Showing papers by "Javier C. Angulo published in 2013"

Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double‐blind, placebo‐controlled, phase III studies

Abstract: Introduction To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.

Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial

Abstract: Background Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a β3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points – mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naive patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability.

Preserved endothelial function in human obesity in the absence of insulin resistance

Abstract: Background Insulin resistance (IR) is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD). On the other hand, obesity has long been related to IR and increased CVD. However it is not known if IR is a necessary condition for endothelial dysfunction in human obesity, allowing for preserved endothelial function in obese people when absent. Therefore, the purpose of the study was to assess the relationship between IR and endothelial dysfunction in human obesity and the mechanisms involved.

Estado actual de la cirugía transumbilical por puerto único en urología: retos y aplicaciones

Abstract: Resumen Contexto La cirugia laparoscopica en urologia ha supuesto un avance importante, aunque no esta exenta de cierta morbilidad asociada al empleo de multiples trocares y de forma particular a la extraccion del especimen. Con intencion de disminuir esta morbilidad y de mejorar la estetica se estan desarrollado otras tecnicas, como la cirugia laparoendoscopica a traves de orificios naturales (NOTES) y la cirugia laparoendoscopica a traves de puerto unico (LESS). Se pretende revisar el estado actual de la cirugia laparoendoscopica por puerto unico en urologia. Adquisicion de evidencia Se ha llevado a cabo una revision no sistematica, a traves de una busqueda bibliografica empleando los terminos LESS y urologia desde 2007 hasta 2012. Se describen la experiencia actual LESS en urologia, sus principales indicaciones y los diferentes dispositivos de puerto unico e instrumental disponibles en el mercado. Sintesis de evidencia La cirugia LESS nace como un paso mas en la evolucion constante de la cirugia minimamente invasiva en un intento por mejorar la estetica, reducir el traumatismo quirurgico y disminuir el dolor y las complicaciones postoperatorias asociadas a la laparoscopia convencional con multiples trocares. Desde la primera descripcion en 2007, la experiencia se ha incrementado exponencialmente y la tecnica LESS, asistida o no por robot, se esta consolidando para un gran espectro de indicaciones urologicas (tanto en cirugia oncologica como reconstructiva), a mucha mayor escala que la tecnica NOTES. A pesar de que la mayoria de los datos existentes son no aleatorizados y en escasas ocasiones son comparativos, con el sesgo de seleccion que ello representa, parece evidente que el beneficio estetico y de control analgesico asociado a la cirugia LESS es real y reproducible. Las complicaciones asociadas a la misma son mayores en casos de cirugia oncologica mayor y se deben mas a la propia tecnica que al abordaje. Conclusiones Aunque el beneficio real de la cirugia LESS en urologia aun no puede cuantificarse oportunamente, la mejora cosmetica, el menor dolor y una mayor satisfaccion del paciente con su herida resultan evidentes. El entrenamiento apropiado en este tipo de procedimientos en centros de gran volumen y las constantes mejoras tecnicas en el desarrollo instrumental por parte de la industria biomedica permiten que la tecnica LESS transumbilical en urologia haya nacido para quedarse.

The study of DNA methylation in urological cancer: present and future

Abstract: Objectives We have synthesized the principal advances in the field of the study of epigenetics and specifically DNA methylation regarding the diagnosis of urological neoplasms. Acquisition of evidence Review of the literature (PubMed, MEDLINE y COCHRANE) on the study of DNA methylation in urological neoplasms (prostate cancer, bladder cancer, renal cancer and testicular cancer), considering all the studies published up to January 2013. Synthesis of evidence It was possible to determine the state of methylation of many genes in our tumor samples. When these were compared with healthy tissue samples, it was possible to define the specific aberrant methylation patterns for each type of tumor. The study and definition of specific abnormal methylation patterns of each type of tumor are a tool having potential utility for diagnosis, evaluation, prediction of prognosis and treatment of the different forms of genitourinary cancer. The analysis of gene methylation in urine after micturition or post-prostatic massage urine, semen, in the wash plasma or fluid from prostatic biopsies may allow early detection of bladder, prostate, renal and testicular cancer. In each one of the neoplasms, an epigenetic signature that may be detected in the DNA has been identified, obtained from very scarce or not at all invasive specimens, with potential in the diagnosis and evaluation of prognosis. Validation of these studies will confirm the accuracy, effectiveness and reproducibility of the results available up to now. Criteria have still not been developed that determine if a gene panel provides sufficient information in the health care practice to guide an unequivocal diagnosis or therapeutic conduct. More studies are needed to compare sensitivity, specificity, positive and negative predictive value of the test in each case. Multicenter studies analyzing the real reproducibility of these results in a clinical setting also do not exist. Conclusions The study of aberrant DNA methylation in biological specimens of patients has an enormous potential for the early diagnosis and screening of genitourinary neoplasms. A larger number of studies is needed to be able to define the series of genes that would mean unequivocal signatures of malignancy. This methodology also has potential when defining prognostic groups and potential of response to different therapies.

