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Background One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, even though they are not expressed by the tumor cells. We have generated a CAR specific for the splice variant extra domain A (EDA) of fibronectin, which is highly expressed in the tumor stroma of many types of tumors but not in healthy tissues. Methods EDA expression was explored in RNA-seq data from different human tumor types and by immunohistochemistry in paraffin-embedded tumor biopsies. Murine and human anti-EDA CAR-T cells were prepared using recombinant retro/lentiviruses, respectively. The functionality of EDA CAR-T cells was measured in vitro in response to antigen stimulation. The antitumor activity of EDA CAR-T cells was measured in vivo in C57BL/6 mice challenged with PM299L-EDA hepatocarcinoma cell line, in 129Sv mice-bearing F9 teratocarcinoma and in NSG mice injected with the human hepatocarcinoma cell line PLC. Results EDA CAR-T cells recognized and killed EDA-expressing tumor cell lines in vitro and rejected EDA-expressing tumors in immunocompetent mice. Notably, EDA CAR-T cells showed an antitumor effect in mice injected with EDA-negative tumor cells lines when the tumor stroma or the basement membrane of tumor endothelial cells express EDA. Thus, EDA CAR-T administration delayed tumor growth in immunocompetent 129Sv mice challenged with teratocarcinoma cell line F9. EDA CAR-T treatment exerted an antiangiogenic effect and significantly reduced gene signatures associated with epithelial-mesenchymal transition, collagen synthesis, extracellular matrix organization as well as IL-6-STAT5 and KRAS pathways. Importantly, the human version of EDA CAR, that includes the human 41BB and CD3 zeta endodomains, exerted strong antitumor activity in NSG mice challenged with the human hepatocarcinoma cell line PLC, which expresses EDA in the tumor stroma and the endothelial vasculature. EDA CAR-T cells exhibited a tropism for EDA-expressing tumor tissue and no toxicity was observed in tumor bearing or in healthy mice. Conclusions These results suggest that targeting the tumor-specific fibronectin splice variant EDA with CAR-T cells is feasible and offers a therapeutic option that is applicable to different types of cancer.

Introduction: Priapism is a prolonged erection that lasts longer than four hours. It is a rarepathology in the pediatric population, with an estimation of 0.3-1.5 per 100,000 children peryear. The diagnostic sequence includes clinical history, physical examination and penile Dopplerultrasound (PDUS). Puncture of corpora cavernosa is not always necessary to establish thedifferential diagnosis between high-flow and low-flow priapism. The treatment of choice inpediatric age is not well defined. Patients and methods: Multicentric, retrospective and descriptive study including patientsunder 14 years with high-flow priapism between 2010 and 2020. Literature review. Results: A total of seven patients were diagnosed with high-flow priapism. None of them required puncture of the corpora cavernosa. Patients were treated with a conservative management, two patients required superselective arterial embolization due to persistent symptoms. Conclusions: High-flow priapism is a very rare entity in pediatric age; therefore, knowing theproper diagnosis and management is crucial. Currently, penile doppler ultrasound is enough fordiagnosis in most cases and allows obviating the use of blood gas analysis. Children should beinitially treated with a conservative management, reserving embolization for refractory cases. (c) 2021 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.

After transvaginal adjustable tape, approximately 15% of patients still suffer incontinence, and voiding dysfunction is present in a relatively important number of patients. Transvaginal adjustable tape (TVA) permits postoperative readjustment of tension, suggesting that better results could be obtained. Sixty-four incontinent women received TVA. Patients were monitored 1, 6, and 12 months post-surgery and annually thereafter by medical history, cough stress test, flowmetry and post-void residual test (PVR), incontinence quality of life, International Consultation on Incontinence Questionnaire-Short Form, and Patient Global Impressions of Improvement (PGI-I) questionnaires. After adjustment, all patients rendered continent, and none had PVR. On no occasion was vesical catheterization or uretholysis necessary. Mean follow-up was 40+/-12.9 months. Objective and subjective cure rate were 94% and 56%, respectively. Q(max) was 22.3+/-9.9 ml/s. The PGI-I questionnaire showed 94% of patients to be better or very much better than before. Our data suggest that with TVA tape, better results can be obtained, furthermore, without increasing surgical complications.

Vaccination strategies based on the in vivo targeting of Ags to dendritic cells (DCs) are needed to improve the induction of specific T cell immunity against tumors and infectious agents. In this study, we have used a recombinant protein encompassing the extra domain A from fibronectin (EDA), an endogenous ligand for TLR4, to deliver Ags to TLR4-expressing DC. The purified EDA protein was shown to bind to TLR4-expressing HEK293 cells and to activate the TLR4 signaling pathway. EDA also stimulated the production by DC of proinflammatory cytokines such as IL-12 or TNF-alpha and induced their maturation in vitro and in vivo. A fusion protein between EDA and a cytotoxic T cell epitope from OVA efficiently presented this epitope to specific T cells and induced the in vivo activation of a strong and specific CTL response. Moreover, a fusion protein containing EDA and the full OVA also improved OVA presentation by DC and induced CTL responses in vivo. These EDA recombinant proteins protected mice from a challenge with tumor cells expressing OVA. These results strongly suggest that the fibronectin extra domain A may serve as a suitable Ag carrier for the development of antiviral or antitumoral vaccines.

