Morphological and biochemical analysis of the secretory pathway in melanoma cells with distinct metastatic potential.

In this report, we have investigated whether alterations of the morphological and functional aspects of the biosecretory membrane system are associated with the metastatic potential of tumor cells. To this end, we have analyzed the morphology of the Golgi complex, the cytoskeleton organization and membrane trafficking steps of the secretory pathway in two human melanoma A375 cell line variants with low (A375-P) and high metastatic (A375-MM) potential. Immunofluorescence analysis showed that in A375-P cells, the Golgi complex showed a collapsed morphology. Conversely, in A375-MM cells, the Golgi complex presented a reticular and extended morphology. At the ultrastructural level, the Golgi complex of A375-P cells was fragmented and cisternae were swollen. When the cytoskeleton was analyzed, the microtubular network appeared normal in both cell variants, whereas actin stress fibers were largely absent in A375-P, but not in A375-MM cells. In addition, the F-actin content in A375-P cells was significantly lower than in A375-MM cells. These morphological differences in A375-P cells were accompanied by acceleration and an increase in the endoplasmic reticulum to Golgi and the trans-Golgi network to cell surface membrane transport, respectively. Our results indicate that in human A375 melanoma cells, metastatic potential correlates with a well-structured morphofunctional organization of the Golgi complex and actin cytoskeleton.

Functional dissociation between glucocorticoid-induced decrease in arachidonic acid release and inhibition of adrenocorticotropic hormone secretion in AtT-20 corticotrophs.

The biochemical basis of the short-term inhibitory effects of glucocorticoids on corticotropin release from pituitary corticotrophs is still obscure. A well-characterized effect of glucocorticoids in several cell types is the inhibition of arachidonic acid (AA) generation by phospholipase A2 (PLA2). Arachidonic acid and its metabolites have been implicated in the secretory process from a number of pituitary cells, such as the corticotrophs. We have thus examined the role of AA in the anti-secretagogue effects of glucocorticoids in a corticotropin-secreting clonal corticotroph line (AtT-20 D16/16). Glucocorticoids decreased AA release induced by melittin, a bee venom protein related to extracellular PLA2. When a possible role of AA in corticotropin release was studied, the following results were obtained: (a) all corticotropin secretagogues tested, including corticotropin-releasing factor (CRF), did not alter AA generation; (b) calcium and guanine nucleotides, which stimulate corticotropin release in permeabilized cells, inhibited the release of AA under the same conditions; (c) administration of melittin or of exogenous AA had no effect on basal and CRF-stimulated corticotropin release; (d) administration of large amounts of exogenous AA was unable to restore the ability to secrete corticotropin under suppression by glucocorticoids. Altogether, the data suggest that whereas glucocorticoids can inhibit both AA generation and corticotropin release, these two effects appear to be causally unrelated.

Neutrophil extracted lipocortin inhibits corticotropin secretion in the AtT-20 D16:16 clonal mouse pituitary cell line. Lipocortin inhibition of ACTH release in vitro.

The mechanism of short-term glucocorticoid (GC) inhibition of the hypothalamic-pituitary-adrenal axis is not well understood. The direct anti-inflammatory activities of lipocortins (LCs) have suggested a role for them as extra- and intracellular mediators of the biological effects of GCs. It has been reported that recombinant human (rh) LC1 inhibits corticotropin (ACTH) release from pituitary tissue in vitro but not from AtT-20 D16:16 corticotrophs. Using the same cell line we have tested whether other exogenous rhLCs or native LC extracted from polymorphonucleate neutrophils (neLC), likely LC1, have an effect on ACTH secretion. It is shown that: (1) basal release was not affected by a short-term incubation with neLC; (2) secretion induced by corticotropin-releasing factor (CRF) and other secretagogues (phorbol ester, potassium ion or calcium ionophore) was inhibited by neLC; (3) GC inhibition of CRF-stimulated release was reverted by a monoclonal anti-neLC antibody; (4) rhLC2, rhLC5 and the fragment 212-234 of rhLC5 were without effect. Thus, only neLC is effective on AtT-20 D16:16 cells, suggesting for this annexin a role in the early phase GC inhibition of ACTH secretion.