Current state of single-port transumbilical surgery in urology: Challenges and applications ☆

Abstract: Context Laparoscopic surgery in urology is considered to be an important advance, although it is not exempt from some morbidity associated to the use of multiple trocars and specifically to the extraction of the specimen. In order to decrease this morbidity and improve esthetics, other techniques are being developed, such as natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS). It is aimed to review the current status of laparoendoscopic single site surgery in urology. Acquisition of evidence A nonsystematic review has been carried out by means of the bibliographic search using the terms LESS and Urology from 2007 to 2012. The current LESS experience in urology is described, and its principal indications and the different single site devices and instruments available on the market are described. Synthesis of evidence LESS surgery arose as one more step in the constant evolution of minimally invasive surgery in an attempt to improve esthetics, reduce surgical trauma and decrease pain and the post-operative complications associated to the conventional laparoscopy with multiple trocars. Since it was first described in 2007, the experience has been increasing exponentially and the LESS technique, whether assisted or not by robot, is becoming consolidated for a large spectrum of urological indications (both in oncological and reconstructive surgery) on a much greater scale than the NOTES technique. Even though most of the existing data are not randomized and very rarely comparative, with the selection bias that this represents, it seems clear that the esthetic benefit and analgesic control associated to the LESS surgery is real and reproducible. The complications associated to it are greater in cases of major oncology surgery and are due more to the technique itself then to the approach. Conclusions Although the real benefit of the LESS surgery in urology cannot be appropriately quantified, the cosmetic improvement, less pain and greater patient satisfaction with their wound are clear. Appropriate training in this type of procedures in centers having large volumes and the continuous technical improvements in the instrumental development by the biomedical industry has resulted in the fact that the transumbilical LESS technique in urology has been born to stay.

Randomized comparative study for the assessment of a new therapeutic schedule of fosfomycin trometamol in postmenopausal women with uncomplicated lower urinary tract infection

Abstract: Objectives To compare two therapeutic regimes in terms of bacterial eradication of post-menopausal with uncomplicated acute cystitis who complete antibiotic treatment. Materials and methods A multicenter, randomized, prospective and controlled study between two short antibiotic regimes: fosfomycin trometamol (FMT) 3 g, 2 doses separated by 72 h and ciprofloxacin 250 mg every 12 h for 3 days. A total of 118 post-menopausal women were enrolled in the study. They underwent an initial urine culture to know the responsible microorganism and susceptibility to treatment. This was repeated 5–7 days and 4 weeks after the treatment to evaluate bacterial eradication. Clinical symptoms and treatment safety were also evaluated. Results There were microbiological data at the onset of the treatment in 82 women (69.49%). Of these, 27 did not have positive culture at the first visit (30.51%), 76 (64.41%) fulfilled all the protocol requirements and adverse effects from the treatment were collected in 113 (95.76%) of the patients enrolled in the study. The germs isolated most frequently were Escherichia coli (E. coli) (76.83%), Klebsiella pneumoniae (K. pneumoniae) (7.32%), Proteus mirabilis (P. mirabilis) (4.89%) and Enterococo sp. (3.66%). In terms of efficacy, no differences were detected in the proportion of patients who achieved bacterial eradication between the two study arms: 62.16% of the patients who received FMT and 58.97% of those treated with ciprofloxacin (Chi-square, p = 0.78). The proportion of patients who achieved clinical cure was also similar (86.49% for FMT and 82.05% for ciprofloxacin; square, p = 0.59). These results indicate similar efficacy of both antibiotics in the treatment of uncomplicated lower tract urinary infection in post-menopausal women. In regards to safety data, the proportion of global adverse effects associated to the treatments was 3.45% for FMT and 9.09% for ciprofloxacin. Treatment compliance was 100% for FMT and 83.64% for ciprofloxacin. Conclusions The FMT administered at a dose of 3 g every 72 h (2 total doses) and ciprofloxacin at a dose of 250 mg every 12 h during 3 days (6 total doses) have a comparable efficacy profile in lower tract urinary infection in post-menopausal women who adequately comply with the treatment, also having comparable safety. The FMT has a better antimicrobial susceptibility profile and better rate of treatment compliance.

