[Lymphadenectomy for bladder cancer: current status and controversies]

Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template.

[Bone metastasis in prostate cancer]

Bone metastasis and skeletal complications have a devastating impact on the quality of life and are a major cause of morbidity in prostate cancer patients. In addition to established bone-targeted therapies, new drugs such as endothelin A receptor antagonists, MET and VEGFR-2 antagonists or radiopharmaceuticals are in the focus of development. The standard care in prostate cancer patients with bone metastases to prevent skeletal-related events (SRE) are bisphosphonates. Denosumab, a human monoclonal antibody against RANKL, appeared to be superior to zoledronic acid for prevention of SRE and has been shown to prolong bone metastases-free survival. In contrast to zoledronic acid, denosumab clearance is not dependent on kidney function and can be administered subcutaneously. Similar rates of toxicity were observed for both substances; however, long-term data for denosumab are limited.

[Approach to prostate cancer in men older than 75 years: active or passive?]

Based on the exponential aging of the population and the increasing life expectancy in industrialized western countries, prostate cancer (PCa) in elderly men is becoming a disease of increasing significance. Consensus exists that men over the age of 75 years should not be screened for PCa; however, higher age as a single parameter should not exclude men from being diagnosed with prostate cancer and treated accordingly. It is well-known that overdiagnosis and overtreatment are frequent in this age group. Competing mortality risks of men older than 75 years may supersede the risk of dying from PCa several fold. Both the treating physician and the patient himself should therefore balance the possible risks and benefits of diagnosing and treating prostate cancer concerning the impact on quality of life. This is of special importance when taking into account that the complication rates of curative treatment modalities are higher in older patients than in younger men and that hormonal treatment might have negative effects especially in older men.Age, existing comorbidities, cognitive and physical status in combination with specific tumor parameters are useful tools for an individualized treatment.Therapy should be considered for healthy, active men aged 75 years or older who present with high-risk PCa and/or with a PSA doubling time <12 months. Elderly men who are unfit or have low to intermediate risk PCa will most likely not benefit from treatment.

[Secondary malignancies in urinary diversions]

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

[How should hormone therapy for castration-resistant prostate cancer be continued?]

After an average of 18-36 months under androgen suppression therapy by surgical castration, LHRH, and steroidal or non-steroidal antiandrogens, almost all patients with metastatic prostate cancer show PSA progression as a sign of androgen-independent but still androgen-sensitive tumor growth. Our understanding and the treatment of such castration-resistant prostate cancer has changed markedly. The introduction of new drugs like abiraterone and MDV3100 has shown that prostate cancer progression even in the"hormone-refractory" stage is driven by androgen receptor signaling. Based on this information the question of whether androgen deprivation therapy in castration-resistant prostate cancer should be continued or not is still of relevance. This review gives a critical overview of the literature and current guideline recommendations.

Neuronal differentiation of human mesenchymal stem cells: changes in the expression of the Alzheimer's disease-related gene seladin-1

Seladin-1 (SELective Alzheimer's Disease INdicator-1) is an anti-apoptotic gene, which is down-regulated in brain regions affected by Alzheimer's disease (AD). In addition, seladin-1 catalyzes the conversion of desmosterol into cholesterol. Disruption of cholesterol homeostasis in neurons may increase cell susceptibility to toxic agents. Because the hippocampus and the subventricular zone, which are affected in AD, are the unique regions containing stem cells with neurogenic potential in the adult brain, it might be hypothesized that this multipotent cell compartment is the predominant source of seladin-1 in normal brain. In the present study, we isolated and characterized human mesenchymal stem cells (hMSC) as a model of cells with the ability to differentiate into neurons. hMSC were then differentiated toward a neuronal phenotype (hMSC-n). These cells were thoroughly characterized and proved to be neurons, as assessed by molecular and electrophysiological evaluation. Seladin-1 expression was determined and found to be significantly reduced in hMSC-n compared to undifferentiated cells. Accordingly, the total content of cholesterol was decreased after differentiation. These original results demonstrate for the first time that seladin-1 is abundantly expressed by stem cells and appear to suggest that reduced expression in AD might be due to an altered pool of multipotent cells.

High-Pressure Behavior and Phase Stability of Al5BO9, a Mullite-Type Ceramic Material

Phase stability, elastic behavior, and pressure-induced structural evolution of synthetic boron-mullite Al5BO9 (a = 5.6780(7), b = 15.035(6), and c =7.698(3) Å, space group Cmc21, Z = 4) were investigated up to 25.6(1) GPa by in situ single-crystal synchrotron X-ray diffraction with a diamond anvil cell (DAC) under hydrostatic conditions. No evidence of phase transition was observed up to 21.7(1) GPa. At 25.6(1) GPa, the refined unit-cell parameters deviated significantly from the compressional trend, and the diffraction peaks appeared broader than at lower pressure. At 26.7(1) GPa, the diffraction pattern was not indexable, suggesting amorphization of the material or a phase transition to a high-pressure polymorph. Fitting the P–V data up to 21.7(1) GPa with a second-order Birch–Murnaghan Equation-of-State, we obtained a bulk modulus KT0 = 164(1) GPa. The axial compressibilities, here described as linearized bulk moduli, are as follows: KT0(a) = 244(9), KT0(b) = 120(4), and KT0(c) = 166(11) GPa (KT0(a):KT0(b):KT0(c) = 2.03:1:1.38). The structure refinements allowed a description of the main deformation mechanisms in response to the applied pressure. The stiffer crystallographic direction appears to be controlled by the infinite chains of edge-sharing octahedra running along [100], making the structure less compressible along the a-axis than along the b- and c-axis.

