Experiencia inicial del uso de SelectMDx(R) en el diagnóstico de cáncer de próstata en un entorno de práctica clínica habitual «real-world evidence» / Initial experience with SelectMDx(R) in the diagnosis of prostate cancer in a real-world evidence clinical practice setting

INTRODUCCIÓN: El uso de biomarcadores en la detección del cáncer de próstata (CP) puede disminuir el sobrediagnóstico y sobretratamiento de CP no significativos. Analizamos la utilidad y aplicabilidad del marcador SelectMDx® en un entorno de práctica clínica habitual. MATERIAL Y MÉTODOS: Estudio retrospectivo de 48 pacientes evaluados mediante el test SelectMDx® entre julio de 2017 y abril de 2019. Los pacientes se estratificaron en dos grupos según el riesgo estimado por el test de CP clínicamente significativo (CP-CS): < 2% o «muy bajo riesgo», y > 2%. Los resultados se expresaron en función de los antecedentes de biopsia prostática (BP) y resonancia magnética multiparamétrica (RMmp). RESULTADOS: En pacientes con BP negativa y RMmp normal/dudosa el riesgo fue < 2% en 7/9 casos. En pacientes sin BP y RMmp normal/dudosa el riesgo fue < 2% en 12/18 casos, y 2/6 casos con un riesgo % presentaron un CP-CS. De los 14 pacientes sin BP ni RMmp previas, 9 presentaron un riesgo < 2%, con 2 casos diagnosticados de CP en los 5 pacientes con riesgo > 2%. En el resto de subgrupos el número de pacientes es pequeño como para poder extraer conclusiones. En todos los casos con tacto rectal patológico el test demostraba un riesgo de padecer CP > 2%. CONCLUSIÓN: SelectMDx® es un test prometedor para detectar pacientes con un riesgo muy bajo de CP-CS, especialmente en pacientes con sospecha de CP con o sin BP negativas, en los que la RMmp muestre un resultado normal/dudoso. La presencia de un tacto rectal patológico puede condicionar el resultado del test

INTRODUCTION: The use of biomarkers in the detection of prostate cancer (PC) can decrease overdiagnosis and overtreatment of non-significant PC. We analyze the usefulness and applicability of the SelectMDx® marker in a routine clinical practice setting. MATERIAL AND METHODS: Retrospective study of 48 patients evaluated by the SelectMDx® test between July 2017 and April 2019. Patients were stratified into two groups according to the risk estimated by the clinically significant CP test (CS-PC): < 2% or 'very low risk', and > 2%. Results were expressed based on previous prostate biopsy (PB) and multi-parametric magnetic resonance imaging (mpMRI) outcomes. RESULTS: Patients with negative PB and normal/doubtful mpMRI had < 2% risk in 7/9 cases. Patients without PB and normal/doubtful mpMRI had < 2% risk in 12/18 cases, and 2/6 cases with a > 2% risk presented CS-PC. Of the 14 patients with no previous PB or mpMRI, 9 had < 2% risk, and 2 cases were diagnosed with PC from the group of patients (5) with risk >2%. The number of patients in the remaining subgroups is too small to draw any conclusions. In all cases with pathological digital rectal examination, the test showed a > 2% PC risk. CONCLUSION: SelectMDx® is a promising test for detecting patients with a very low risk of CS-PC, especially in patients with suspected PC, with or without negative PB, with normal/doubtful mpMRI. The presence of a pathological digital rectal examination may condition the result of the test

Initial experience with SelectMDx® in the diagnosis of prostate cancer in a real-world evidence clinical practice setting. / Experiencia inicial del uso de SelectMDx® en el diagnóstico de cáncer de próstata en un entorno de práctica clínica habitual «real-world evidence¼.

INTRODUCTION: The use of biomarkers in the detection of prostate cancer (PC) can decrease overdiagnosis and overtreatment of non-significant PC. We analyze the usefulness and applicability of the SelectMDx® marker in a routine clinical practice setting. MATERIAL AND METHODS: Retrospective study of 48 patients evaluated by the SelectMDx® test between July 2017 and April 2019. Patients were stratified into two groups according to the risk estimated by the clinically significant CP test (CS-PC): <2% or 'very low risk', and >2%. Results were expressed based on previous prostate biopsy (PB) and multi-parametric magnetic resonance imaging (mpMRI) outcomes. RESULTS: Patients with negative PB and normal/doubtful mpMRI had <2% risk in 7/9 cases. Patients without PB and normal/doubtful mpMRI had <2% risk in 12/18 cases, and 2/6 cases with a >2% risk presented CS-PC. Of the 14 patients with no previous PB or mpMRI, 9 had <2% risk, and 2 cases were diagnosed with PC from the group of patients (5) with risk >2%. The number of patients in the remaining subgroups is too small to draw any conclusions. In all cases with pathological digital rectal examination, the test showed a >2% PC risk. CONCLUSION: SelectMDx® is a promising test for detecting patients with a very low risk of CS-PC, especially in patients with suspected PC, with or without negative PB, with normal/doubtful mpMRI. The presence of a pathological digital rectal examination may condition the result of the test.