Análisis de los factores que influyen en la pérdida hemática en la nefrolitotomía percutánea: registro de la Asociación Española de Urología sobre la posición supina

Abstract: Resumen Objetivo La nefrolitotomia percutanea (NLP) es la tecnica minimamente invasiva de eleccion para el tratamiento de la litiasis renal mayor de 2 cm. El objetivo de este estudio es analizar los diferentes factores que influyen en el descenso de hemoglobina durante el procedimiento, realizado en posicion supina. Material y metodos Realizamos un estudio prospectivo multicentrico observacional de la nefrolitotomia percutanea en posicion supina, basado en el registro de la AEU. Se estudian los diferentes factores que influyen en el descenso de hemoglobina: datos demograficos y antropometricos, comorbilidad asociada, localizacion y tamano de la litiasis, variantes anatomicas y aspectos tecnicos del procedimiento. Resultados Desde septiembre de 2008 hasta diciembre de 2012 se han registrado 397 NLP en posicion supina, realizadas en 15 centros espanoles. El descenso medio de hemoglobina fue 2,3 ± 1,5 g/dl y la tasa de transfusion de 5,5%. No hubo diferencias significativas en el descenso de hemoglobina entre varones y mujeres, IMC ni por grupos de edad. Tampoco existen diferencias entre los pacientes con antecedentes cardiovasculares, diabetes, HTA o tratamiento anticoagulante. El tamano y la localizacion de la litiasis no influyen de forma significativa en la perdida hematica. La duracion del procedimiento (> o (tubeless) no afectaron al descenso de hemoglobina. Unicamente el numero de trayectos percutaneos (≥ 2) y el acceso a traves de un caliz medio tuvieron repercusion estadisticamente significativa en la perdida hematica (p = 0,03 y p = 0,01 respectivamente). Conclusiones La NLP en posicion supina es un procedimiento minimamente invasivo para el tratamiento de litiasis renales multiples y de gran tamano (> 2 cm), que implica escasa perdida hematica, con minima tasa de transfusion de hemoderivados. Los unicos factores relacionados con mayor descenso de hemoglobina fueron el numero de accesos percutaneos y la localizacion del trayecto en el caliz medio.

Evidence available on the use of the selective β3-adrenoceptor agonist mirabegron for the treatment of overactive bladder.

Abstract: Context Mirabegron, the selective β3-adrenoceptor agonist, heralds the latest development for the treatment of overactive bladder (OAB). Objective To present the evidence available on the efficacy and tolerability of mirabegron and to discuss this treatment's potential in our setting. Evidence acquisition We reviewed 11 studies conducted with mirabegron in patients with OAB (2 phase ii , 9 phase iii ), all studies were compared to placebo with 6 studies also including tolterodine as an additional arm. Greater emphasis shall be given to the main phase iii trials performed in Europe, the USA and Australia evaluating efficacy and safety after 12 weeks ( NCT00662909 , NCT00689104 , NCT00912964 ) and safety after 12 months ( NCT00688688 ). The combined analyses of these 12-week studies are also available, with emphasis on global efficacy (FAS), efficacy with regard to incontinence (FAS i ) and safety (SAF). More than 50% of patients had previously discontinued anticholinergics medication for OAB, thus allowing us to obtain data on the effectiveness of mirabegron in patients already treated with anticholinergics. Evidence synthesis Mirabegron is an efficacious drug which presents a statistically significant reduction in the number of incontinence episodes and in urinary frequency as of 4 weeks, with a higher percentage of dry patients and a higher percentage of patients with reduction ≥50% in the number of incontinence episodes than placebo. The efficacy of mirabegron 50 and 100 mg in the reduction of incontinence episodes occurs in de novo patients and who have received antimuscarinics, with adjusted mean difference and improvement in urinary frequency greater in treated patients. Its tolerability is very similar to placebo particularly for the adverse effects of the antimuscarinics (dry mouth, constipation and blurred vision). A minimal, non-clinically significant change is observed in systolic and diastolic blood pressure and pulse. Its efficacy is long-term. Mirabegron at the doses of 50 and 100 mg presents an improvement versus placebo in patient satisfaction, health-related quality of life (HRQoL), symptom bother and patient's perception of bladder condition (PPBC). In the 12-week phase III European study tolterodine deliverred a lesser degree of improvement than mirabegron versus placebo in patient satisfaction, HRQoL, symptom bother and PPBC. Conclusions Mirabegron is the first of a new class of compounds with a novel mechanism of action that is different to the antimuscarinics. It presents significant and clinically important efficacy in the treatment of the symptoms of OAB. It has advantages with regard to the results described by the patient in treatment satisfaction. Studies on its combined use with anticholinergics are ongoing.