Cyclosporin A, but not FK506, increases arachidonic acid release and inhibits proliferation of pituitary corticotrope tumor cells.

The selective immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506) are used in the prevention of allogenic transplant rejection and in the therapy of chronic autoimmune inflammatory pathologies. Chronic treatment with CsA leads to secondary functional and trophic alterations of multiple organs and cell systems among which endocrine ones, through insofar uncharacterized mechanisms. With the recent use of FK506 there have been reports of an improved therapeutic efficacy and a reduction of side-effects, as compared to CsA. An intriguing hypothesis is that toxic damage could be due to a systemic CsA activation of arachidonic acid (AA) metabolism, through pathways as yet only partially characterized. The side-effects of both drugs have been poorly studied on cells from tissues other than blood or kidney. We have thus proceeded to study their action on AA release in corticotropic AtT-20/D16-16 cells. The results obtained are as follows: 1) during incubation times > or =12 h, basal AA release is increased by CsA, but not FK506; the acute effect (10 min) of melittin, a PLA2 activator, is significantly potentiated starting from a 30 min pretreatment with CsA but not FK506; manoalide, a PLA2 inhibitor, antagonizes the melittin potentiation of AA release by CsA whereas the inhibition of the melittin stimulus by glucocorticoids is antagonized both by CsA and FK506. 2) during longer (>2 d) incubation times, cell growth is inhibited by CsA but not FK506. These results indicate a role for CsA, not apparent for FK506, in the activation of PLA2 and in the inhibition of cell growth. They also suggest that CsA does not have a direct (i.e. not mediated by the immune system) therapeutic effect in inflammatory processes.

[Sudden death by sleep apnea syndrome associated with myxedema. A case report and a review of the literature]. / Morte improvvisa da sindrome delle apnee durante il sonno associata a mixedema. Presentazione di un caso e revisione della letteratura.

The case is presented of a 48-year old, slightly overweight, brachymorphic male affected by undiagnosed myxedema, admitted for nocturnal dyspnea present for several years but worsened in the last few weeks. At the age of 19, a paranoid schizophrenia diagnosis was indicated leading to repeated admissions to psychiatric hospitals and continued pharmacological therapy. His sensorium was lucid albeit with a slight psycho-motor slowing down; pharyngeal edema and macroglossia were also apparent, blood O2 saturation was 97%. After the first emergency exams, a hypothyroid condition associated with multinodular goiter and tracheal dislocation was found. Administration of triiodothyronine p.o. and hydrocortisone i.v. was thus initiated. In the doubt of sleep apnea syndrome (SAS) occurrence, pulse oximetry was performed, but after 7 hours, the patient suddenly deceased. Data showed waves of deep O2 desaturation secondary to periods of prolonged apnea. A literature review shows that such a case has never been reported. A posteriori analysis of the patient's clinical management indicates that the obstructive form of SAS, associated with myxedema is a condition which needs to be promptly diagnosed; due to the possible seriousness of its functional evolution, the need for intensive or sub-intensive therapy, with continuous nasal airway positive pressure or with oro-tracheal intubation and assisted ventilation, should be carefully taken into consideration; continuous cardiac monitoring should also be carried out, given the risk for acute coronary complications and ventricular arrhythmias in the early phases of substitutive therapy with thyroid hormone.

Ureteral endometriosis.

The authors present two cases of ureteral endometriosis. Urinary tract endometriosis has been frequently described affecting mainly the bladder. In the ureter, it is a rare pathology, of difficult identification. Treatment aims at ureteral disobstruction together with eradication of endometrial foci. This is accomplished by surgical, radiotherapeutic and chemotherapeutic means.

[An acute superior mediastinal syndrome with critical tracheal stenosis due to benign multinodular goiter complicated by intracystic hemorrhage]. / Sindrome mediastinica superiore acuta con stenosi tracheale critica da gozzo multinodulare benigno complicato da emorragia intracistica.