Comentario a: «Expresión aumentada del factor inducible por hipoxia 1 alfa y del factor de crecimiento del tejido conectivo acompañando a fibrosis en testículos de ratas con varicocele» / Comment to: «Increased Expression of Hypoxia-Inducible Factor-1alfa and Connective Tissue Growth Factor Accompanied by Fibrosis in the Rat Testis of Varicocele»

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Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients.

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events (AU)

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Uso de prótesis en urología / Use of prosthesis in Urology

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The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil.

We investigated the potency and the selectivity profile of vardenafil on phosphodiesterase (PDEs) enzymes, its ability to modify cGMP metabolism and cause relaxation of penile smooth muscle and its effect on erections in vivo under conditions of exogenous nitric oxide (NO) stimulation. PDE isozymes were extracted and purified from human platelets (PDE5) or bovine sources (PDEs 1, 2, 3, 4 and 6). The inhibition of these PDEs and of human recombinant PDEs by vardenafil was determined. The ability to potentiate NO-mediated relaxation and influence cGMP levels in human corpus cavernosum strips was measured in vitro, and erection-inducing activity was demonstrated in conscious rabbits after oral administration together with intravenous doses of sodium nitroprusside (SNP). The effects of vardenafil were compared with those of the well-recognized PDE5 inhibitor, sildenafil (values for sildenafil in brackets). Vardenafil specifically inhibited the hydrolysis of cGMP by PDE5 with an IC50 of 0.7 nM (6.6 nM). In contrast, the IC50 of vardenafil for PDE1 was 180 nM; for PDE6, 11 nM; for PDE2, PDE3 and PDE4, more than 1000 nM. Relative to PDE5, the ratios of the IC50 for PDE1 were 257 (60), for PDE6 16 (7.4). Vardenafil significantly enhanced the SNP-induced relaxation of human trabecular smooth muscle at 3 nM (10 nM). Vardenafil also significantly potentiated both ACh-induced and transmural electrical stimulation-induced relaxation of trabecular smooth muscle. The minimum concentration of vardenafil that significantly potentiated SNP-induced cGMP accumulation was 3 nM (30 nM). In vivo studies in rabbits showed that orally administered vardenafil dose-dependently potentiated erectile responses to intravenously administered SNP. The minimal effective dose that significantly potentiated erection was 0.1 mg/kg (1 mg/kg). The selectivity for PDE5, the potentiation of NO-induced relaxation and cGMP accumulation in human trabecular smooth muscle and the ability to enhance NO-induced erection in vivo indicate that vardenafil has the appropriate properties to be a potential compound for the treatment of erectile dysfunction. Vardenafil was more potent and selective than sildenafil on its inhibitory activity on PDE5.

Rationale for the combination of PGE(1) and S-nitroso-glutathione to induce relaxation of human penile smooth muscle.

Many men with erectile dysfunction have been successfully treated with intracavernosal injection of prostaglandin E(1) (PGE(1)) but this treatment is ineffective in 30 to 40% of patients. The goals of this study were to characterize PGE(1)-induced relaxation of isolated human penile smooth muscle (penile arteries and trabecular strips), correlating this in vitro response with the clinical response to this drug, and to evaluate the effects of the combination of PGE(1) with S-nitrosoglutathione (SNO-Glu) on relaxation of isolated human penile smooth muscle. Large variability in the EC(50) and maximal relaxation induced by PGE(1) was observed between tissues of different patients. Patients with poor clinical response to intracavernosal alprostadil (PGE(1)) had significantly larger EC(50) values and smaller maximal relaxation compared with patients with partial or complete clinical response to this drug. SNO-Glu consistently produced complete or near complete relaxation of human corpus cavernosum strips and penile arteries, even when the tissue responded poorly to PGE(1). In trabecular strips, the combination of PGE(1) and SNO-Glu in a 1:100 ratio demonstrated a synergistic relaxation effect. The combination of PGE(1) and SNO-Glu simultaneously increased the levels of both cAMP and cGMP in human corpus cavernosum tissue. Our results suggest that the clinical effectiveness of intracavernosal administration of PGE(1) is related to the variability of the relaxation responses of human trabecular tissue and penile arteries to this drug. The synergistic interaction of PGE(1) and SNO-Glu makes this combination an effective method to cause penile smooth muscle relaxation, a necessary step to initiate and maintain penile erection.