Estudio comparativo aleatorizado para la evaluación de un nuevo esquema terapéutico de fosfomicina trometamol en mujeres posmenopáusicas con infección no complicada del tracto urinario inferior

Abstract: Objectives To compare two therapeutic regimes in terms of bacterial eradication of post-menopausal with uncomplicated acute cystitis who complete antibiotic treatment.

El papel de la metaloproteinasa de la matriz MMP-9 y del inhibidor tisular de metaloproteinasa TIMP-2 como marcadores séricos de cáncer vesical

Abstract: Resumen Introduccion El diagnostico y la estadificacion molecular del cancer vesical basados en la deteccion de ARNm de gelatinasas (MMP-2 y MMP-9) en celulas circulantes y mononucleares de sangre periferica han mostrado resultados prometedores. Analizamos si la determinacion de los correspondientes productos de sintesis proteica permite diagnosticar y caracterizar pacientes con neoplasia vesical. Material y metodo Se ha llevado a cabo la cuantificacion de los niveles sericos de MMP-2, MMP-9 y TIMP-2 en una serie de 42 individuos (31 pacientes con cancer vesical en diversos estadios y 11 controles sanos) mediante tecnica de ELISA. Se compararon las determinaciones entre casos y controles (U Mann-Whitney), asi como entre diferentes grupos de tumores (U Mann-Whitney o Kruskal-Wallis), segun las caracteristicas clinico-patologicas (edad, sexo, categoria T, categoria M o grado). Se evaluo el rendimiento diagnostico de estos marcadores mediante analisis de curvas ROC. Resultados Existe correlacion entre las determinaciones de MMP-2 y TIMP-2 (R = 0,699; p > 0,0001) y de MMP-9 y TIMP-2 (R = 0,305; p = 0,049). Los pacientes con cancer de vejiga presentan niveles mas elevados de MMP-9 (p Conclusiones Los resultados obtenidos sugieren que tanto MMP-9 como TIMP-2 sericos podrian tener una aplicacion en la prediccion del desarrollo y progresion del cancer vesical, y potencial utilidad como marcadores clinicos de la enfermedad. Se requieren estudios multicentricos prospectivos que confirmen estos resultados preliminares.

Evidencia disponible acerca del uso del agonista β3-adrenoceptor selectivo mirabegrón para el tratamiento de la vejiga hiperactiva

Abstract: Resumen Contexto Mirabegron, agonista adrenoreceptor β3, supone el ultimo desarrollo farmacologico para el tratamiento de la vejiga hiperactiva (VH). Objetivo Presentar la evidencia disponible respecto a la eficacia y tolerancia de mirabegron y discutir el potencial de dicho tratamiento en nuestro entorno. Adquisicion de evidencia Se revisan 11 estudios llevados a cabo con mirabegron en pacientes con VH (2 fase ii , 9 fase iii ), todos en comparacion con placebo y 6 de ellos incluyeron tambien tolterodina como brazo adicional. Se hace mayor enfasis en los principales ensayos fase iii llevados a cabo en Europa, EE. UU. y Australia que evaluan la eficacia y seguridad a 12 semanas (NCT00662909, NCT00689104, NCT00912964) y la seguridad a 12 meses (NCT00688688). Se dispone tambien del analisis combinado de dichos estudios a 12 semanas, enfatizando en la eficacia global (FAS), la eficacia relativa a la incontinencia (FAS- i ) y la seguridad (SAF). Mas del 50% de los pacientes habia abandonado previamente la medicacion anticolinergica para VH, lo que permite tambien obtener datos acerca de la efectividad de mirabegron en pacientes tratados previamente con anticolinergicos. Sintesis de evidencia Mirabegron es un farmaco eficaz que muestra una reduccion estadisticamente significativa en numero de episodios de incontinencia y en frecuencia miccional a partir de la 4. a semana, con mayor porcentaje tanto de pacientes secos como de pacientes con reduccion ≥ 50% en numero de episodios de incontinencia que placebo. La eficacia de mirabegron 50 y 100 mg en la reduccion en episodios de incontinencia sucede en pacientes nuevos y que han recibido antimuscarinicos, siendo la diferencia media ajustada y la mejora en la frecuencia miccional mayor en pacientes tratados. Su tolerancia es muy similar a placebo, particularmente para los efectos adversos de los antimuscarinicos (boca seca, estrenimiento y vision borrosa). Se aprecia un cambio minimo no clinicamente significativo en la presion arterial sistolica, en la diastolica y en el pulso. Su eficacia se mantiene a largo plazo. Mirabegron a dosis de 50 y 100 mg presenta mejoria frente placebo en la satisfaccion del paciente, en la calidad de vida relacionada con la salud (HRQoL), en las molestias de sintomas y en la percepcion del paciente de la condicion vesical (PPBC). En el estudio europeo fase iii a 12 semanas tolterodina proporciono mejoria en menor medida que mirabegron frente a placebo en la satisfaccion del paciente, HRQoL, molestia de sintomas y PPBC. Conclusiones Mirabegron es el primero de una nueva clase de compuestos con un mecanismo de accion peculiar y diferente a antimuscarinicos. Presenta eficacia significativa y clinicamente importante para tratar los principales sintomas de la VH. Muestra ventajas respecto a los resultados descritos por el paciente sobre la satisfaccion con el tratamiento. Se encuentran en desarrollo estudios relativos a su empleo combinado con anticolinergicos.

