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Alexandre R Zlotta

Publications and source records attributed to Alexandre R Zlotta.

At least 19 recordsLinked to original sources

How do I treat and follow my TUNA patients.

Transurethral needle ablation (TUNA) of the prostate is an alternative treatment for benign prostatic hyperplasia (BPH) generating temperatures around 100 degrees C leading to necrotic lesions inside the prostate. TUNA is a minimally invasive, low morbidity associated, approach that uses radiofrequency energy. The needles are covered by teflon shields that protect the urethra from thermal injury. Since the introduction of TUNA, there has been a constant upgrading of the device to improve treatment quality. The main advantage of this therapy is the possibility of an outpatient care due to its anaesthesia-free option with a prostatic block. Catheterisation after the procedure is required in 10-40% of cases. Long-term data (5 years) on TUNA demonstrate a sustained improvement of both IPSS score and urinary flow. About a quarter of patients require further intervention at 5 years' follow-up. The safety profile, along with the significant improvement in both objective and subjective parameters observed after TUNA, makes it an attractive approach for symptomatic BPH.

Humans↗

Pharmacotherapy for prostate cancer, with emphasis on hormonal treatments.

For more than half a century, hormonal therapy has been one of the cornerstones of prostate cancer therapy. However, the position and timing of androgen deprivation therapy is continuously challenged. Nowadays, it is often combined with other types of treatment in a multi-modal approach, especially with radiation therapy. Besides the well-known luteinising hormone-releasing hormone agonists, several developments have been introduced (e.g., luteinising hormone-releasing hormone antagonists or improved depot formulations achieving a better pharmacokinetic slope and lower testosterone levels). Research developments include a better understanding of the different gonadotropin-releasing hormone isoforms, the ligand-independent transformation of the androgen receptor and androgen receptor overexpression in hormone-insensitive disease. Prostate cancer, previously thought to be chemotherapy insensitive, is now treated at the metastatic stage by taxane-based chemotherapies. The combination of hormonal therapy and chemotherapy is currently studied at various stages of the disease, as early as localised or locally advanced prostate cancer. It is very likely that, in the future, pharmacological treatment for prostate cancer will include combination therapies rather than monotherapies. The authors suggest an in-depth re-evaluation of the place of androgen deprivation therapy in prostate cancer.

Animals↗

Evaluation of male sexual function in patients with Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon), Tamsulosin or Finasteride.

OBJECTIVES: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. METHODS: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. RESULTS: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (-0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline (r2 = 0.032). Although there was a correlation between the MSF-4 and age at baseline (r2 = 0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. CONCLUSION: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

Adrenergic alpha-Antagonists↗

The role of luteinizing hormone-releasing hormone therapy in locally advanced prostate cancer and biochemical failure: considerations for optimal use.

BACKGROUND: More patients are being diagnosed with prostate cancer at an earlier age with earlier stage disease because of advances in screening and detection. Investigators continue to explore the use of hormone therapy, particularly luteinizing hormone-releasing hormone (LHRH) analogues, earlier in the course of disease. OBJECTIVE: This review summarizes clinical evidence regarding the safety and efficacy of LHRH analogues in the treatment of locoregional disease or following biochemical failure. METHODS: Relevant information from clinical studies was identified through a MEDLINE search of the medical literature published in English in the last 5 years (search terms: LHRH and prostate cancer). The search included prospective and retrospective clinical studies on LHRH therapy in locally advanced prostate cancer. Additional relevant publications published before 1999 were identified from citations in the resulting articles. RESULTS: The available clinical evidence suggests that the use of LHRH analogues as adjuvant or neoadjuvant therapy in conjunction with radiation therapy may improve survival outcomes. Few studies have evaluated the use of LHRH analogues after biochemical failure. However, several related studies indicate that initiating hormone therapy earlier rather than later may provide some clinical benefit. When considering early initiation of LHRH therapy, the potential risks of long-term treatment must be considered. Physiologic changes, such as deterioration of body composition and bone quality, may have important effects on the risk of developing cardiovascular disease and osteoporosis. CONCLUSIONS: Although some clinical evidence supports the use of LHRH analogues as adjuvant or neoadjuvant therapy or following biochemical failure, further study is needed. In the meantime, clinicians should carefully weigh the potential benefits and risks of early hormone therapy when making treatment decisions.

Chemotherapy, Adjuvant↗

Is seminal vesicle ablation mandatory for all patients undergoing radical prostatectomy? A multivariate analysis on 1283 patients.

