracytoplasmic spiky viral particles in endothelial cells. The patient was treated with corticoids and was asymptomatic at last contact.

[20 years urethroplasty experience. Retrospective review and outcomes.] / 20 años realizando uretroplastias. Revisión retrospectiva y resultados.

OBJECTIVE: To present the evolution in the diagnosis and treatment of urethral stricture, after performing 300 surgical procedures over urethral meatus,penile and bulbar urethra along 20 years, contrasting two surgical periods: from 1997-2006 to 2007-2016. MATERIAL AND METHODS: A retrospective review of495 medical records between 1997-2016 was conducted.All the patients treated with urethroplasty were included and those who under went internal urethrotomy,stents or dilatations plus those with strictures due to prostate cancer treatment or orthotopic neobladder were excluded. RESULTS: 300 patients were selected: 100 patients within the first period (1997-2006) and 200 within the second (2007-2016). The median follow-up was 36 months (range 12-60). In relation to the surgical techniques, among the most employed, four are outstanding so their results can be compared in both periods:termino-terminal urethroplasty, penile flap urethroplasty and the buccal mucosa in penile or bulbar urethroplasty.Other techniques were incorporated during the second period. The best outcomes were provided by end' to endurethroplasty with 90 and 92% success. Over the second period, buccal mucosa indications were consolidated with an increase use from 16% to 56%. Were considered as successful those patients that did not need any endoscopic procedure and reporting excellent urinary flow without low urinary tract symptoms. CONCLUSIONS: A trend towards an increased usage of open surgery vs urethrotomy is observed. Buccal mucosa graft has been consolidated as a reconstructive technique. End-to end urethroplasty seems to provide the best functional outcomes.

OBJETIVO: Mostrar la evolución en el diagnóstico y tratamiento de la estenosis uretral tras realizar 300 procedimientos quirúrgicos sobre meato uretral, uretra peneana y bulbar a lo largo de veinte años, comparando dos períodos: 1997-2006 y 2007-2016. MATERIAL Y METODOS: Llevamos a cabo una revisión de los historiales de 495 pacientes diagnosticados de estenosis de uretra entre 1997 y 2016. Incluímos todos aquellos que fueron sometidos a algún tipo de uretroplastia y fueron excluidos los tratados mediante uretrotomía interna, stents, dilataciones, y aquellos que presentaban estenosis a nivel de anastomosis, secundarias a tratamiento del cáncer de próstata o realización de vejigas ortotópicas. RESULTADOS: Seleccionamos 300 pacientes, 100 en el primer período (1997-2006) y 200 en el segundo (2007-2016). La media de seguimiento fue de 36 meses (12-60). Entre las técnicas empleadas destacamos cuatro de ellas para comparar los resultados en ambos períodos: Uretroplastia término terminal, Uretroplastia con mucosa oral en uretra peneana y bulbar y Uretroplastia con colgajo en uretra peneana. En el grupo 1,de 100 pacientes obtuvimos buenos resultados en el 83% y en el grupo 2, de 200 pacientes en el 81%.La técnica que mejores resultados proporcionó fue la término terminal con un 90 y 92% respectivamente. Enel segundo período se consolidó el uso de mucosa oral pasando de utilizarla en un 16% de los casos a un 56%. Consideramos buen resultado funcional aquellos pacientes que no precisaron ningún tipo de manipulación endoscópica o quirúrgica y manifestaron confort miccional con ausencia de síntomas obstructivos o irritativos. CONCLUSIONES: Aumenta el número de pacientes con estenosis de uretra tratados mediante cirugía abierta frente a la uretrotomía. Se consolida el empleo de la mucosa oral en todas sus variantes y se confirma que la uretroplastia término terminal es la técnica que proporciona mejores resultados.

Characterization of ferruginous cements related with weathering of slag in a temperate anthropogenic beachrock.

This work outlines a temperate latitude beachrock occurrence, which represents the legacy of heavy anthropogenic environmental disturbance. The units contain high amounts of slag and iron-rich wastes derived from metallurgical activities that attest the impact of the past industrial development on such coastal systems. The exposition of the anthropogenic wastes to weathering processes, such as the influence of marine aerosols and the chemical attack of acid gases like the SOx coming from the nearby urban-industrial atmosphere, gave rise to the formation of early diagenetic ferruginous cements. A new analytical methodology based on the combination of micro-Raman spectroscopy (MRS), Raman chemical imaging, SEM-EDS and the Structural and Chemical Analyzer (SCA, an emerging system that hyphenates micro-Raman and SEM-EDS), was applied for the first time to characterize the ferruginous cements. The MRS analyses revealed Fe2+/Fe3+ oxides and oxyhydroxides, CaCO3 polymorphs and less frequently silicates. The Fe mineral species detected were hydrated goethite, hematite, magnetite, magnesioferrite, lepidocrocite and goethite. Complementary Raman imaging, SEM-EDS and SCA analyses unraveled the preferential distribution of hydrated goethite. The identified iron mineral phases are weathering sub-products of hematite commonly derived from atmospheric/aqueous leaching processes triggered by the chemical attack of the acid gases. EDS showed the existence of other elements such as Si, Mg, Cl, Na, Al, K and sporadically S that indicated the importance of permeability, atmospheric deposition and the acid attack. Additionally, calcite and gypsum minerals also evidenced the action of meteoric waters, dry deposition processes or the attack of SOx acid gases. The presence of such compounds is modifying the cement stratigraphy and suggests that the dissolution of carbonates is currently taking place. Those facts influence the erosive susceptibility and the release of the anthropogenic materials trapped originally in the beachrocks, which could act as potential secondary sources of contaminants to the coastal environment.