Objetivos: Valoración de una nueva malla de incontinencia (TVA/TOA) que permite postoperatoriamente ajustar la tensión dada en quirófano. Pacientes y Métodos: 62 pacientes tratados con la malla TVA, seguimiento medio de 14 meses (DS 7,8, rango 6-38). En 33 pacientes (53%) se añadió corrección de algún prolapso. La valoración se ha realizado mediante historia clínica, exploración con vejiga llena con 250 cc de suero salino, flujometría y residuo. 40 pacientes han rellenado 4 cuestionarios de calidad de vida. (QoL; ICIQ-SF; PGI-S y PGI-I). Resultados: 42 pacientes eran continentes en la valoración post-operatoria. De estos, fue necesario disminuir la tensión en 7 (11%) por obstrucción urinaria (flujo

Objetivos: Describir los principales factores pronósticos del carcinoma renal y estudiar su relación con la supervivencia especifica. Recoger datos demográficos, clínicos, diagnósticos y terapéuticos de los pacientes. Material y métodos: Se revisaron 202 casos de carcinomas renales operados entre 1988-2003. Las variables valoradas respecto al paciente fueron: edad, sexo y presentación clínica. Se investigó la importancia del incidentaloma. Con respecto al tumor se valoró: estadio TNM, grado histológico, tamaño y afectación venosa. Con respecto al tratamiento: principales vías de abordaje y técnicas quirúrgicas y terapia adyuvante inmunoterápica. Resultados: Un 60% de los pacientes presentó enfermedad organoconfinada, un 10% afectación nodal y un 7% enfermedad metastásica. Un 42% se presentaron incidentalmente, con una significativa mejor supervivencia respecto a tumores sintomáticos. Un 42% de los pacientes pN+ presentaron metástasis a distancia al diagnóstico y un tercio las desarrollaron durante el seguimiento. La supervivencia de los pacientes metastásicos sin tratamiento adyuvante fue inferior al año, mientras que un 20% de los tratados con inmunoterapia permanecían vivos a los 2 años. Conclusiones: El carcinoma renal es un tumor con alta mortalidad, fundamentalmente en sus estadios más avanzados (pN+ o pM+). Pese a las nuevas modalidades de tratamiento, no se ha logrado mejorar sustancialmente la supervivencia. Objectives: To describe renal cell carcinoma prognostic factors and set up the relationship with survival rates in this neoplasm. Likewise we show epidemiologic, clinical, diagnosis and therapeutic facts. Material and method: We review 202 patients underwent surgical treatment for renal cell carcinoma and the following features were recorded: gender, age and presenting symptoms, especially incidentally discovered tumors; tumor-related factors like TNM tumor stage, tumor grade and venous involvement; therapy-related recorded were surgical techniques and cytokine-based therapy. Results: 60% of the patients showed organ-confined disease, 10% of patients with renal cell carcinoma presented with nodal positive disease and 7% with systemic metastases. 42% of patients presenting incidental tumor, with survival rates substantially better than that for symptomatic patients. 42% of patients with nodal positive disease presented systemic metastases at diagnosis, and 30% at surveillance. Systemic metastases portend a particularly poor prognosis for patients with renal cell carcinoma, with 12-months survival rates that 0%. Patients with cytokine-related therapy for metastatic disease presented 24-months survival rates that 20%. Conclusions: Renal cell carcinoma remains a major source of mortality, basically at advanced disease (nodal positive disease or systemic disease), without a clear improvement of survival rates despite the newer therapy modalities.

Caso clínico: Mujer de 21 años con estrías angioides retinianas y estrías cutáneas en axilas y cuello. Tras biopsia cutánea con calcificaciones en las fibras elásticas de dermis, fue diagnosticada de Pseudoxantoma elástico. Remitida al Servicio de Urología por infección del tracto urinario inferior, en estudio ecográfico renal presentó múltiples focos hiperecogénicos de pequeño tamaño en la unión córtico-medular. Comentarios: El Pseudoxantoma elástico es una rara enfermedad genética que se caracteriza por la fragmentación y calcificación de las fibras elásticas de la piel y arterias. Las manifestaciones clínicas incluyen hipertensión, angor pectoris, ictus, claudicación intermitente, hemorragia digestiva alta, estrías angioides retinianas y estrías cutáneas. La ecografía se caracteriza por la presencia de múltiples focos hiperecogénicos a nivel del parénquima renal, pero este hallazgo no es específico del Pseudoxantoma elástico. Sin embargo, la presencia de este patrón ultrasonográfico en pacientes jóvenes con anomalías dermatológicas debe hacernos pensar en este síndrome dentro de las diferentes posibilidades diagnósticas. Aparte de los hallazgos ecográficos descritos, sólo una lesión ureteral en una paciente sometida a ureteroscopia ha sido descrita en relación al ámbito urológico de este síndrome. En nuestro caso, la relación entre esta enfermedad y la presencia de infección urinaria recurrente no esta clara. Case report: A 21-year-old woman presented with retinal angioid streaks and yellowish streak skin abnormalities in neck and axillary folds. Skin biopsy showed bluish-gray tangled masses of calcified elastic fibers in the mid-to lower dermis suggestive of Pseudoxanthoma elasticum (PXE). She consulted in Urology Department for lower urinary tract infection. Renal ultrasonography revealed multiple highly reflective foci in the corticomedullary junction. Comment: Pseudoxanthoma elasticum is a rare genetic disorder characterised by fragmentation and calcification of elastic fibers in the skin and media of arteries. Frequent manifestations include hypertension, angina pectoris, transient cerebral ischemic attacks, intermittent claudication, upper gastrointestinal bledding, retinal angioid streaks and thickened skin. A characteristic appearance of highly reflective foci in the renal parenchyma have been reported in patients with PXE, but it’s not specific for this syndrome. However, the presence of this structural pattern in a young patient with dermatological abnormalities should lead to the consideration of PXE in the differential diagnosis list. Besides ultrasonography findings, only a ureteral disruption case in a patient underwent ureteroscopic manipulation has been described to our knowledge. In our case, the true significance of these disease in recurrent urinary tract infection is uncertain.