Staff lens doses in interventional urology. A comparison with interventional radiology, cardiology and vascular surgery values.

The purpose of this work is to evaluate radiation doses to the lens of urologists during interventional procedures and to compare them with values measured during interventional radiology, cardiology and vascular surgery. The measurements were carried out in a surgical theatre using a mobile C-arm system and electronic occupational dosimeters (worn over the lead apron). Patient and staff dose measurements were collected in a sample of 34 urology interventions (nephrolithotomies). The same dosimetry system was used in other medical specialties for comparison purposes. Median and 3rd quartile values for urology procedures were: patient doses 30 and 40 Gy cm(2); personal dose equivalent Hp(10) over the apron (µSv/procedure): 393 and 848 (for urologists); 21 and 39 (for nurses). Median values of over apron dose per procedure for urologists resulted 18.7 times higher than those measured for radiologists and cardiologists working with proper protection (using ceiling suspended screens) in catheterisation laboratories, and 4.2 times higher than the values measured for vascular surgeons at the same hospital. Comparison with passive dosimeters worn near the eyes suggests that dosimeters worn over the apron could be a reasonable conservative estimate for ocular doses for interventional urology. Authors recommend that at least the main surgeon uses protective eyewear during interventional urology procedures.

El aprendizaje de la nefrolitectomía percutánea en posición supina. Estudio observacional multicéntrico / Learning of percutaneous nephrolithotomy in supine position. An observational multicenter study

Objetivo: Estudiar prospectivamente los resultados operatorios y las complicaciones de la nefrolitectomía percutánea (NLP) en posición supina para valorar la dificultad de su aprendizaje y cómo afecta la experiencia a los resultados. Establecer una comparación relativa con los datos publicados en la literatura acerca de la posición en prono. Material y métodos: Estudio prospectivo observacional multicéntrico sobre NLP en posición de Valdivia o en su variante de Galdácano. Se recogen variables demográficas y variables específicas dependientes de la litiasis. Se valoran aspectos técnicos, tiempo quirúrgico, tasa de éxito y complicaciones según la clasificación de Clavien-Dindo. Resultados: Desde septiembre de 2008 a junio de 2011 se han registrado 335 NLP en posición supina realizadas en 13 centros españoles. La proporción hombre/mujer fue 1:1,28 y la edad media 51,3 + 14,5 años; 211 (63%) casos fueron realizados por urólogos con experiencia de > 50 casos y 124 (37%) por urólogos con menos experiencia. El tiempo operatorio medio fue 113,3±46,4min, 106,6±38,2 en experimentados vs. 124,9±56,2 en noveles (p<0,002). No se detectó diferencia en el tamaño medio de la litiasis, pero en el grupo con experiencia se trató una mayor proporción de casos coraliformes y de litiasis múltiples que en el grupo novel (p<0,001). La tasa de éxito evaluada como ausencia total de restos litiásicos fue 69,6%, sin diferencias entre grupos (68,2 vs. 71,8%). En 102 (30,6%) pacientes hubo litiasis residual, precisando tratamiento complementario 60 (17,9%). La tasa relativa de éxito global fue 82,1% y la tasa de complicaciones 25,4%, sin detectarse diferencias entre grupos. No obstante, el grupo novel presentó mayor número de complicaciones mayores (p>0,001). Conclusión: La NLP en supino está teniendo una rápida y consolidada difusión en nuestro entorno, y su efectividad y seguridad parece equivalente a la descrita en la literatura para la NLP en prono. Resulta posible conseguir buenos resultados con una modesta curva de aprendizaje. La tasa de complicaciones mayores asociadas al procedimiento disminuye con la experiencia (AU)