Large benign goiter with a cervical and intrathoracic retrotracheal location is uncommon, but troublesome, since it affects the upper mediastinum and usually causes dyspnea, dysphagia or vascular obstruction; on the other hand, a large mediastinal cyst of thyroid origin complicated by a massive, spontaneous hemorrhage is an exceptional event, implicating vital prognosis through an acute tracheal compression. A 45-year-old-man presented all these complications of a previously neglected nodular-cystic goiter, causing an acute respiratory distress. An emergency diagnosis and consequent surgery, in delayed urgency, were performed. This case is presented because of its rarity. Its clinic management is discussed, in the framework of the existing literature.

[Use of a polymeric gel to prevent retropulsion during intracorporeal lithotripsy]. / Uso de un gel polimérico para evitar retropulsión durante la litotricia intracorpórea.

INTRODUCTION: Stone retropulsion during ureteroscopic lithotripsy may lead to additional procedures needed for residual calculi. Several devices have been introduced in an attempt to reduce retropulsion. We set out to report our initial experience utilizing the new polymeric gel, BackStop. MATERIAL AND METHODS: We prospectively collected data on 7 ureteroscopy procedures with distal ureteral calculi treated with BackStop. Perioperative data including stone size, location, operative time, stone free rate, the presence or absence of retropulsion was collected. Success was defined as no residual fragments, no retropulsion, and no additional procedures required. RESULTS: All of the patients were rendered stone free after URS and no retropulsion occurred. There were no intraoperative complications nor gel migration or problems with dissolving the gel. CONCLUSIONS: BackStop is a new promising therapy to prevent retropulsion during ureteral intracorporeal lithotripsy. It is safe, easy to apply and very effective in preventing stone fragment migration. BackStop has the potential to reduce operative time.

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis.

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18 ± 3.38% and 2.35 ± 1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

[Prostate cancer: promising biomarkers related to aggressive disease]. / Cáncer de próstata: biomarcadores prometedores relacionados con la enfermedad agresiva.

BACKGROUND: Although a rapidly growing number of candidate biological markers of prognosis and/or response to specific treatments in prostate cancer, none have to date showed ability to completely prognosticate prostate cancer on evidence based urology. OBJECTIVE: To review the pertinent literature on the issue. ACQUISITION OF EVIDENCE: A comprehensive review of the current literature was done focusing on promising biomarkers related to aggressive prostate cancer. SUMMARY OF EVIDENCE: Combined with the heterogeneous nature of the disease, mixed case series are the most common study design, impeding robust results and the development of an effective therapeutic strategy. Improvement in prostate cancer patient survival requires not only the identification of new therapeutic target based on detailed understanding of the biological mechanisms involved in metastatic dissemination and tumor growth but strong clinical studies as well. CONCLUSION: Better study design involving potential markers and including well-classified and staged patients with robust methodology and adequate outcomes (mainly survival) are necessary to the field evolution.

[Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome?]. / Terapia de privación de andrógenos y obesidad mórbida: ¿tienenen común el riesgo cardiovascular por síndrome metabólico?

BACKGROUND: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.

[Extraperitoneal endoscopic radical prostatectomy: How steep is the learning curve? Overheads on the personal evolution technique in 5-years experience]. / Prostatectomía radical endoscópica extraperitoneal: ¿cuál es la pendiente de la curva de aprendizaje? Efectos en la técnica de evolución personal en una experiencia de 5 años.

OBJECTIVE: Prospectively investigate endoscopic extra peritoneal radical prostatectomy (EERP) learning curve impact on outcomes. MATERIALS AND METHODS: In a 5 year period (2004-2008) 270 patients underwent 5-6 ports laparoscopic radical prostatectomy at a referral center in Brazil. The initial 70 cases learning curve protocol included low body mass index patients with low volume, low grade prostate cancer. After that there were no criteria to exclude laparoscopic surgery. The patients were analyzed in two groups: Group 1, first 70 patients (30 transperitoneal and 40 extra peritoneal)-learning curve and Group 2, last 200 patients - EERP only. Surgical and outcome parameters were compared through Student's t test and Fisher's Exact Test. RESULTS: The mean age was 65 years (+/-8.2) and comparing Groups 1 and 2, mean operative time was 300 (+/-190) versus 180 (+/-100) minutes, blood loss 330 (+/-210) versus 210 (+/-180) mL, hospital stay 3 (2 to 5) versus 2 (1 to 3) days, positive surgical margins 15% versus 10%, erection sufficient to penetration in previous potent patients 73.3% versus 75%, respectively with no difference between groups. Overall, 78% of patients referred no previous impotence with groups' equivalence. Severe urinary incontinence, transfusion and complications rates were higher in group 1 (p<0.05): 10% versus 2%, 12% versus 2.25% and 30% versus 12.5%, respectively. Peritoneum perforation occurred in 40% and conversion to open surgery was not required. Nerve sparing procedure was applied in 85%. In 3.5-years mean follow-up 90% of patients were free of PSA recurrence with no difference between groups. CONCLUSION: Severe urinary incontinence, transfusion and complications rates are related to learning curve which is continuous, although a significant improvement is pragmatic after 70 cases. An intensive mentored training program should be considered to minimize the learning outlays.

