Results of the spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Update after 21 years of follow-up. / Resultados de la rama española del Estudio Randomizado Europeo de Screening del Cáncer de Próstata (ERSPC). Actualización tras 21 años de seguimiento.

INTRODUCTION AND OBJECTIVE: The objective of the European Randomized Study of Screening for Prostate Cancer (ERSPC) is to assess whether prostate cancer (PCa) screening leads to an improvement of cancer-specific survival. This multicenter study (eight European countries) has recruited more than 180,000 asymptomatic men. After a follow-up period of 16 years, it has been shown that PSA screening reduces PCa mortality by 20%, and that it does not affect all-cause mortality. This article provides updated the results of the Spanish arm of the ERSPC after 21 years of follow-up. MATERIALS AND METHODS: The study invited 18,612 men (aged 45 - 70) of the Spanish section (Getafe and Parla, Madrid) to participate. They were randomly assigned to the intervention arm (serum PSA-based screening) and to the control arm (follow-up without intervention). The diagnoses of PCa were recorded, as well as the PCa-specific and all-cause mortality rates. A comparison between the survival curves of both arms of the study and detailed analysis of the causes of death were performed. RESULTS: The study finally included 4,276 men (2,415 intervention arm, 1,861 control arm). The median age, serum PSA and follow-up time were 57 years, 0.9 ng/ml and 21.1 years, respectively. There were 285 cases with PCa diagnosis, 188 (7.8%) from the intervention arm and 97 (5.2%) from the control arm (p<,001). A total of 216 (75.8%) presented organ-confined disease. There were 994 deaths were recorded; 544 (22.5%) in the intervention arm and 450 (24.2%) in the control arm. No significant differences were detected between the arms of the study in terms of cancer-specific (p=.768) or all-cause (p=.192) mortality rates. The main cause of death was malignant tumors (492 patients, 49.5% of overall mortality), and the most frequent sites were lung and bronchus (29.5%), colon and rectum (14.8%), and hematologic (9.8%). Only 20 patients (0.4% of the patients recruited) died from PCa, with no significant difference between study arms. CONCLUSIONS: In this update of the results of the Spanish section of the ERSPC study after 21 years of follow-up, we have not detected a benefit of PCa screening in terms of overall and cancer-specific survival.

[Clinical significance of prostatic intraepithelial neoplasm and atypical small acinar proliferation: relationship with prostate cancer]. / Significado clínico de la neoplasia intraepitelial prostática y de la proliferación acinar focal atípica: relación con el cáncer de próstata.

INTRODUCTION: Prostatic intraepithelial neoplasia (PIN) and atypical small acinar proliferation (ASAP) in the setting of prostatic needle biopsies are considered premalignant although questions still remain. OBJECTIVES: In this paper, we have studied the clinical relevance of these histologic findings. MATERIAL AND METHODS: We collected 138 subjects (108 PIN, 30 ASAP); in 67% we performed a second biopsy and the rate of cancer in this late biopsy were 19% and 27% respectively. We cannot identify any clinical factor to predict the finding of cancer in the re-biopsy (PSA, age, digital rectal examination, prostatic volume). RESULTS: In the follow-up, we observed higher rates of cancer for the ASAP; the finding of ASAP was the single clinical or histopathological factor that was an independent predictor of cancer. CONCLUSIONS: We observed that the finding of ASAP was an indication for re-biopsy because of the higher rates of cancer; on the contrary, the paper of PIN in the prostatic needle biopsy still requires further investigation.

[Trends in the incidence of testicular germ cell cancer in a 300.000 inhabitants Spanish population (1991-2005)]. / Tendencia en la incidencia del cáncer testicular de células germinales en un área sanitaria española de 300.000 habitantes (1991-2005).