OBJECTIVE: With a shift in prostate cancer stage and a majority of patients operated nowadays with PSA levels <10 ng/ml, rates of seminal vesicle (SV) invasion found on radical prostatectomy specimens have decreased as compared to historical data. Since SV-sparing surgery may possibly have an influence on post-operative erectile dysfunction and urinary recovery, we tried to determine which patients could be safely spared SV excision during radical prostatectomy. MATERIAL AND METHODS: We used preoperative data from 1283 patients operated by radical retropubic prostatectomy--777 with serum PSA <10.0 ng/ml--to predict SV invasion on final pathological examination. Variables analyzed included age, digital rectal examination, serum PSA, biopsy Gleason score and percentage of biopsy cores invaded by prostate cancer. Statistical analysis included univariate, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves. RESULTS: Out of 1283 patients, 137 (10.6%) had SV involvement, 41/777 (5.2%) with PSA <10.0 ng/ml, 16.1% in the 10-20 ng/ml range and 26.2% when PSA was >20 ng/ml. Percentage of biopsies affected by prostate cancer and biopsy Gleason score were significant predictors of SV invasion in multivariate analysis, both in the entire population and in the subset of patients with PSA <10.0 ng/ml (p < 0.0001). Probability graphs created for patients with PSA <10 ng/ml indicate a risk of seminal invasion <5% when Gleason score on biopsy is <7 or when the percentage of biopsies affected by cancer is <50%. CONCLUSIONS: Resection of SV might not be "oncologically" necessary in all patients undergoing RP when PSA levels are below 10 ng/ml except when biopsy Gleason score is > or =7 or when more than 50% of prostate biopsy cores show cancer involvement. SV-sparing surgery could be prospectively compared to standard retropubic prostatectomy in selected individuals analyzing potential benefits on erectile function and urinary continence.

Aged↗

Radical prostatectomy: a prospective comparison of oncological and functional results between open and laparoscopic approaches.

We prospectively compared, within the same center and during the same period of time, the perioperative parameters as well as the oncological and functional results of both open retropubic (ORP) and laparoscopic radical prostatectomy (LRP). From September 1999 to September 2001, 162 patients with prostate cancer were treated with radical prostatectomy, 77 using an open retropubic technique, and 85 by the laparoscopic extraperitoneal approach. We prospectively recorded pre-, per- and postoperative parameters and complications, and evaluated the carcinological and functional results, comparing both approaches. There were no significant differences in the preoperative characteristics of the two groups. Mean operative time was statistically longer with LRP than with ORP (288 vs 168 min, P<0.0001) but median blood loss was decreased (400 vs 1,300 ml, P<0.0001). Major complications occurred in a similar number of cases (5% vs 2.4%, NS) while minor complications occurred more frequently with ORP (24.6 vs 11.8%, P=0.003). Pathological examination revealed a similar distribution of Gleason scores and stages in each group. Positive surgical margins in pT2 cases occurred in 7.8% of LRP and 7.3% of ORP. Continence rates (no pad and no leakage at all) were similar (83.9% in ORP vs 80.7% in LRP, NS). Potency rates were similar after 1 year in patients undergoing bilateral nerve sparing (55% in ORP vs 65% in LRP, NS). However, patients operated by LRP had more spontaneous erections. We conclude that this prospective, comparative study shows that LRP, when performed in specialized centers, gives oncological and functional results comparable to open surgery.

Aged↗

Prevention of prostate cancer.

Prostate cancer is an ideal candidate for chemoprevention because of its high prevalence, long latency time, hormone dependency, precursor lesions, and its unique serum marker, PSA. Chemoprevention is the administration of drugs or other agents which aim to prevent the induction or inhibit/delay cancer progression. Large-scale studies favor environmental rather than genetic factors as key determinants of prostate cancer development. Among these environmental factors, nutrition certainly has a leading role. Numerous basic science studies but also clinical studies indicate that dietary compounds or diet modifications may ultimately play a major role in prostate cancer promotion and inhibition. Definitive proofs are often difficult because of methodological problems and complex triggering cascades. New pharmaceutical drugs with minimal toxicity are also currently evaluated.

Antineoplastic Agents↗

Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers.

OBJECTIVE: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. METHODS: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. RESULTS: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s (p<0.01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p<0.001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. CONCLUSIONS: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run.

Aged↗

An artificial neural network for prostate cancer staging when serum prostate specific antigen is 10 ng./ml. or less.