Objective: To prospectively study the post-operative results and complications of percutaneous nephrolithotomy (PNL) in supine position to assess difficulty of learning it and how experience affects the results. To establish a relative comparison with the data published in the literature on the prone position. Material and methods: A prospective observational multicenter study on PNL in Valdivia position or in its Galdakao variant was performed. Demographic variables and specific variables related to the lithiasis were collected. Technical aspects, surgery time, success rate and complications according to the Clavien-Dindo classifications were assessed. Results: A total of 335 PNL in supine position conducted in 13 Spanish centers were registered from September 2008 to June 2011. The man: woman ratio was 1:1.28 and mean age 51.3 + 14.5 years. 211 (63%) cases were performed by urologists with experience in > 50 cases and 124 (37%) by urologists with less experience. Mean operation time was 113.3±46.4min, 106.6±38.2 for the experienced ones vs. 124.9±56.2 in the novice ones (P<0.002). No difference was detected in the mean size of the lithiasis. However, in the experienced group, there was a greater proportion of coraliform cases and multiple lithiasis than in the novice group (P<0.001). Success rate evaluated as total absence of lithiasic residuals was 69.6%, without differences between groups (68.2 vs. 71.8%). In 102 (30.6%) patient had residual lithiasis and 60 (17,9%) required complementary treatment. Relative global success rate was 82.1% and complications rate 25.4%, without detecting differences between groups. However, the novel group had more major complications (P>0.001). Conclusion: The PNL in supine position is obtaining rapid and consolidated diffusion in our setting and its effectiveness and safety seems to be equivalent to that described in the literature for PNL in prone position. It is possible to obtain good results with a modest learning curve. The rate of greater complications associated to the procedure decreases with experience (AU)

[Learning of percutaneous nephrolithotomy in supine position. An observational multicenter study]. / El aprendizaje de la nefrolitectomía percutánea en posición supina. Estudio observacional multicéntrico.

OBJECTIVE: To prospectively study the post-operative results and complications of percutaneous nephrolithotomy (PNL) in supine position to assess difficulty of learning it and how experience affects the results. To establish a relative comparison with the data published in the literature on the prone position. MATERIAL AND METHODS: A prospective observational multicenter study on PNL in Valdivia position or in its Galdakao variant was performed. Demographic variables and specific variables related to the lithiasis were collected. Technical aspects, surgery time, success rate and complications according to the Clavien-Dindo classifications were assessed. RESULTS: A total of 335 PNL in supine position conducted in 13 Spanish centers were registered from September 2008 to June 2011. The man:woman ratio was 1:1.28 and mean age 51.3+14.5 years. 211 (63%) cases were performed by urologists with experience in >50 cases and 124 (37%) by urologists with less experience. Mean operation time was 113.3 ± 46.4 min, 106.6 ± 38.2 for the experienced ones vs. 124.9 ± 56.2 in the novice ones (P<.002). No difference was detected in the mean size of the lithiasis. However, in the experienced group, there was a greater proportion of coraliform cases and multiple lithiasis than in the novice group (P<.001). Success rate evaluated as total absence of lithiasic residuals was 69.6%, without differences between groups (68.2 vs. 71.8%). In 102 (30.6%) patient had residual lithiasis and 60 (17,9%) required complementary treatment. Relative global success rate was 82.1% and complications rate 25.4%, without detecting differences between groups. However, the novel group had more major complications (P>.001). CONCLUSION: The PNL in supine position is obtaining rapid and consolidated diffusion in our setting and its effectiveness and safety seems to be equivalent to that described in the literature for PNL in prone position. It is possible to obtain good results with a modest learning curve. The rate of greater complications associated to the procedure decreases with experience.

Loss of heterozygosity and methylation of p16 in renal cell carcinoma.

To investigate the possible role of genomic aberrations of chromosome 9p21 in the tumorigenesis of human renal cell carcinoma (RCC), 40 sporadic RCCs were studied using PCR analyses. The tumours were predominantly low stage and low grade. Loss of heterozygosity (LOH) was observed in nine of 39 informative cases, but no homozygous deletion was noticed. Hypermethylation of the promoter region of p16 occurred in eight of the 40 RCCs. No correlation was found between hypermethylation of the p16 gene and LOH on 9p21. A similar level of LOH and methylation was observed in the 40 RCCS regardless of histology, grade and stage. These results suggest that inactivation of p16 and the possibility of other unknown tumour suppressor genes located on other chromosomes could be involved in the pathogenesis of RCC.