A randomised, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia in Brazil.

Brazilian patients with benign prostatic hyperplasia were randomised in a 12-week, double-blind, double-dummy study to receive doxazosin gastrointestinal therapeutic system (GITS) 4 mg q.i.d. (n = 82) or tamsulosin 0.4 q.i.d. (n = 83). Primary endpoints were the absolute and percentage change from baseline in symptoms measured by International Prostate Symptom Score (IPSS). Secondary endpoints included IPSS, quality-of-life (QOL) question from the IPSS, and questions 6 and 7 of the Sexual Function Abbreviated Questionnaire (SFAQ) at weeks 4 and 12. Doxazosin GITS and tamsulosin improved IPSS with no significant differences between groups at week 12. During weeks 4-8, tamsulosin-treated patients demonstrated a slower improvement (p < 0.001) in IPSS than doxazosin GITS-treated patients. The proportion of satisfied patients was observed earlier with doxazosin GITS (p = 0.006) vs. tamsulosin. At week 12, the proportion of patients with little or no difficulty at ejaculation (Q6 of SFAQ) was higher in the doxazosin GITS group (p = 0.019). Both treatments were well tolerated.

Prostatectomía radical endoscópica extraperitoneal: ¿cuál es la pendiente de la curva de aprendizaje? Efectos en la técnica de evolución personal en una experiencia de 5 años / Extraperitoneal endoscopic radical prostatectomy: How steep is the learning curve? Overheads on the personal evolution technique in 5-years experience

Objetivo: Investigar prospectivamente los efectos de la curva de aprendizaje de la prostatectomía radical extraperitoneal endoscópica en sus resultados. Materiales y métodos: En un período de 5 años (2004–2008) se practicó prostatectomía radical laparoscópica con 5–6 puertos a 270 pacientes en un centro de referencia brasileño. En los primeros 70 casos, el protocolo de la curva de aprendizaje incluía a pacientes con índice de masa corporal bajo y cáncer de próstata de poco volumen y bajo grado. Posteriormente no se aplicaron criterios para descartar la cirugía laparoscópica. Se analizó a los pacientes en dos grupos: grupo 1, primeros 70 pacientes (30 transperitoneal y 40 extraperitoneal) —curva de aprendizaje—, y grupo 2, últimos 200 pacientes —sólo prostatectomía radical endoscópica extraperitoneal—. Los parámetros quirúrgicos y los resultados se compararon mediante la prueba de la t de Student y la prueba exacta de Fisher. Resultados: La media de edad fue de 65 años (± 8,2), y los parámetros determinados en los grupos 1 y 2, respectivamente, fueron los siguientes: tiempo quirúrgico medio, 300 (±190) y 180 (±100) min; pérdida de sangre, 330 (±210) y 210 (±180)ml; estancia hospitalaria, 3 (2–5) y 2 (1–3) días; márgenes quirúrgicos positivos, el 15 y el 10%; erección suficiente para la penetración en pacientes previamente potentes, el 73,3 y el 75%, sin diferencia entre los grupos. El 78% de los pacientes de ambos grupos no informó de impotencia previa. Las tasas de incontinencia urinaria grave, transfusión y complicaciones fueron mayores en el grupo 1 (p<0,05): el 10 frente al 2%, el 12 frente al 2,25% y el 30 frente al 12,5%, respectivamente. Se produjo perforación del peritoneo en el 40% de los pacientes y no se precisó conversión a cirugía abierta en ningún caso. En el 85% de los casos se utilizó un procedimiento de preservación de nervios. Tras un seguimiento medio de 3,5 años, el 90% de los pacientes no mostró recidiva del PSA, sin que hubiera diferencia entre los grupos. Conclusión: Las tasas de incontinencia urinaria grave, transfusión y complicaciones están relacionadas con la curva de aprendizaje, que es continua, aunque se hace evidente una mejoría importante después de 70 casos. Debe considerarse la aplicación de un programa de formación intensivo supervisado para limitar los problemas del aprendizaje (AU)

