The value of andrology medical-surgical training programs for Urology residents. / Importancia de la formación médico-quirúrgica andrológica para los residentes de Urología.

Nowadays, sub-specialty expertise in andrology is required within the Urology training program. These practices -during the MIR (Medical Intern Residency) program and once the specialty studies are over- should be performed under supervision and have a multidisciplinary nature. In fact, the urologist's andrology training program does not finish with his residency period. The unceasingly increasing knowledge related to infertility, reproduction, sexual medicine and reconstructive surgery require a high level of dedication and engagement with continuing education. The field of Andrology has evolved significantly in Europe and in the United States in the past 30 years. Although the andrology training programs in these 2regions share some common aspects, there are also substantial differences between them. This chapter includes a review of the Spanish training programs and those in our international environment, with the objective to comprehend the importance of andrology medical-surgical training for Urology residents.

miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.

Acral Metastasis of the Fingers: Report of 2 Cases. / Metástasis digital acral: presentación de 2casos clínicos.

Cutaneous metastases appear in 0.6% to 10.4% of malignant tumors and account for 2% of all cutaneous tumors. Metastasis to the skin may arise from progression of a known primary tumor or provide the first sign of an unsuspected one. Acral metastases are particularly unusual. Most derive from bone tumors. Clinical signs vary and the lesions generally resemble infection or inflammation, leading to diagnostic delays. When metástasis involves the fingers, the primary tumor is usually lung carcinoma. In contrast, toe involvement usually derives from a tumor in the genitourinary tract. A pathologic diagnosis in these cases is necessary and will suggest the location of the primary tumor. We report 2 cases of metástasis to the fingers. One is the first report of acral metástasis of a myoepithelial carcinoma of the breast. The other concerns acral metástasis as the first sign of lung carcinoma.

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

The Influence of Radon (Gas and Progeny) and Weather Conditions on Ambient Dose Equivalent Rate.

The purpose of this study is to identify the influence of radon (gas and progeny) on the ambient dose equivalent rate measured at the reference station ESMERALDA, where continuous measurements of the ambient dose equivalent rate (every 10 min) combined with activity concentration measurements of radon gas and radon progeny as well as meteorological parameters have been collected. This study has been performed using a correlation study based on a principal components analysis and the Spearman's rank correlation coefficient.

Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments.

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks.

[Vascular morphological and microdensity changes of corneal neovascularization induced by topical bevacizumab and sunitinib in an animal model]. / Cambios en la morfología y la microdensidad neovascular corneal inducidos tras la administración tópica de bevacizumab y sunitinib en un modelo animal.

OBJECTIVE: To evaluate the effects of topical bevacizumab and topical sunitinib on vascular microdensity and morphology of corneal neovascularization (NV). METHODS: A total of 33 rabbits were distributed into 3 groups: group 1 (control; n=11): saline; group 2 (n=11): bevacizumab 5mg/ml; and group 3 (n=11): sunitinib 0.5mg/ml. A corneal NV model was used, based on sutures in the right eye of each rabbit. Each treatment was administered topically 3 times daily for 14 days. Corneas were then processed for the study of vascular microdensity (6 eyes) and vascular morphology analysis (5 eyes) using enzymatic staining histological techniques RESULTS: The vascular response in group 3 was limited to small-sized tree formations with various vascular axes compared with the extensive, lush and directional corneal NV of group 1 and 2. In the histological sections near the limb, there were no differences in vascular microdensity studies between the three groups. However, the mean sectional area of vessels (MSAV) in group 3 was 41.88% lower than in group 1 and 19.19% lower than in group 2. In distal sections, there were no differences between groups 1 and 2. However, group 3 was characterized by absence of vessels. CONCLUSIONS: Bevacizumab produced no changes in the morphology of the vessels or the vascular microdensity. Sunitinib reduced the size of the new vessels and induced changes in the vascular tree.

Prolactin fractions from lactating rats elicit effects upon sensory spinal cord cells of male rats.

Recently it has been suggested that the neurohormone prolactin (PRL) could act on the afferent nociceptive neurons. Indeed, PRL sensitizes transient receptor potential vanilloid 1 (TRPV1) channels present in nociceptive C-fibers and consequently reduces the pain threshold in a model of inflammatory pain. Accordingly, high plasma PRL levels in non-lactating females have been associated with several painful conditions (e.g. migraine). Paradoxically, an increase of PRL secretion during lactation induced a reduction in pain sensitivity. This difference could be attributed to the fact that PRL secreted from the adenopituitary (AP) is transformed into several molecular variants by the suckling stimulation. In order to test this hypothesis, the present study set out to investigate whether PRL from AP of suckled (S) or non-suckled (NS) lactating rats affects the activity of the male Wistar wide dynamic range (WDR) neurons. The WDR neurons are located in the dorsal horn of the spinal cord and receive input from the first-order neurons (Ab-, Ad- and C-fibers). Spinal administration of prolactin variant from NS rats (NS-PRL) or prolactin variant from S rats (S-PRL) had no effect on the neuronal activity of non-nociceptive Ab-fibers. However, the activities of nociceptive Ad-fibers and C-fibers were: (i) increased by NS-PRL and (ii) diminished by S-PRL. Either NS-PRL or S-PRL enhanced the post-discharge activity. Taken together, these results suggest that PRL from S or NS lactating rats could either facilitate or depress the nociceptive responses of spinal dorsal horn cells, depending on the physiological state of the rats.