Long-term follow-up of a randomized prospective trial comparing a standard 81 mg dose of intravesical bacille Calmette-Guérin with a reduced dose of 27 mg in superficial bladder cancer.

OBJECTIVES: To determine the efficacy of a three-fold reduced dose (RD, 27 mg) of intravesical bacille Calmette-Guérin (BCG) against the standard dose (81 mg) in patients with superficial bladder cancer, assessing recurrence, progression and differences in toxicity. PATIENTS AND METHODS: Five hundred patients with superficial bladder cancer (Ta, T1, Tis) were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG Connaught strain (weekly x six and thereafter fortnightly x six) either with the standard or RD instillation. RESULTS: All but one of the 500 patients were evaluable for efficacy and toxicity (252 in the standard arm and 247 in the RD arm). The median follow-up was 69 months (maximum 104); 71 (28%) patients in the standard arm and 76 (31%) in the RD arm developed recurrences; the median time to recurrence has not yet been attained, but at 5 years the mean (sd) percentage of recurrence-free patients was 70.5 (3.12) and 70.4 (3.1) for the standard and RD arms, respectively. In patients presenting with multifocal tumours, the standard dose was more effective against recurrences than the RD (P=0.0151). In those with G3 and high-risk tumours overall, the superiority of the standard dose was marginal (P=0.060 and P=0.082). Twenty-nine (11.5%) tumours in the standard arm and 33 (13.3%) in the RD arm progressed to invasive disease; the median time to progression has not yet been attained, but the percentage of progression-free patients at 5 years was 88.8 (2.23) and 86.9 (2.31) for the standard and RD arms, respectively. The standard dose was more effective than the RD against progression only in patients with multifocal disease (P=0.048). Twelve (4.8%) cystectomies were performed in the standard and 15 (6.1%) in the RD arm. Currently, 106 (21.2%) patients have died, but only 38 (7.6%) from bladder cancer, i.e. 20 (7.9%) in the standard and 18 (7.5%) in RD arm. Overall the disease-specific death rate was lower for those patients who completed the scheduled treatment. The cause-specific survival at 5 years did not differ between the arms (P=0.76) but there was a trend toward better cause-specific survival for patients with multifocal tumours in the standard arm. Toxicity differed between the arms, significantly more patients having no toxicity in the RD arm, and fewer having delayed instillations or withdrawing. However, severe systemic toxicity occurred even in patients treated with the RD, in a similar proportion to those receiving the standard dose. CONCLUSION: Overall, the RD gave similar results for recurrence and progression but with significantly less toxicity. However, patients with multifocal tumours fared better with the standard dose and there was a trend towards better recurrence rates in patients with high-risk tumours. We recommend continuing to use the standard dose for high-risk tumours, while we consider the reduced dose safe and effective for intermediate-risk lesions and for maintenance schedules.

Loss of heterozygosity on the short arm of chromosome 3 in renal cancer.

3% of human cancers are renal cell carcinomas (RCC). The most common chromosome abnormality found in this tumor is loss of heterozygosity (LOH) on the short arm of chromosome 3, which suggests that there must be one or more tumor suppressor genes between 3p14 and 3p21 near the VHL gene which play a relevant role in renal cancer development. DNA from normal and tumor tissue from 40 patients at various stages of RCC was analyzed for LOH at three microsatellites mapped to 3p (3p14.1-14.3; 3p21.2-21.3 and 3p25) by polymerase chain reaction). 42.5% of the tumors studied showed LOH on at least one locus. 30% showed LOH on only one locus; 5% on two loci and 7.5% on the three loci tested. LOH occurred only on nonpapillary tumors (p = 0.03). Interestingly, all the tumors with LOH on 3p21 were >/=25 mm (p = 0.04; relative risk 1.76, confidence interval: 1.3-2.3).

[5'CpG island methylation of the suppressor gene p16/CDKN2/MTS1 in renal carcinoma]. / Metilación de las islas 5'CpG del gen supresor p16/CDKN2/MTS1 en carcinoma renal.