El estudio de la metilación del ADN en el cáncer urológico: presente y futuro

Abstract: Resumen Objetivos Realizar una sintesis de los principales avances en el campo del estudio de la epigenetica y concretamente la metilacion de ADN respecto al diagnostico de las neoplasias urologicas. Adquisicion de evidencia Revision de la literatura (PubMed, Medline y Cochrane) sobre el estudio de la metilacion del ADN en neoplasias urologicas (cancer de prostata, cancer de vejiga, cancer renal y cancer testicular) teniendo en cuenta todos los estudios publicados hasta enero de 2013. Sintesis de evidencia Resulta posible determinar el estado de metilacion de un gran numero de genes en muestras de tumores, que al compararlo con muestras de tejido sano permite la definicion de patrones de metilacion aberrantes especificos para cada tipo de tumor. El estudio y la definicion de patrones de metilacion anomala especificos de cada tipo de tumor es una herramienta de potencial utilidad para el diagnostico, evaluacion, prediccion de pronostico y tratamiento de las diferentes formas de cancer genitourinario. El analisis de la metilacion de genes en la orina, tras la miccion o masaje prostatico, el semen, el plasma o el liquido de lavado de biopsias prostaticas puede permitir la deteccion precoz del cancer vesical, prostatico, renal y testicular. En cada una de las neoplasias se ha identificado una firma epigenetica que puede detectarse en ADN obtenido de muestras muy escasamente o nada invasivas, con potencial en el diagnostico y en la evaluacion de pronostico. La validacion de estos estudios confirmara la precision, efectividad y reproducibilidad de los resultados de los que se dispone hasta el momento. No estan aun desarrollados criterios que determinen que un panel de genes sea lo suficientemente informativo en la practica asistencial como para guiar un diagnostico inequivoco o una conducta terapeutica. Se requiere un mayor numero de estudios para contrastar en cada caso la sensibilidad, especificidad, el valor predictivo positivo y negativo de la prueba. Tampoco existen estudios multicentricos que analicen la reproducibilidad real de estos resultados en un entorno clinico. Conclusiones El estudio de la metilacion aberrante del ADN en muestras biologicas de pacientes tiene enorme potencial para el diagnostico precoz y cribado de las neoplasias genitourinarias. Se necesita un mayor numero de estudios que permitan definir baterias de genes que supongan firmas inequivocas de malignidad. Esta metodologia tiene tambien potencial a la hora de definir grupos pronostico y potencial de respuesta a diferentes terapias.

Initial Experience of Umbilical Laparoendoscopic Single-Site Nephron-Sparing Surgery with KeyPort and DuoRotate System

Abstract: Objectives: To present the feasibility of laparoendoscopic single-site (LESS) nephron-sparing surgery (NSS) using new reusable umbilical single-port system and instruments. Methods: A prospective study was performed to evaluate operative data and patient outcomes after LESS-NSS with KeyPort®, a tri-channel single-port placed through a 2.5-cm umbilical incision, and specific DuoRotate® instruments. Patient characteristics, operative time, estimated blood loss (EBL), complications, visual analog pain scale (VAPS), and visual analogue wound satisfaction scale (VAWSS) scores were registered. Results: Six consecutive nonselected patients with indication of NSS and normal contralateral kidney were offered LESS-NSS. An accessory 3.5 mm port that facilitated renoraphy and unclamped technique was used in 4 (66.7%) cases each. Median tumor maximum size was 4.0 (1–7.5) cm; age 64 (31–76) years; body mass index 28.4 (22.1–39.3) kg/m2; operative time 233.5 (140–250) min; EBL 500 (200–500) mL; difference in he...

Analysis of the factors affecting blood loss in percutaneous nephrolithotomy: A registry of the Spanish Association of Urology in the supine position

Abstract: Objective Percutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2 cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position. Materials and methods A prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure. Results From September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3 ± 1.5 g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (>120 min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥2) and middle calix access were statistically significantly ( P = .03 and P = .01) related with less blood loss. Conclusions PCNL in supine position is a minimally invasive procedure for removal of large (≥2 cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels.