Interstitial granulomatous dermatitis and arthritis revealing oesophageal carcinoma.

Interstitial granulomatous dermatitis and arthritis (IGDA) is an uncommon clinicopathological condition that may occur in association with a number of systemic disorders. We present a novel case of IGDA in association with oesophageal squamous cell carcinoma (SCC). A 67-year-old man with a 3-month history of arthritis presented with several erythematous indurated plaques on his lateral trunk and arms. An oesophagogastroduodenoscopy showed an irregular mass 20 mm in size in the proximal third of the oesophagus, and on histopathological examination of a biopsy, the mass was identified as a poorly differentiated SCC. Histopathological examination of a skin biopsy found features consistent with interstitial granulomatous dermatitis. The combination of clinicopathological correlation and laboratory findings led to the diagnosis of IGDA. This association has not been previously described, to our knowledge.

[Pyoderma gangrenosum: a report of 15 cases and review of the literature]. / Pioderma gangrenoso: Presentación de 15 casos y revisión de la literatura.

BACKGROUND: Pyoderma gangrenosum is a condition that is included among the neutrophilic dermatoses. Given its low incidence, few studies have addressed its epidemiology or treatment. OBJECTIVE: To describe the epidemiological and clinical characteristics of patients with pyoderma gangrenosum along with our experience of treating the condition in a referral hospital in Malaga, Spain. MATERIAL AND METHODS: A retrospective, observational study was undertaken in the Department of Dermatology at Hospital Clínico Universitario Virgen de la Victoria in Malaga, Spain between January 2000 and December 2009 and included all patients diagnosed with pyoderma gangrenosum. RESULTS: The incidence of pyoderma gangrenosum in our reference population is 3.26 cases per million inhabitants per year. The most frequent concomitant systemic disease was ulcerative colitis (5 cases, 33%). In 4 patients with that disease, pyoderma gangrenosum appeared during a flare-up. In 80% of cases, patients were not referred to a dermatologist during the initial phase of pyoderma gangrenosum, and most referrals were from gastroenterology or general surgery (4 patients each, 52%). CONCLUSIONS: Patients with pyoderma gangrenosum are often referred to dermatologists by other specialists after a varying period of time has elapsed without achieving an accurate diagnosis. In these patients, especially those between 20 and 40 years of age, it is essential to rule out concomitant disease. Adalimumab is a good treatment option for pyoderma gangrenosum.

[The current challenge of imported leprosy in Spain: a study of 7 cases]. / Lepra importada y su dificultad en el medio actual: a propósito de 7 casos.

BACKGROUND: although the foci of leprosy once present in Spain are now under control and almost inactive, isolated cases are still occasionally diagnosed. Meanwhile, population migration has brought about an increase in the incidence of cases corresponding to individuals from countries where leprosy is endemic, leading to changes in the epidemiology of this disease. OBJECTIVES: the aim of this paper was to describe the clinical, epidemiologic, dermatologic, microbiologic, and therapeutic characteristics of cases of leprosy in our department in the last 5 years. MATERIAL AND METHODS: we report the cases of imported leprosy seen in our department between 2004 and 2009. RESULTS: seven patients with leprosy (3 men and 4 women; age range, 26-80 years) were diagnosed; 2 were cases of tuberculoid leprosy, 2 borderline tuberculoid leprosy, and 3 indeterminate. All patients acquired the disease in South American or South African countries, but were residing in Spain at the time of diagnosis. One patient was a Spaniard, from Malaga, who had worked as a missionary in Venezuela for 25 years. The presence of the bacterium by either Ziehl-Neelsen stain or bacilloscopy could not be demonstrated in any of the patients. CONCLUSIONS: we would like to draw attention to the changes we have observed in the characteristics of cases of leprosy seen in our department, the majority of which are imported. It is important to maintain a clinical suspicion of leprosy in cases of granulomatous dermatitis, particularly in patients from countries where the disease is endemic.

[Epidural anesthesia for cesarean section in a patient with von Hippel-Lindau disease]. / Anestesia epidural para cesárea en una paciente con enfermedad de von Hippel-Lindau.

Von Hippel-Lindau disease is a dominant autosomal genetic condition with variable penetrance and expressivity. It is characterized by hemangioblastomas in multiple organs but mainly in the retina and cerebellum. There is a predisposition to carcinoma. We report a cesarean section in a 28-year-old woman with von Hippel-Lindau disease. She had no neurologic symptoms at the time of the operation but a history of ocular and cerebellar involvement and several procedures to remove cerebellar hemangioblastomas. Epidural anesthesia was chosen given that there was no nervous system involvement at the time of surgery.