PURPOSE: An artificial neural network was developed to improve the prediction of pathological stage before radical prostatectomy based on variables available at biopsy and clinical parameters. MATERIALS AND METHODS: We used the prospectively accrued European prostate cancer detection data base to train an artificial neural network to predict pathological stage in 200 men with serum prostate specific antigen (PSA) 10 ng./ml. or less who underwent radical prostatectomy. Variables included in the artificial neural network were patient age, serum PSA, free-to-total PSA ratio, PSA velocity, transrectal ultrasound calculated total and transition zone volumes with their associated PSA parameters (transition zone PSA density and PSA density), digital rectal examination and Gleason score on biopsy. Two multilayer perceptron neural networks were trained on the remaining variables. Data on the 200 patients were divided randomly into a training set, a test set and a validation or prospective set. RESULTS: Overall classification accuracy of the artificial neural network was 92.7% and 84.2% for organ confined and advanced prostate cancer staging, respectively. For preoperatively predicting local versus advanced stage the area under the ROC curve for the artificial neural network was significantly larger (0.91) compared with logistic regression analysis (0.83), Gleason score (0.69), PSA density (0.68), prostate transition zone volume (0.63) and serum PSA (0.62) (all p <0.01). CONCLUSIONS: The artificial neural network outperformed logistic regression analysis and correctly predicted pathological stage in more than 90% of the validation patients with serum PSA 10 ng./ml. or less based on clinical, biochemical and biopsy data. In the future artificial neural networks may represent a significant step for improved staging of prostate cancer when counseling patients referred for radical prostatectomy or other curative treatments.

Adult↗

The need to embrace molecular profiling of tumor cells in prostate and bladder cancer.

PURPOSE: Current treatment strategies for urological cancer are still based on empirical formulae as opposed to treatment tailored for each cancer patient. To individualize treatment, the multiple molecular abnormalities within tumor cell populations needs to be mapped out. The aim of this article is to explain molecular profiling (MP) and its associated techniques so that the process is not purely seen as a research tool but as a future adjunctive measure in patient diagnosis and treatment. EXPERIMENTAL DESIGN: A Medline search of publications relating to MP of prostate and bladder cancer was carried out. A review article was written combining the relevant published literature along with the clinical and scientific experience of both centers. RESULTS: The advent of MP now provides a strategy by which these molecular abnormalities can be assessed. As well as being of diagnostic and prognostic use, these molecular profiles will identify putative molecular abnormalities within tumor cells that may be appropriate for therapeutic modulation. CONCLUSIONS: In prostate and bladder cancer, mapping out the molecular abnormalities could be translated into a valuable tool to help solve difficult issues regarding patient management decisions.

Gene Expression Regulation, Neoplastic↗

Comparison of laparoscopic radical prostatectomy techniques.

Over the past years, laparoscopic radical prostatectomy has emerged as an attractive, exciting, and new approach for the surgical treatment of localized prostate cancer. Several centers in Europe and the United States have developed their own technique and have already published their first results. Two main routes have been used, namely, the transperitoneal and extraperitoneal approaches. Data from the literature and available experience demonstrate that this laparoscopic procedure is feasible and teachable and that oncologic and functional results seem comparable to those of classic open radical prostatectomy. Minimal bleeding, reduced blood transfusion rates, shorter hospitalization, and shorter recovery time are unquestionable advantages for laparoscopic procedures. Laparoscopic radical prostatectomy remains a difficult intervention and should be performed in selected centers with experienced teams who already have extensive laparoscopic experience and who recruit enough patients to grant them the proper amount of expertise. This is the only way to achieve excellence in terms of oncologic and functional results.

Humans↗

Complexed prostate-specific antigen, complexed prostate-specific antigen density of total and transition zone, complexed/total prostate-specific antigen ratio, free-to-total prostate-specific antigen ratio, density of total and transition zone prostate-specific antigen: results of the prospective multicenter European trial.