Historia y mito en Yo, el supremo de Augusto Roa Bastos

Yo el supremo (1974), la segunda novela de Augusto Roa Bastos. Se presenta como un tejido de elementos provenientes de diversos escritos de diferente origen: míticos, bíblicos, históricos y literarios. La riqueza de este texto múltiple ha posibilitado un importante cúmulo de estudios que subrayan, su contenido histórico, ideológico, político, intertextual y carnavalesco. Sin embargo, algunas de esas interpretaciones son literales y no penetran en el universo latente y profundo que el texto sugiere. La novela ofrece varios niveles de lectura porque además de lo lingüístico y lo histórico está lo legendario y folklórico, lo actual, lo mítico y lo simbólico. Este trabajo se plantea como una lectura desde los presupuestos de la psicología profunda, limitándose, dentro de este inmenso y prolífico campo, al análisis de los elementos arquetípicos vinculados con el tema del la búsqueda de la identidad y los mitos del héroe y del renacimiento. Las características oníricas, las distorsiones y condensaciones que comparte con el mundo de los sueños y de los mitos, la eliminación del tiempo y del espacio son elementos presentes en la novela que justifican el abordaje elegido. Así se analizan en el texto las imágenes y símbolos vinculados a los ritos de iniciación, la aventura del héroe, los estadios del proceso de individuación de Jung y el patrón del héroe de Campbell y el mito de Osiris.

Riqueza de un entremés: Las Carnestolendas, de Pedro Calderón de la Barca

Junto a las magistrales creaciones barrocas del genial dramaturgo don Pedro Calderón de la Barca, encontramos una rica producción de piezas cortas, cuya primera publicación data de 1645, en Entremeses Nuevos, momento en que el género entremés ofrecía ya un corpus considerable de obras, motivos, tipos y argumentos a los cuales, se dice, Calderón hace avanzar en algunos casos con genialidad hasta su plena madurez. El arte de Calderón, como cima de la creación dramática barroca, se hace presente también en las piezas de su teatro breve, tanto en los aspectos del estilo como en los de la concepción y elaboración de la pieza dramática. Las Carnestolendas es un excelente ejemplo de ese arte. El análisis de este entremés intenta demostrar que la riqueza y la complejidad que posee es una síntesis apretada del arte barroco calderoniano. Ello se ejemplifica con los distintos aspectos propios del entremés aunque presentes también en las comedias: la unidad dramática, la cohesión de los distintos momentos, la tensión, los temas, el teatro dentro del teatro, el desfile de personajes, la comicidad verbal. Puede apreciarse, así, que Las carnestolendas son como el "mundo abreviado" de la comedia calderoniana.

Victoria Ocampo en El archipiélago : recuerdos de infancia y sociedad

Este trabajo se dedica en especial al estudio del primer volumen de la Autobiografía de Victoria Ocampo, denominada El Archipiélago. Si bien partimos de la convicción de que la escritura refleja la época y el medio en el que surge, este análisis no pretende validar de modo exclusivo este enfoque, sino insertarse antropológicamente en las actitudes vitales que conducen, partiendo del discurso creativo-confesional, al testimonio sobre la realidad argentina. Entre las escritoras de comienzo de siglo -Delfina Bunge, María Rosa Oliver, Norah Lange- Victoria Ocampo se destaca por una búsqueda lúcida y autónoma en donde la reflexión prepondera y encuentra en el discurso autorreferido el modo más acertado de ser testigo-protagonista y crítico a la vez. Sus alegatos -condicionados por circunstancias personales- aciertan a constituir en su conjunto, un archipiélago fundante de intenso y fecundo diálogo con políticos, escritores, músicos de diferente origen. En este marco apreciativo se destacará la importancia de sus "recuerdos de infancia" y de sus "testimonios" sobre nuestra sociedad, en el medio siglo que nos antecede. Este primer volumen, de los seis que componen su Autobiografía, se suma al ya creciente corpus de la literatura autorreferida en la Argentina y favorece los estudios específicos sobre los "recuerdos de infancia" como un género discursivo que participa tanto de la autobiografía propiamente dicha como de la novela lírica.

Poética del cuento de Julio Cortázar

Cortázar es un autor que ha sido estudiado parcialmente. Los textos críticos que ha suscitado su producción literaria dejan aspectos importantes sin considerar. La originalidad de su obra ficcional ha sido destacada de manera más unánime que la lucidez teórica de sus escritos no ficcionales. La dificultad tal vez se encuentre en el hecho de que no hay un volumen especifico de Cortázar que recoja su singular teoría del cuento sino que sus reflexiones se hallan diseminadas en sus ensayos, ficciones y en las entrevistas que el autor concede a la prensa. Creo pues necesario sistematizar, de manera sintética, su concepción del cuento para considerar su aporte tanto en la investigación del género cuento como en su original teoría de lo fantástico.

Santiago de Estrada : su viaje al Perú

Este trabajo se centra en el estudio de la sección "De Valparaíso a La Oroya", que abarca más de doscientas páginas de las trescientas sesenta y dos del segundo tomo de los Viajes de Santiago Estrada (1889). Se analiza el texto desde la literatura comparada como un texto de viajes en el cual resultan evidentes las constantes antropológicas y estéticas de este tipo de discurso, según lo establecen los estudios teóricos al respecto. Desde el punto de vista antropológico se observa cómo el autor retrata los distintos aspectos de una experiencia viajera corta pero significativa. Desde lo estético se pueden apreciar las estrategias discursivas que ordenan el material de acuerdo con las intenciones panamericanistas del autor y que evidencian su filiación romántica.