Objective: Prospectively investigate endoscopic extra peritoneal radical prostatectomy (EERP) learning curve impact on outcomes. Materials and methods: In a 5 year period (2004–2008) 270 patients underwent 5–6 ports laparoscopic radical prostatectomy at a referral center in Brazil. The initial 70 cases learning curve protocol included low body mass index patients with low volume, low grade prostate cancer. After that there were no criteria to exclude laparoscopic surgery. The patients were analyzed in two groups: Group 1, first 70 patients (30 transperitoneal and 40 extra peritoneal)—learning curve and Group 2, last 200 patients - EERP only. Surgical and outcome parameters were compared through Student's t test and Fisher's Exact Test. Results: The mean age was 65 years (±8.2) and comparing Groups 1 and 2, mean operative time was 300 (±190) versus 180 (±100) minutes, blood loss 330 (±210) versus 210 (±180) mL, hospital stay 3 (2 to 5) versus 2 (1 to 3) days, positive surgical margins 15% versus 10%, erection sufficient to penetration in previous potent patients 73.3% versus 75%, respectively with no difference between groups. Overall, 78% of patients referred no previous impotence with groups’ equivalence. Severe urinary incontinence, transfusion and complications rates were higher in group 1 (p<0.05): 10% versus 2%, 12% versus 2.25% and 30% versus 12.5%, respectively. Peritoneum perforation occurred in 40% and conversion to open surgery was not required. Nerve sparing procedure was applied in 85%. In 3.5-years mean follow-up 90% of patients were free of PSA recurrence with no difference between groups. Conclusion: Severe urinary incontinence, transfusion and complications rates are related to learning curve which is continuous, although a significant improvement is pragmatic after 70 cases. An intensive mentored training program should be considered to minimize the learning outlays (AU)

[Treatment of male sterility (author's transl)]. / Tratamento da esterilidade masculina

In 330 cases of male sterility, the authors found in the seminal fluid 270 cases of quantitative alteration, 196 of qualitative alteration, 62 cases with biochemical disturbances and 122 patients with infections. After the specific treatment of these patients, the result was that 50 to 58.2% of them presented response for the quantitative, qualitative and biochemical alterations. In the infections, the index obtained was 85.2%. Among these 330 cases, they were obtained 73 cases of pregnancy (22.1%) with eight cases of abortion(10.9%).

[Percutaneous treatment of varicocele: technical considerations and limitations of the method]. / Tratamento percutâneo da varicocele: considerações técnicas e limitações do método.

Three cases of varicocele were treated with good results by selective embolization of the spermatic vein. The technique of the procedure is discussed.

Synchronous bilateral carcinoma of the adrenal gland: 2 case reports.

The existence of synchronous bilateral adrenal masses is an uncommon condition except in the relatively more frequent cases of pheochromocytoma or metastatic tumors. Two cases of synchronous nonfunctioning bilateral adrenal cortex carcinoma, removed during the same operation, are described. The patients currently are receiving hormonal supplementation, and were well 16 and 12 months postoperatively.