Original articleThe role of matrix metalloproteinase MMP-9 and TIMP-2 tissue inhibitor of metalloproteinasas as serum markers of bladder cancerEl papel de la metaloproteinasa de la matriz MMP-9 y del inhibidor tisular de metaloproteinasa TIMP-2 como marcadores séricos de cáncer vesical☆

Abstract: Introduction The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer.

Ureterectomy in the treatment of urothelial carcinoma of the distal ureter

Abstract: Resumen Introduccion La ureterectomia segmentaria con preservacion del rinon es una opcion de tratamiento para el carcinoma urotelial de bajo grado (CUBG) en el ureter distal no susceptible de reseccion endoscopica. La ureterectomia distal laparoscopica (UDL) con reimplantacion ureteral es habitual en un proceso patologico benigno (estenosis, lesion iatrogenica, endometriosis), pero se ha descrito escasamente en enfermedad ureteral maligna. Se revisa la literatura al respecto y se describe la tecnica quirurgica. Material y metodos Se expone la experiencia relativa a 2 casos de UDL por carcinoma urotelial de bajo grado en el ureter distal. En ambos se llevo a cabo RTU vesical previa, la citologia urinaria fue negativa y los estudios de imagen identificaron obstruccion urinaria y defecto de llenado en el ureter distal. Uno de los pacientes tenia antecedentes de neoplasia vesical T1G3 y padecia insuficiencia renal. En ambos el ureter se ligo precozmente. La ureterectomia segmentaria se practico mediante procedimiento combinado endoscopico y laparoscopico con desinsercion ureteral en un caso, y en el otro de forma exclusivamente laparoscopica; ambos con 4 trocares. La reimplantacion ureteral se llevo a cabo con sutura continua hermetica y sin tension. En un caso con antecedente de tumor vesical de alto grado se practico tambien linfadenectomia pelvica. Resultados El tiempo operatorio fue 180 y 240 min, respectivamente; el sangrado estimado 100 y 250 ml y el tiempo de ingreso 6 y 4 dias. La unica complicacion postoperatoria fue ileo paralitico (Clavien I) en el primer caso. Con un seguimiento de 20 y 12 meses no hay evidencia de recidiva ni de dilatacion. En el paciente con insuficiencia renal el aclaramiento de creatinina mejoro. Conclusiones La UDL con reimplantacion ureteral es una tecnica compleja, pero representa una alternativa factible y efectiva para el tratamiento del CUBG en el ureter distal, siempre que se respeten los principios oncologicos y reconstructivos.

Evaluación del riesgo de invasión muscular, afectación perivesical y/o ganglionar mediante resonancia magnética nuclear balanceada con difusión en el paciente candidato a cistectomía radical

Abstract: Introduccion La estadificacion preoperatoria del cancer vesical por metodos de imagen presenta serias limitaciones. Se evalua la exactitud de la resonancia magnetica abdominal balanceada con difusion (MRI-DW) para predecir invasion muscular residual, afectacion perivesical y/o ganglionar en el especimen de cistectomia. Material y metodos Estudio prospectivo sobre 20 pacientes con cancer de vejiga musculo-invasivo de alto grado que recibieron RTU vesical en un plazo menor de un mes. Se realizo MRI-DW antes de cistectomia radical y el radiologo predijo invasion muscular, afectacion extravesical y afectacion ganglionar de manera ciega al estudio histopatologico. Se analizo sensibilidad (S), especificidad (E), valor predictivo positivo (VPP), valor predictivo negativo (VPN) y exactitud (Ex) de la prueba. Se compararon medianas de valor ADC (Mann-Whitney) y se llevo a cabo estudio de curvas ROC para MRI-DW y ADC. Resultados La distribucion por categorias fue: pT0 1(5%), pT1 6(30%), pT2 2(10%), pT3 8(40%) y pT4 3(15%). Existio acuerdo en la asignacion T-pT en 17 (85%). En 7 (35%) hubo afectacion ganglionar (pN1-2). La consistencia de MRI-DW para afectacion muscular fue k = 0,89 (IC 0,67-1; S = 1,0, E = 0,86, VPP = 0,93, VPN = 1,0, Ex = 0,95), para afectacion de grasa perivesical k = 0,6 (IC 0,25-0,95; S = 0,8, E = 0,8, VPP = 0,8, VPN = 0,8, Ex = 0,8) y para afectacion ganglionar k = 0,89 (IC 0,67-1; S = 0,86, E = 1,0, VPP = 1,0, VPN = 0,93, Ex = 0,95). La media de valor de ADC fue mayor en tumores G2 (OMS 1987) frente a G3 (p = 0,08). La evaluacion por imagen de MRI-DW y el valor numerico ADC mostraron areas bajo la curva equivalentes para afectacion muscular (0,93 y 0,9; Z = 0,7), grasa (0,8 y 0,91; Z = 0,31) y ganglionar (0,93 y 0,97; Z = 0,36), respectivamente. Conclusiones MRI-DW permite una buena evaluacion preoperatoria del paciente candidato a cistectomia, especialmente para la prediccion de afectacion muscular (< pT2 vs ? pT2) y/o ganglionar (N0 vs N1-2), ambos puntos clave para elegir la actitud terapeutica despues de RTU vesical. Ademas, el coeficiente ADC predice tambien el grado de diferenciacion tumoral.