OBJECTIVE: To describe the features and the time trends of the testicular cancer in a spanish population. MATERIALS AND METHODS: Data on incident cases of testicular germ cell cancer diagnosed in our population were extracted from the Cancer Registry of our Department. We calculed annual incidence rates of testicular cancer, the Spanish population-adjusted annual percent change (APC), age of diagnosis and the different histologic types frequencies. RESULTS: The overall incidence rate rose from 0.84 per 100,000 males to 1.91 per 100,000 males from 1991 till 2005, with a peak of 6.77 per 100,000 males in 2003. The Spanish population-adjusted APC was 2.39%. By histologic subgroup, for seminomas: the incidence rate varied from 0.84 per 100,000 males to 0.64 per 100,000 (1991-2005), with a peak of 5.41 per 100,000 in 2003 and the Spanish population-adjusted APC was 6.06. For nonseminomas, the incidence rate varied from 1.66 per 100,000 to 1.28 per 100,000 (1992-2005), with a peak of 3.65 per 100.000 in 2001 and the Spanish population-adjusted APC was 12.74. Mean ages were 31.23 years (median 30, SD 8.56) for seminomas, and 23.68 years (median 25, SD 6.85) for nonseminomas, with statistic significance (p < 0.0001). DISCUSSION: The increasing testicular cancer incidence observed for this population follows the time trends showed in other European countries.

[Smoking habit and superficial bladder tumours' natural history]. / Efecto del tabaco sobre la evolución de los tumores de vejiga.

OBJECTIVES: To disclose the features of bladder cancer in current smokers at diagnosis and to study the differences in recurrence and progression between smokers and non-smokers. PATIENTS & METHODS: 786 consecutive patients with bladder cancer from 1991 to 2004 were studied in a retrospective manner and characteristics of smokers tumours were compared to non smokers. RESULTS: 377 (48%) patients were smokers at diagnosis. There were no differences in terms of age and T stage between smokers and non smokers (t student and Chi square). We found statistical differences in tumours grade, size and multiplicity ( Chi square, p=0.046, p=0.001 and p=0.12 respectly). No differences were found between smokers and non smokers according to recurrence. (Log Rank, Breslow y Tarone-Ware N.S.). We did find differences according to progression (Log Rank p=0.03, Breslow p=0.05 y Tarone-Ware p=0.03) although it did not support multivariate study. CONCLUSIONS: Currents smokers present bigger and higher grade tumors and, more frequently in a multiple fashion at diagnosis than non-smokers.

[Urinary stress incontinence: surgical experience in our center]. / Incontinencia de esfuerzo: experiencia quirúrgica en nuestro centro.

INTRODUCTION: For the treatment of the urinary stress incontinence, there are many techniques, and today the gold standard is that described by Burch. We compared the global and each technique results about rates of postoperative continence and complications seen in our experience. MATERIALS AND METHODS: We made a retrospective analysis of 292 women that have the first surgery for urinary stress incontinence in our centre, between 1991 and 2006. We considered cure the patient who did not have any level of incontinence postoperative, we made a Kaplan-Meier analysis for the postoperative continence evaluation. Besides we studied the behaviour of the postoperative complications found. RESULTS: Mean age was 53.6 years old, and mean time of follow up was 15.6 months. The vaginal techniques were the most practised (138), followed by the TVT (57), abdominal Burch (38), vaginal wall Sling (33), and the less was the laparoscopic Burch (26). The best rates of postoperative continence after 2 years were observed in the patients treated by TVT (87.6%), then with vaginal wall Sling (84.9%), laparoscopic Burch (59.3%), abdominal Burch (59.1%), and the worst with vaginal techniques (48.2%) (p = 0.007). We found more urgency and urge incontinence in the patients treated by TVT (36.8% y 21.1% respectively), and postoperative pain with vaginal techniques (36.2%). Postoperative urine retention and postoperative high residual urine more with the vaginal wall sling (54.5%) and vaginal techniques (26.1%) respectively. CONCLUSIONS: We have the best results for the incontinence treatment in our population with the TVT technique.

[Prevalence and clinical meaning of focal and incidental prostate cancers]. / Prevalencia y significado clínico de los cánceres de próstata focales e incidentales.