OBJECTIVE: To determine the methylation status of the tumor suppressor gene p16 in patients with renal carcinoma by analysis of microsatellite polymorphisms. METHODS: 40 patients with sporadic renal cancer were studied. Tumor and normal tissue from each patient were tested for methylation status of the p16 gene by analysis of microsatellite polymorphisms. RESULTS: 20% showed methylation of p16. No correlation was found between this genetic alteration and tumor features. CONCLUSIONS: Methylation of p16 was found in 20% of the patients in this series. According to the analysis, 18.5% of renal cell carcinomas showed methylation, 50% of chromophobe cell carcinomas and 25% of carcinomas of Bellini's tubules. The rest of the histological types showed no methylation.

Endothelium-independent relaxation induced by histamine in human dorsal penile artery.

1. In vitro preparations of human dorsal penile arteries were used to evaluate the effect of histamine and to characterize the histamine receptors involved in the response. 2. Cumulative administration of histamine induced a concentration-dependent relaxation in precontracted arteries. The H1 receptor agonist 2-pyridylethylamine induced a biphasic response: contraction followed by dilation. The H2 receptor agonist dimaprit produced a marked relaxation. Mepyramine, a histamine H1 receptor antagonist, led to a slight but statistically significant change in the pD2 value corresponding to the relaxant phase of the H1 receptor agonist and the histamine curve. The H2 receptor antagonist cimetidine induced a marked shift in the dimaprit concentration-response curve without affecting the maximum response. Incubation with cimetidine led to a considerable loss in the sensitivity of the arteries to histamine and in the maximum relaxation. Combined treatment with histamine H1 and H2 receptor antagonists resulted in an additional displacement compared with the effect of each antagonist alone on the histamine response. The effects observed using a histamine H3 receptor agonist and antagonist suggest that the involvement of this receptor is unlikely. 3. Removal of the endothelium was unable to reverse the histamine response. Pretreatment with NG-nitro-L-arginine methyl ester, L-arginine and indomethacin had no effect on the histamine control curve. 4. In conclusion, the vasodilation of human dorsal penile artery induced by histamine seems to be mainly mediated by muscular histamine H2 receptors, without the intervention of key intracellular mediators, such nitric oxide or relaxant prostanoids. A minor population of relaxant histamine H1 receptors cannot be excluded.

Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk.

The role of two common polymorphisms of enzymes involved in the metabolism of drugs and carcinogens was studied in relation to prostate cancer. The gene encoding one of these enzymes (NAT2) is located in an area where frequent allelic loss occurs in prostate cancer. Mutations at the genes CYP2D6 and NAT2 were analysed by allele-specific polymerase chain reaction and restriction mapping in DNA from 94 subjects with prostate cancer and 160 male healthy control subjects. Eleven prostate specimens were analysed for genotype and enzymatic activities NAT2, CYP2D6 and CYP3A by using the enzyme-specific substrates sulphamethazine and dextromethorphan. Enzyme activities with substrate specificities corresponding to NAT2, CYP2D6 and CYP3A are present in human prostate tissue, with mean +/-s.d. activities of 4.8+/-4.4 pmol min(-1) mg(-1) protein, 156+/-91 and 112+/-72 nmol min(-1) mg(-1) protein respectively. The Km values for the prostate CYP2D6 and CYP3A enzyme activities corresponded to that of liver CYP2D6 and CYP3A activities, and the CYP2D6 enzyme activity is related to the CYP2D6 genotype. The N-acetyltransferase, in contrast, had a higher Km than NAT2 and was independent of the NAT2 genotype. The CYP2D6 and CYP3A enzymes, and an N-acetyltransferase activity that is independent of the regulation of the NAT2 gene, are expressed in human prostate tissue. The presence of carcinogen-metabolizing enzymes in human prostate with a high interindividual variability may be involved in the regulation of local levels of carcinogens and mutagens and may underlie interindividual differences in cancer susceptibility.

Sustained-release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. European ALFIN Study Group.