Evaluation of risk of muscle invasion, perivesical and/or lymph node affectation by diffusion-weighted magnetic nuclear resonance in the patient who is a candidate for radical cystectomy.

Abstract: Introduction Preoperative staging of bladder cancer using imaging methods has serious limitations. The accuracy of the abdominal diffusion-weighted magnetic resonance (DW-MRI) to predict residual muscle invasion, perivesical and/or lymph node affectation in the cystectomy specimen is evaluated. Material and methods A prospective study was performed on 20 patients with high grade muscle invasive bladder cancer who received transurethral resection of the bladder (TURB) in a period of S ), specificity (sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Ac) of the test were analyzed. The medians of the apparent diffusion coefficient (ADC) value (Mann–Whitney) were compared and the ROC curves study for DW-MRI and ADC was carried out. Results Distribution by categories was: pT0 1(5%), pT1 6(30%), pT2 2(10%), pT3 8(40%) and pT4 3(15%). There was an agreement in the T-pT assignment in 17(85%). In 7(35%) there was lymph node affectation (pN1-2). Consistency of the DW-MRI for muscle affectation was k = 0.89 (CI 0.67–1; S = 1.0, Sp = 0.86, PPV = 0.93, NPV = 1.0, Ac = 0.95), for perivesical fat affectation k = 0.6 (CI 0.25–0.95; S = 0.8, Sp = 0.8, PPV = 0.8, NPV = 0.8, Ac = 0.8) and for lymph node affectation k = 0.89 (CI 0.67–1; S = 0.86, Sp = 1.0, PPV = 1.0, NPV = 0.93, Ac = 0.95). Mean value of ADC was greater in G2 tumors (OMS1987) compared to G3 ( p = 0.08). Evaluation of DW-MRI imaging and ADC numerical value showed equivalent areas under the curve for muscle (0.93 and 0.9; Z = 0.7), fat (0.8 and 0.91; Z = 0.31) and lymph node (0.93 and 0.97; Z = 0.36) affectation, respectively. Conclusions DW-MRI allows for good pre-operative evaluation of the patient who is a candidate for cystectomy, especially for the prediction of muscle (

Evidencia disponible relativa a la eficacia de diferentes agentes endovesicales restituidores de glucosaminoglicanos empleados en cistitis intersticial

Abstract: Resumen Objetivos Comparacion de los diferentes regimenes terapeuticos endovesicales a base de agentes restituidores de glucosaminoglicanos (AR-GAG) comercialmente disponibles en Espana en terminos de efectividad clinica. Material y metodo Analisis bibliografico de los estudios publicados en Medline entre 1996 y 2012 sobre AR-GAG de aplicacion vesical con enfasis en los resultados clinicos. Comparacion post-hoc de la eficacia de dicho tratamiento en los estudios realizados en pacientes con cistitis intersticial en diferentes condiciones, mediante el calculo de los tamanos de efecto para el analisis de mejora en la escala analogica visual (EAV) de dolor y la tasa de respuesta clinica. Calculo del numero necesario de pacientes a tratar (NNT) para los distintos agentes a partir de la odds ratio (OR) e implicaciones economicas asociadas. Resultados La evidencia disponible es globalmente escasa. Un total de 38 articulos tratan de AR-GAG en diferentes indicaciones, 17 de ellos en cistitis intersticial y solamente 8 son subsidiarios de establecer comparacion entre los resultados presentados. Los tratamientos empleados fueron placebo, acido hialuronico de alto peso molecular al 0,8% (Cystistat®), condroitin sulfato sodico al 2% (Uracyst®) y una combinacion de acido hialuronico de bajo peso molecular al 1,6% mas condroitin sulfato al 2% (Ialuril®), entre 6 y 12 instilaciones. Otro preparado de acido hialuronico de bajo peso molecular (Uromac®) carece de evidencia cientifica alguna. Todos los elementos terapeuticos estudiados muestran disminucion de la puntuacion media de la EAV de dolor y aumento de la tasa de respuesta postratamiento. El NNT para los tratamientos estadisticamente ventajosos sobre placebo oscila entre 1,6 y 4,1. La comparacion post-hoc de las tasas de respuesta establece que Cystistat® 12 instilaciones (OR: 18,8; IC 95%: 6,4-57,2; p = 0,001) o 10 instilaciones (OR: 19,2; IC 95%: 5,3-75,3; p = 0,001) son las pautas de tratamiento que obtienen maxima efectividad. En ambos casos el NNT fue 1,6. Conclusiones Este estudio esta sujeto a multiples limitaciones inherentes a la naturaleza de su diseno; no obstante, muestra que, a pesar de que la literatura disponible es escasa, existen diferencias en cuanto a la efectividad clinica de los diferentes agentes y regimenes aplicados para el tratamiento endovesical de la cistitis intersticial. Estas diferencias conllevan tambien implicaciones de indole economica.