OBJECTIVES: To calculate the proportion of focal and incidental prostate cancers (PCa) in our setting, to study their relationship with the findings in radical prostatectomy (RP) specimens, and to establish their clinical relevance in terms of progression and survival. MATERIAL AND METHODS: We selected patients with focal cancer, defined as a maximum extent of 3 mm in one or two adjacent prostate biopsy cores (transrectal ultrasound guided, sextant). In addition we included a group of patients with incidental T1a cancers (diagnosed after prostatectomy, nonpalpable, with less than 5% tumor in specimen). The proportion of those cancers over the total of tumors diagnosed in our health area was calculated. Also, clinical characteristics of such cancers were recorded (age, PSA, Gleason grade and score), and also therapy given. In cases that underwent RP, pathological findings were also recorded. Finally, survival analysis (Kaplan-Meier) was carried out to describe the natural history of these patients in terms of time to progression and time to death from PCa. RESULTS: From 819 patients diagnosed of PCa, 46 (5.6%) presented with focal cancer and 23 (2.8%) with stage T1a tumors. None of the patients with incidental cancer (T1a) underwent RP opposed to 17 of 46 focal T1c cancers (37%). Although none of these cases showed extracapsular extension, seminal vesicle invasion, or lymph node invasion, relevant disease (stage pT2b or higher) was found in 15 cases (88.2%) and pathological Gleason score > 7 in 2 cases (2.9%). With a mean follow-up time of 37.6 months (standard error 4.26), the probability of being free from any progression was, for T1a cancers at 2 and 5 years, of 75.4% and 57.1% respectively, and 94.4% and 94.4% respectively for T1c cases. No PCa deaths were recorded in the presented cases during the mentioned follow-up period. CONCLUSION: In our experience, the finding of microscopic or focal cancers in sextant prostate biopsy is related to a high proportion of clinically relevant tumors in RP specimens (88%). We think that expectant management of patients with such findings in prostate biopsy should be questioned.

[Natural history of metastasic prostate cancer treated with androgen deprivation therapy and secondary hormonal therapy efficiency]. / Historia natural del cáncer de próstata metastásico sometido a bloqueo hormonal y eficacia del tratamiento hormonal de segunda línea.

OBJECTIVE: to analyze metastatic prostate cancer progression in patients treated with hormonal blockade as well as second line hormonal treatments outcomes. PATIENTS AND METHODS: 199 metastatic patients were selected from a 455 hormonal treated patients pool. Time to biochemical progression was studied with Kaplan Meier analysis and patients were stratified according to pathological differentiation. Second line treatment lasting and efficacy were also assessed. RESULTS: 74 patients out of 192 metastatic patients (56.1%) progressed in terms of PSA. Median time to biochemical progression was 1.7 years (1.2-2.3, CI 95%). We did not find stadistical differences on pathological differentiation (p = 0.238). Second line treatment's efficacy, applied to 41 patients was 34.1%, without any stadistical differences among these treatments. Response treatment median time was 6.8 months without stadistical differences among different treatments (p = 0.220). CONCLUSIONS: hormonal blockade efficacy in metastatic prostate cancer has a limited value in time in our experience. One third of these patients have a limited response to a second line treatment although this response is even shorter in duration.

[The meaning of PSA progression after radical prostatectomy. Preliminary results]. / Significado de la progresión de PSA tras prostatectomía radical. Resultados preliminares.

OBJECTIVES: To report our findings regarding to the natural history of prostate cancer (PCa) that shows recurrence after radical prostatectomy (RP), in terms of time to development of metastatic disease and death from PCa. To identify independent predictors of PSA recurrence. MATERIAL AND METHODS: Retrospective analysis of 227 patients with clinically localized PCa who underwent RP. The event PSA recurrence was defined as the presence of a postoperative PSA level of 0,2 ng/ml or higher at least 3 months after surgery. Hence, cases with shorter follow-up time were excluded from analysis. No adjuvant therapy (radiotherapy or hormonal therapy) was performed in the included population. Recurrence free survival was calculated during the follow-up period (Kaplan-Meier analysis). Uni and multivariate study was performed in order to assess the ability of factors as preoperative PSA level, Gleason score in surgical specimen, capsular penetration, positive surgical margins (excluding urethral), extracapsular extension, positive pelvic lymph nodes, and seminal vesicle invasion, to predict PSA recurrence. Finally, we selected the group of patients with PSA recurrence and calculated the probability of being free from distant metastatic disease during the follow-up period. Also, function of disease-specific survival was calculated. RESULTS: A total of 208 records were finally included in the study. Median age was 61 years. A total of 47 (22.6%) presented with extracapsular extension. Median follow-up time was 35.8 months, and 49 (23.6%) developed PSA recurrence. Recurrence free survival was 79.9% and 67.4% at 2 and 5 years, respectively. Only three factors were identified with the aid of multivariate analysis as independent predictors of recurrence: preoperative PSA >= 10 ng/ml (hazard ratio--HR--3.03), Gleason score in surgical specimen 8 or higher (HR 3.42), and the finding of capsular penetration (HR 2.17). When only patients with PSA recurrence were considered, 16.3% developed distant metastasis. Probabilities of being free from distant disease after PSA recurrence were 97.7% and 86.9% at 2 and 5 years respectively (actuarial median time 110.8 months). Only 2 patients died from PCa, therefore disease-specific mortality analysis was not performed. CONCLUSIONS: Although an important proportion of patients present with PSA recurrence after RP in our setting, the prognosis in term of development of metastatic disease is acceptable in the short-medium term. Anyway, further analysis will be needed to ascertain the evolution of these patients in the long term.