OBJECTIVES: To assess the additive benefit of combining an alpha1-blocker and a 5alpha-reductase inhibitor. METHODS: This European, randomized, double-blind, multicenter trial involved 1.051 patients with lower urinary tract symptoms related to benign prostatic hyperplasia. Patients received sustained release (SR) alfuzosin (n = 358), a selective alpha1-blocker given at a dose of 5 mg twice daily without dose titration; finasteride (n = 344), 5 mg once daily, or both drugs (n = 349), for 6 months. Primary efficacy criteria were symptomatic improvement (International Prostate Symptom Score: I-PSS) and maximum flow rate (Qmax). Safety was assessed by monitoring adverse events. RESULTS: Symptomatic improvement was significantly higher from the 1st month of treatment with SR alfuzosin, alone or in combination; mean changes in I-PSS versus baseline at end-point were -6.3 and -6.1, respectively, compared with -5.2 with finasteride alone (SR alfuzosin vs. finasteride, p = 0.01; combination vs. finasteride, p = 0.03). The percentages of patients with a decrease in I-PSS of at least 50% were 43, 42 and 33% for SR alfuzosin, the combination and finasteride, respectively (SR alfuzosin vs. finasteride, p = 0.008; combination vs. finasteride, p = 0.009). In the overall population, increases in Qmax were greater with SR alfuzosin and the combination, compared with finasteride alone after 1 month of therapy, but changes at end-point were similar in the three treatment groups. In those 47% of patients likely to be obstructed (baseline Qmax <10 ml/s), however, mean increases in Qmax were significantly higher with SR alfuzosin, alone or in combination, whatever the visit. Finasteride, alone or in combination, significantly impaired sexual function. The incidence of postural symptoms was low and similar in the three treatment groups. CONCLUSION: In this 6-month trial, SR alfuzosin was more effective than finasteride, with no additional benefit in combining both drugs.

Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries.

1. Alteration in the flow of blood to the penis is thought to be the most frequent organic cause of erectile dysfunction or impotence. However, information concerning the penile small arteries (helicine arteries) which control blood flow between the arterial systemic circulation and the cavernous sinusoids is scarce. Therefore, the purpose of the present study was to investigate the involvement of nitric oxide, which is considered to be the main neurotransmitter in corpus cavernosum, in both the non-adrenergic non-cholinergic inhibitory neurotransmission and the endothelium-dependent responses in human penile small arteries. 2. Penile small arteries (lumen diameter 200-700 microns), which were branches of the human deep penile arteries obtained either from patients undergoing penile surgery or from organ donors, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation was performed in the presence of guanethidine and atropine to block adrenergic neurotransmission and muscarinic receptors, respectively. 3. In phenylephrine-contracted penile small arteries, electrical field stimulation (0.5-32 Hz) induced frequency-dependent relaxations of both endothelium-intact and -denuded preparations. The inhibitor of nitric oxide synthase, NG-nitro-L-arginine (3 x 10(-5) mol/l), abolished the relaxations at the lowest frequencies, while slow-developing relaxations were still observed at high frequencies (16 and 32 Hz). The inhibitory effect of NG-nitro-L-arginine was reversed in the presence of L-arginine (3 x 10(-3) mol/l). Tetrodotoxin totally abolished the relaxations to electrical field stimulation. In contracted small penile arteries in the presence of NG-nitro-L-arginine, the nitrovasodilator sodium nitroprusside induced potent relaxations. 4. The endothelium-dependnet vasodilator acetylcholine induced relaxations of penile small arteries, which were only partially reduced in the presence of NG-nitro-L-arginine. In contrast, the relaxations to acetylcholine of trabecular corpus cavernosum preparations were almost abolished in the presence of NG-nitro-L-arginine. 5. The present study suggests that relaxations of human intracavernosal small penile arteries induced by non-adrenergic non-cholinergic nerve stimulation partially involve nitric oxide and also another inhibitory transmitter causing relaxations resistant to nitric oxide synthase blockade. In addition, endothelium-dependnet relaxations in human small penile arteries are mediated by both nitric oxide and a factor resistant to NG-nitro-L-arginine.

[Primary care physicians and prostatic disease. National survey. Members of the Spanish Council of Prostatic Health]. / Los médicos de atención primaria y la patología prostática. Encuesta nacional. Miembros del Consejo Español de Salud Prostática.