[Myxoid neurofibroma of the renal sinus]. / Neurofibroma mixoide del seno renal.

Presentation of one case of a 7.5 x 6 cm myxoid neurofibroma located in the left renal sinus, which is really exceptional. The finding in a 41-year-old, asymptomatic patient is casual and during a routine follow-up study with ultrasound for a Hodgkin lymphoma with a 9-year remission interval. Computerized axial tomography, intravenous urography and thin-needle puncture-aspiration cytology were performed to investigate its origin. Treatment is surgical and requires nephrectomy of the affected side.

[A program of intracavernous drug-induced erection for the treatment of impotence]. / Programa de erección farmacológica intracavernosa para el tratamiento de la impotencia.

The study includes 138 patients with erectile dysfunction, all of them previously treated with intracavernous injections. Following study and classification of the type of impotence, they were all included in one of the four following groups. The drugs used were, in group I (73 patients) Prostaglandins E1, in group II (37 patients) Papaverine, in group III (6 patients) a combination of Papaverine and Phentolamine and in group IV (22 patients) a combination of Papaverine and Prostaglandins E1. We found a good treatment response in 59.3% cases (60.3% in group I, 51.3% in group II, 66.7% in group III, and 69% in group IV). We outline the better results obtained in group IV, as well as the reduced number of complications in our series.

[Unilateral essential hematuria: diagnostic and therapeutic attitude in 2 cases]. / Hematuria esencial unilateral: actitud diagnóstica y terapéutica en dos casos.

Unilateral essential haematuria is an unusual clinical entity where diagnosis is achieved by exclusion of other urological and nephrological conditions. The paper reports two female patients with unilateral anaemic macroscopic haematuria which were evaluated using flexible ureteropyeloscopy, and one also underwent percutaneous pyeloscopy. In one of the patients a renal papilla haemangioma was found which was fulgurated, while the lesion was not identified in the other patient, although neither of them has shown haematuria recurrence during the follow-up period. The authors believe that uretororrenoscopy and percutaneous nephroscopy should be considered in selected patients with unilateral essential haematuria due to its diagnostic and therapeutic possibilities.

[Infiltrating transitional carcinoma of the bladder (I). Comparison of 2 groups treated with preoperative radiotherapy (long-term protocol and short-term protocol) + radical cystectomy versus radical cystectomy only. Analysis of local recurrence and metastasis]. / Carcinoma transicional infiltrante de vejiga. (1a parte). Comparación de 2 grupos tratados con radioterapia preoperatoria (pauta larga y pauta corta) + cistectomía radical con otro manejado con cistectomía radical solo. Análisis de recidiva local y metástasis.

We analyze our experience in 175 patients with transitional bladder cancer for whom radical cystectomy was indicated. Patients were divided into three groups: one group was managed with radical cystectomy only and the other two with pre-operative radiotherapy: long-term approach and short-term approach. No significant differences have been observed when comparing current survival rate and disease-free intervals of all three groups. It can be deduced from our series that, by the scarce number of local recurrences observed, there is no other measure to be added to surgery directed to improve the tumour's local management. Most metastasis were diagnosed within 18 months after cystectomy. 58.4% patients presented bone dissemination. The risk of distant dissemination increases with the extent of vesical wall invasion, degree of anaplasia and presence of positive glands. The gland stage is not necessary for the metastasis to be present. Death's ratio with distant dissemination is significantly lower in the group managed Without pre-operative radiotherapy than in the others. Of the 11 patients where no tumour was observed in the cystectomy piece, 2 developed metastasis, indicating that this was already present before bladder extraction. Management of patients with infiltrating++ bladder cancer is complex, but no efforts should be spared to advise the most appropriate approach for each particular case. Chemotherapy plays an unquestionable role among the procedures we have to control, since most patients' deaths happen within two years after local-regional treatment of the primitive tumour and nearly all of them as a consequence of metastasis. Cytostatic agents are the only effective therapy for distant dissemination. We believe that every patient with a cancer extended to the perivesical fat or with dissemination to regional glands, whichever the stage, should be treated with chemotherapy after extirpation of the bladder, and starting as early as the patient's general status would allow it.

Cavernosography in diagnosis of metastatic tumors of the penis: 5 new cases and a review of the literature.

Secondary tumors of the penis are rare, with 266 cases having been reported. We describe 5 new cases studied by cavernosography. The primary tumors were bladder cancer in 3 patients and prostatic cancer in 2. Cavernosography suggested the diagnosis, which was confirmed by a guided biopsy or fine needle aspiration biopsy. The prognosis has been poor, with the average survival being less than 9 months.