This prospective, multicenter European Prostate Cancer Detection study evaluated the value and performance of the molecular forms of prostate-specific antigen (PSA) and their derivatives in combination with prostate gland and transition zone volumes in early detection of prostate cancer in patients with PSA levels between 4 and 10 ng/mL. Of 750 men enrolled at 7 different European urology centers into the study between November 2001 and March 2002, 340 (45.3%) had a total PSA (tPSA) between 4 and 10 ng/mL (age range, 46 to 87 years). In all patients, the ratio of complexed PSA (cPSA) to tPSA (c/tPSA), cPSA density (cPSAD), cPSAD of the transition zone, PSA, free PSA (fPSA), ratio of fPSA to tPSA (f/tPSA), tPSA density (PSAD), and PSAD of the transition zone were measured and collected 5 to 10 minutes before the sextant biopsy with 2 additional transition zone cores. Measurements of tPSA and fPSA were done with the AxSYM test, whereas cPSA was measured with the ACS 180 cPSA assay. All patients had a transrectal ultrasound-guided sextant prostate biopsy, and 2 additional transition zone biopsies and total and transition zone volumes were measured at the time of biopsy. Histopathologic findings revealed benign histology in 237 patients and prostate cancer in 103 patients (69.7% and 30.3%, respectively). Statistically significant differences included larger total volumes, larger transition zone volumes, and f/tPSA in patients with benign disease (P = 0.0009, P <0.0001, P <0.0001, respectively). At 90% and 95% sensitivity, specificity of cPSA was significantly greater than that for PSA (P <0.0001). At sensitivity levels of 90% and 95%, the specificity of the cPSA assay using cutoff values of 3.06 and 2.52 ng/mL was 20.3% and 9.1%, respectively. A cPSA cutoff value of 6.95 ng/mL and 7.57 ng/mL afforded 90% and 95% specificity for detecting prostate cancer. The area under the curve (AUC) in the receiver operating characteristics curve of cPSA was statistically significantly higher compared with tPSA (60.8 vs 56.9, P = 0.032). AUC for volume-related parameters PSAD, cPSAD, PSAD of the transition zone, and cPSAD of the transition zone were 62.8%, 63.1%, 63.0%, and 63.6%, respectively. cPSA performs better than tPSA in the differentiation between benign disease and prostate cancer and provides similar information to the f/tPSA ratio. In addition, cPSA and cPSA volume-related parameters (cPSAD, cPSAD of the transition zone) further improved the specificity of PSA in early detection of prostate cancer.

Aged↗

Computerised assessment of maximum urinary flow: an efficient, consistent and valid approach.

OBJECTIVES: To evaluate the relative accuracy of a computerised method to quantitatively assess maximum urinary flow. METHODS: A total of 1147 uroflows were evaluated by the computerised method and by three experts from different European countries. The sample consisted of uroflows from the respective visits by a 20% sample of randomly chosen patients (n = 223) with lower urinary tract symptoms with participation in two clinical trials in which the efficacy and safety of Permixon was evaluated. The proportions of automated maximum flow values included in the 10% extended range of experts (and their 95% confidence intervals) were assessed, as well as the concordance coefficients between experts and the computerised method and the paired Student's t-test for the average differences between experts and computer. RESULTS: The rate of agreement between experts and computer varied between about 95 and 100% over factor levels for visit, type of machine and country. Concordance coefficients indicated good agreement between experts and the automated method. When looking at average differences between experts and the computer, the smallest differences were observed between experts 2, 3 and the computer (differences not statistically significant). Statistically significant average differences were observed between expert 1 and the other experts as well as between expert 1 and the computer. CONCLUSIONS: The computerised assessment decreases the fraction of variability of maximum urinary flow caused by artifacts as well as intra- and inter-expert variation. The computerised assessment of maximum urinary flow is an efficient, consistent and valid approach to quantitatively assess maximum urinary flow in clinical trials.

Decision Making, Computer-Assisted↗

Repeat prostate biopsy: who, how and when?. a review.

Urologists are frequently faced with the dilemma of treating a patient with a high index of suspicion of prostate cancer (PCa), but an initial set of negative biopsies. In this review, we evaluated the current knowledge on repeat prostate biopsies, focusing on when to perform them and in which patients, how many samples to take, where to direct the biopsies and what morbidity should be expected. We focussed on the available literature and the multicenter European Prostate Cancer Detection (EPCD) study. The EPCD study included 1051 men with a total PSA from 4 to 10 ng/ml who underwent a transrectal ultrasound (TRUS) guided sextant biopsy and a repeat biopsy in case of a negative initial biopsy. Most studies support that increasing the number of biopsy cores as compared to the sextant technique and improving prostate peripheral zone (PZ) sampling result in a significant improvement in the detection of prostate cancer without increase in morbidity or effects on quality of life. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. At least 10% of patients with negative sextant prostatic biopsy results in the EPCD study were diagnosed with PCa on repeat biopsy, percent free PSA and PSA density of the transition zone being the most accurate predictors. Despite differences in location (more apico-dorsal) and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy were similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Indications and ideal number of biopsy cores to take when repeating biopsies in patients who already underwent extensive biopsy protocols on the first biopsy remains to be determined.

Biopsy↗