Clinical Efficacy of Intravitreal Injection of Dobesilate for Reversing Choroidal Angiogenesis in Age-Related Macular Degeneration

Abstract: Wet age-related macular degeneration is associated with chronic ischemia and inflammation that upregulate several inflammatory cytokines and growth factors, particularly vascular endothelial growth factor and fibroblast growth factor which promote the growth of choroidal neovascularization. Only with the introduction of drugs that directly inhibit the actions of vascular endothelial growth factor have ophthalmologists been able to offer patients with wet age-related macular degeneration reasonable hope for improvement of vision. However, intravitreal administration of anti-vascular endothelial growth factor drugs could be associated with unexpected ocular and systemic side effects. We present consecutive case series of 64 eyes of 64 patients with wet age-related macular degeneration treated with a single intravitreal injection of Dobesilate, a synthetic fibroblast growth factor inhibitor. The end points were the improvement from baseline visual acuity and normalization of retinal histology at 1 month. Intravitreal Dobesilate injection results in a significant improvement in functional and anatomic outcomes from the first month after injection. There were no cases of treatment-associated complications.

Case Report: Resolution of submacular haemorrhage secondary to exudative age-related macular degeneration after a single intravitreal dobesilate injection

Abstract: Introduction: Submacular haemorrhage is not an unusual cause of acute central vision loss, particularly in older people. It may be caused by a number of conditions, most common of which is exudative age-related madular degeneration. In patients affected by this type of macular degeneration, choroidal neovascularization extends into the subretinal space, producing substantial bleeding in approximately 17% of cases, resulting in large haemorrhages in the subretinal space that detach the neurosensory retina from the supporting retinal pigment epithelial (RPE) layer. This leads to substantial vision loss because of a relatively fast process of extensive photoreceptor atrophy in the overlying neuroretina and formation of macular scars Case presentation: We describe a patient with submacular haemorrhage secondary to exudative age-related macular degeneration, treated with intravitreal injection of dobesilate. Two months later, visual acuity in the treated eye reached 0.50 with a significant improvement of the distortion and an anatomical resolution of the haemorrhage, as confirmed by optical coherence tomography. Conclusions: Submacular haemorrhage secondary to exudative age-related macular degeneration can be successfully treated with intravitreal dobesilate. To our knowledge, this is the first case reporting a resolution of submacular haemorrhage after a single dobesilate injection.

The ejaculatory ducts and their implications in prostate adenocarcinoma.

Abstract: Objective To describe the histological characteristics of the ejaculatory duct and their importance in prostate adenocarcinoma. Study design Anatomical dissection of the prostate and seminal vesicles was performed in 20 autopsies of males without clinical evidence of prostatic pathology. Specimens were totally sampled to study the complete route of the ejaculatory ducts within the prostate, focusing specifically on the histological characteristics of the stroma enfolding the ducts. Results Ejaculatory ducts are covered by a distinct fibrous capsule that includes lymphatics and blood vessels with a specific spatial and architectural arrangement. Although easy to recognize in normal conditions, the positive nuclear immunostaining of epithelial cells with PAX-2 and PAX-8 may be of help to recognize the ejaculatory epithelium in problematic cases. These arteriolymphatic units made of hyalinized arteries and ectatic lymphatic vessels run parallel to the ejaculatory duct along its intraprostatic course and continue outside the prostate gland in the subadventitial tissue of seminal vesicles. Conclusion The ejaculatory ducts have a unique characteristic histology that allows its recognition in transrectal core biopsies. The issue matters in daily practice and may have prognostic implications in prostate adenocarcinoma since the invasion of this structure has been associated with a high percentage of extraprostatic disease.