[Effect of polyphenols from the Mediterranean diet on proliferation and mediators of in vitro invasiveness of the MB-49 murine bladder cancer cell line]. / Efecto de polifenoles de la dieta mediterránea sobre la proliferación y mediadores de la invasividad "in vitro" de la linea de cancer vesical murino MB-49.

OBJECTIVE: To evaluate the effect of different polyphenols on the proliferation and invasive capacity of MB-49 murine bladder tumor cell lines and to identify the mediators involved in this process. MATERIALS AND METHODS: MB-49 murine bladder cancer cells were cultured in media supplemented with resveratrol, rutin, morin, quercetin, gallic acid and tannic acid (all of them are polyphenols usually present in Mediterranean diet) for periods of 24, 48 and 72 hours to quantify the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in the culture medium, as well as of metalloproteinase-9 (MMP-9) and cell proliferation. RESULTS: All the polyphenols studied significantly inhibited proliferation of MB-49 cells, varying according to the time periods and doses used. The cells in the media supplemented with the nutrients to study did not show inhibition of mRNA expression of urokinase-type plasminogen activator (uPA) or its high affinity receptor (uPAR). It was even slightly increased in certain cases. However, mRNA expression of metalloproteinase-9 was strongly inhibited. CONCLUSIONS: The polyphenols present in our usual diet exert an effect on the proliferation and mediators of bladder tumor invasiveness in MB-49 cells.

[Left inferior vena cava with renal cell carcinoma]. / Vena cava renal izquierda en un paciente con carcinoma de células renales.

We presented a case of inferior vena cava on the left side diagnosed by abdominal CT scan during the study of a renal cell carcinoma in the right side. This anomaly is very rare but it may suppose a more difficult approach to the nephrectomy.

[Acute urinary retention and hematuria secondary to metastatic renal clear-cell carcinoma to the penis]. / Retención urinaria aguda y hematuria secundarias a metástasis peneanas por carcinoma renal de células claras.

Renal cell carcinoma have a great capacity of dissemination and have a great variety of clinical presentation. We exposed a clinical note of a patient diagnosed of renal cell carcinoma who developed hematuria and acute urinary retention due to a penis metastasis. Next we review the literature about this topic.

[Diet and prostate cancer]. / Dieta y cáncer de próstata.

Prostate cancer is the first neoplasia in the United States accounting the second in cancer deaths. With all the treatments strategies in debate because of their side effects, is very important try to elucidate prevention mechanisms that may be implicate in the development of this disease, between these, nutrients have been of mayor importance. In the present review we tried to study the most important nutritional factors implicated in the development and prevention of prostate carcinoma. We focus our attention over the polyphenols of the red wine, which influence over cellular proliferation and apoptosis in LNCaP cells have been studied in our Department.

[Effect of sacral roots block in the prostatic structure of the rat]. / Efecto del bloqueo de raíces sacras en la estructura prostática de la rata.