The paper presents the results of a survey distributed to 15,000 primary care physicians (PCP) asking about their management of prostate conditions. From the 3.265 surveys completed, the following information was obtained. The number of visits for "prostatism" is low, 3.92 + 3.99 per week. Most PCPs inquired for symptoms related to prostate conditions regardless the initial reason for the visit. 95% refer the patient directly to the urologist, either with no further investigation or after a diagnostic evaluation or initial therapy. Vegetable extracts are the pharmacological group most commonly used by PCPs. They would accept to monitor the patient's evolution, after diagnosis and treatment by the urologist, and always with the specialist's regular supervision. Most show little sensitivity toward prostatic conditions and are aware of slight of null urological education received during their graduation. They are by a majority also ready for a retraining in urology permitting them one active participation in this pathology.

[The urologist and prostatic disease. National survey. Members of the Spanish Council of Prostatic Health]. / El urólogo y la patología prostática. Encuesta nacional. Miembros del Consejo Español de la Salud Prostática.

Analysis of the results of a survey answered by 290 urologists on their relationship with primary care physicians (PCP), as well as the diagnostic and therapeutical approach to "prostatism". According to urologists, the PCPs attitude towards these patients shows a low profile, and they lack the necessary urological training to undertake diagnosis and treatment. With regard to the urological diagnostic approach, it is surprising that 73% of urologists who work outside the hospital milieu, usually do not perform digital examination. Likewise, urography is initially requested by 47.9% of the respondents. The symptoms questionnaire are used by only part of the hospital urologist and is never used by those who have no direct relation with hospital. These tendencies are in conflict with the recommendations established by the WHO for diagnosis of the condition.

[Results of prostatectomy in the treatment of obstructive benign prostatic hypertrophy]. / Resultados de la prostatectomía en el tratamiento de la hipertrofia prostática benigna obstructiva.

Aimed to evaluate the results of surgery in patients with obstructive prostatic hypertrophy, we studied the clinical and flow measure results from 51 patients undergoing prostatectomy (31 TUR, and 20 retropubic prostatectomies). It was shown that prostatectomy significantly improved the irritation (63% of patients), and most importantly, the obstructive (89%) symptoms. Peak flow increased in 100% of patients while maximum flow percentile in 92% of patients. Post-operative results showed no correlation to the patients' age, duration of evolution or severity of urinary symptoms, weight of prostate removed or histology of the prostate. Our results were compared with those obtained with other therapeutical options, and it was demonstrated that prostatectomy (both retropubic and RUT) are, clinically and urodynamically, the most effective procedure in the treatment of obstructive prostate hypertrophy.

[High pressure filling bladder]. / Vejigas de alta presión de llenado.

A complete urodynamic study was carried out on 41 consecutive patients presenting in the cystomanometry a vesical filling pressure at maximum capacity higher than 30 cm H2O. Two groups were evident: group I with neurogenic etiology, and group II without an obvious neurogenic etiology. From its results it can be seen that a diminished vesical accommodation is not a urodynamic fact restricted to vesicourethral neurogenic dysfunction, but it happens in several non-neurogenic conditions. Within the neurogenic group, the urodynamic element most frequently associated to a diminished vesical accommodation was an inferior motor neuron-like vesicourethral dysfunction. An increased vesical filling pressure was not enough to produce urinary incontinence, being also necessary an added factor to prompt involuntary loss of urine.

[New permanent expandable prosthesis for the treatment of urethral stenosis]. / Nueva protésis autoexpandible permanente en el tratamiento de la estenosis de uretra.

The paper presents our initial experience in the treatment of urethral stenosis through implantation of a "Wallstent" self expanding resident prosthesis. A total of eleven prosthesis were placed in 10 patients with excellent results, from a clinical, urodynamic, radiological and endoscopic point of view, in 9 of them after 5 months. We believe that this kind of prosthesis can be a valid alternative to other established therapeutic options in the management of urethral stenosis. Long-term monitoring, however, will be necessary in order to corroborate the excellent results obtained in this short/medium-term observation.