Uso de un gel polimérico para evitar retropulsión durante la litotricia intracorpórea / Use of a Polymeric Gel to Prevent Retropulsion During Intracorporeal Lithotripsy

Introducción: La retropulsión de los cálculos durante la litotricia ureteroscópica puede conducir a procedimientos adicionales necesarios para los cálculos residuales. Se han introducido varios dispositivos en un intento de reducir la retropulsión. Nos pusimos en marcha para informar de nuestra experiencia inicial al utilizar el nuevo gel polimérico BackStop®. Material y métodos: Hemos recogido de forma prospectiva los datos sobre 7 procedimientos de ureteroscopia con cálculos ureterales distales tratados con BackStop®. Se recogieron los datos perioperatorios, tales como tamaño del cálculo, ubicación, tiempo quirúrgico, tasa libre de cálculo, presencia o ausencia de retropulsión. El éxito se definió como la ausencia de fragmentos residuales, de retropulsión y de procedimientos adicionales que se requieren. Resultados: Todos los pacientes quedaron libres de litiasis tras la URS y no se produjo ninguna retropulsión. No hubo complicaciones intraoperatorias ni migración de gel o problemas con la disolución del gel. Conclusiones: BackStop® es un nuevo tratamiento prometedor para prevenir la retropulsión durante la litotricia intracorpórea ureteral. Es seguro, fácil de aplicar y muy eficaz en la prevención de la migración de fragmentos de cálculos. Backstop® tiene el potencial para reducir el tiempo quirúrgico (AU)

Introduction: Stone retropulsion during ureteroscopic lithotripsy may lead to additional procedures needed for residual calculi. Several devices have been introduced in an attempt to reduce retropulsion. We set out to report our initial experience utilizing the new polymeric gel, BackStop®. Material and methods: We prospectively collected data on 7 ureteroscopy procedures with distal ureteral calculi treated with BackStop®. Perioperative data including stone size, location, operative time, stone free rate, the presence or absence of retropulsion was collected. Success was defined as no residual fragments, no retropulsion, and no additional procedures required. Results: All of the patients were rendered stone free after URS and no retropulsion occurred. There were no intraoperative complications nor gel migration or problems with dissolving the gel. Conclusions: BackStop® is a new promising therapy to prevent retropulsion during ureteral intracorporeal lithotripsy. It is safe, easy to apply and very effective in preventing stone fragment migration. BackStop® has the potential to reduce operative time (AU)

Cáncer de próstata: biomarcadores prometedores relacionados con la enfermedad agresiva / Prostate Cancer: Promising Biomarkers Related to Aggressive Disease

Antecedentes: A pesar del número rápidamente creciente de marcadores biológicos de pronóstico y/o respuesta a tratamientos específicos posibles en el cáncer de próstata, ninguno ha mostrado hasta la fecha la capacidad de pronosticar por completo el cáncer de próstata en la urología basada en la evidencia. Objetivo: Revisar la literatura pertinente sobre el tema. Adquisición de evidencia: Se llevó a cabo una revisión exhaustiva de la literatura actual centrándose en los prometedores biomarcadores relacionados con el cáncer de próstata agresivo. Resumen de la evidencia: En combinación con la naturaleza heterogénea de la enfermedad, las series de casos mixtas son el diseño de estudio más común, que impiden resultados sólidos y el desarrollo de una estrategia terapéutica eficaz. La mejora de la supervivencia del paciente con cáncer de próstata requiere no solo la identificación de un nuevo objetivo terapéutico, basado en la comprensión detallada de los mecanismos biológicos implicados en la diseminación metastásica y el crecimiento del tumor, sino también consistentes estudios clínicos. Conclusión: Se necesita un mejor diseño de estudio implicando los marcadores potenciales e incluyendo a los pacientes bien clasificados y por estadios, con una metodología sólida y los resultados adecuados (sobre todo la supervivencia) para la evolución en este campo (AU)

Background: Although a rapidly growing number of candidate biological markers of prognosis and/or response to specific treatments in prostate cancer, none have to date showed ability to completely prognosticate prostate cancer on evidence based urology. Objective: To review the pertinent literature on the issue. Acquisition of evidence: A comprehensive review of the current literature was done focusing on promising biomarkers related to aggressive prostate cancer. Summary of evidence: Combined with the heterogeneous nature of the disease, mixt case series are the most common study design, impeding robust results and the development of an effective therapeutic strategy. Improvement in prostate cancer patient survival requires not only the identification of new therapeutic target based on detailed understanding of the biological mechanisms involved in metastatic dissemination and tumor growth but strong clinical studies as well. Conclusion: Better study design involving potential markers and including well-classified and staged patients with robust methodology and adequate outcomes (mainly survival) are necessary to the field evolution (AU)