OBJECTIVE: To validate a simplified model of neural manipulation of the lower urinary tract of the rat, by means of alcoholic blockade of sacral roots. MATERIAL AND METHODS: Twenty Sprague-Dawle rats (aged 3 months) underwent alcohol sacral root blockade under total anesthesia with previous needle placement monitoring (electrostimulation). After 28-30 days, ipsilateral ventral prostatic lobe (VL) was obtained. Macroscopic and light microscopy (LM) studies were performed (computerized image analysis). Results were compared with 20 LV from non manipulated rats. RESULTS: A slight non significant decrease of LV weight in the blockade group was notice. LM study showed a reduced epithelial height after manipulation. Gland compartment mean proportions were: control group: 28.1% (epithelial), 29.8% (stromal), y 70.2% (glandular -lumen plus epithelium-); study group: 30.5% (not significant), 37.4% y 62.3% (both p < 0.05) respectively. Epithelium area did not suffer any variation. A reduced vascular overall count was noted in the study group. Ipsilateral diffusion of blockade solution was shown in 9 rats (45%), and bilateral in 11 (55%). CONCLUSIONS: Alcoholic sacral root blockade produces an atrophy of the glandular component (due to luminal shrinkage, without epithelial change). No differences were found after the macroscopic study. This study could not reproduce the changes produced after standard surgical denervation, therefore we cannot recommend this method to be used in future models.

[Non-surgical treatment of testicular cancer: guidelines for the urologist]. / Aspectos no quirúrgicos del cáncer testicular: guía práctica para el urólogo.

Near 70% of patients diagnosed with testicular seminoma make their presentation without metastasis. Although spread at the time of diagnosis is the rule, 25% of non-seminomatous germ-cell tumours are found confined to the testicle at presentation. Standardization of diagnostic and follow-up methods -within reach of most urology services- should allow a closer relationship between urologists and testicular tumours. Observation of "aggressive" surveillance schedules for stage I non-seminomatosous tumours confined with no risk factors, and use of radiotherapy to treat low degree (I,IIa and IIb) seminomas should allow urologists an initial control of up to 50% of patients. Occurrence of relapse or presentation in advanced stages force the use of chemotherapy. The present paper outlines the most basic aspects of non-surgical treatment of patients with testicular tumours.

[Relationship between a benign fibroepithelial polyp and a pelvic nephroblastoma: report of a case]. / Relación entre un pólipo fibroepitelial benigno y un nefroblastoma piélico: a propósito de un caso.

The purpose of this paper is to report one case of left pyelic Wilms' tumour in a 17-year old male patient. Pre-operative diagnosis was complicated by a background of prior surgery on the same kidney due to a benign fibroepithelial polyp. The possible concomitences are analyzed while the relevance of an extensive pathoanatomical study to avoid possible diagnostic errors is emphasized.

[Ultrastructural morphometric study of the prostate of the rat after microsurgical denervation]. / Estudio morfométrico ultraestructural de la próstata de la rata tras la denervación microquirúrgica.

OBJECTIVE: To analyze the effects of rat prostate denervation on the ultrastructure of this gland. MATERIAL AND METHODS: Eighty Sprague-Dawley rats (300-350 g. weight) were studied. Forty-two were anesthetized and right major pelvic ganglion (MPG) excised. After 28-30 days, same size prostatic ventral lobe (VL) was obtained for transmission electron microscopy (TEM) study and computerized image analysis. These results were compared with those from 38 right VLs of same aged, non-operated rats. RESULTS: A significant decrease of supranuclear and cell heights was observed as well as of the area of epithelial cells after denervation (change in cell polarity). A reduction of Golgi apparatus and endoplasmic reticulum areas, and of secretory granules and apical microvilli count (p < 0.001) was also demonstrated in the denervated rats. These findings are consistent with a change of these cells towards a less active phenotype. Stromal smooth muscle cells, on the other hand, showed only an increase of cytoplasmic ribosomal aggregates area. CONCLUSIONS: The present study showed an epithelial atrophy of rat prostate after denervation. Ultrastructural findings also suggest an overall decrease of epithelial cell's secretory activity. Nevertheless, the increase of ribosomal area in stromal smooth muscle cells could reflect their activation after denervation.

[Initial aspects of a program for in vitro transfection of cytokine genes into LNCap tumor cells]. / Aspectos iniciales de un programa para la transfección in vitro de genes de citokinas a células tumorales LNCaP.

OBJECTIVES: To characterize the conditions and kinetics for in vitro growth of tumoral cells LNCaP. METHODS: Determination of proliferation curves and time to cell duplication through spectrophotometry and manual cell counts in haemocytometer with and without foetal calf serum (FCS) challenge. RESULTS: Data from the spectrophotometry and manual cell counts were correlated by mean of the equation through the number of cells = absorbance at 595 nm x 227,530-14,160. The correlation coefficient r was 0.99. Cell proliferation was higher in the presence of FCS (p > 0.001), the final culture density being 5.4 times higher than the baseline. Similarly, time to duplication in the presence of FCS was 36.4 hours. CONCLUSIONS: This experiment allowed to establish the local conditions for growth of LNCaP cells. In contrast to the behaviour exhibited by other malignant cells in culture, LNCaP cells grow slowly and require the stimulus provided by FCS. Both aspect are of the highest significance when adopting the pre-established timetables and logistic to the actual laboratory operation.

[Differential traits of prostatic cancer detected through an early screening program versus the one detected during urologic consultation]. / Rasgos diferenciales del cáncer de próstata procedente de un programa de detección precoz frente al detectado en una consulta de urología.

OBJECTIVE: To compare some features of prostate cancers (PCa) detected in a screening program, versus cancers diagnosed in an outpatient clinic. MATERIAL AND METHODS: Retrospective study of 393 patients with biopsy evidence of PCa: 93 (23.7%) from a screening campaign, and 300 (76.3%) detected in an outpatient Urology clinic. Features studied at the moment of diagnosis were age, PSA, digital rectal examination (DRE), transrectal ultrasound (TRUS) characteristics and volume stimation, PSA density (PSAD), clinical stage and Gleason score. A comparison was established between the two groups of patients taking into account the mentioned parameters. RESULTS: A higher age, PSA and DPSA values were found among cancers detected out of the screening program. A greater probability of abnormal DRE and a more advanced clinical stage was also noted. In the screening group, 78.5% of the cancers were localized and 8.6% metastatic. In the outpatient clinic group, the proportions were 50.7% and 26%, respectively. No differences were found with respect to TRUS findings, prostate volume, or Gleason score. CONCLUSIONS: Cancers detected in screening programs are found in earlier stages. Nevertheless, results from long term randomized studies are necessary to verify if these data really mean that a disease-specific mortality reduction can be achieved.

[Conditions for the development of a program of reverse transcriptase-polymerase chain reaction for molecular staging of prostatic cancer]. / Condiciones de desarrollo de un programa de reacción en cadena de la polimerasa-transcriptasa reversa para el estadiaje molecular del cáncer de próstata.

OBJECTIVE: To determine accurately the conditions for the development of tests using RT-PCR for PSA in patients with prostate cancer. METHOD: Gen amplification of PSA in cultures of the human prostate tumoral cell line LNCaP with RT-PCR under hot-start conditions, and verification through enzyme restriction digestion of the PCR product. Also, calculation of the PCR test limit of detection through serial dilutions of LNCaP cells in peripheral blood mononucleate cells. RESULTS: A highly specific, easy to perform, reproducible RT-PCR protocol has been developed. The lowest limit of detection reached was 1 PSA synthesising cell per 10(6) peripheral blood mononucleate cells. CONCLUSIONS: RT-PCR is a highly sensitive technique that allows detection of small numbers of PSA producing cells in peripheral blood. This experience allows to establish with precision the conditions for the development of RT-PCR tests for PSA.

[Effect of cell differentiation in prostatic cancer on basal PSA]. / Influencia de la diferenciación celular del cáncer de próstata sobre el PSA basal.

The effect of cell differentiation on PSA production in patients with prostate cancer has been evaluated. With this intention 70 patients were included and were analyzed for age, T stage, cell differentiation, bone scan involvement and PSA level prior to therapy. In well-differentiated tumours mcan PSA was 31.3 ng/mL, 56.6 in those with moderate differentiation and 31.6 in poorly differentiated ones (p > 0.05). Multivariate analysis shows no significant differences between both variables, but and inverse relationship between cell differentiation and PSA production (r = -0.27, p > 0.05) can be seen. The most influential variable on PSA levels was de extent of bone scan involvement. Cell differentiation as confusion variable to interpret PSA values in poorly differentiated tumours deserves further study to know the exact role of this protein as a treatment response criterion in prostate cancer.