Geometrical modified nesbit corporoplasty to correct different types of penile curvature: description of the surgical procedure based on geometrical principles and long-term results.

We present the use of a modified corporoplasty, based on geometrical principles, to determine the exact site for the incision in the tunica or plaque and the exact amount of albuginea for overlaying to correct with extreme precision the different types of congenital or acquired penile curvature due to Peyronie's disease. To describe our experience with a new surgical procedure for the enhancement of penile curvature avoiding any overcorrection or undercorrection. Between March 2004 and April 2013, a total of 74 patients underwent the geometrical modified corporoplasty. All patients had congenital curvature until 90° or acquired stable penile curvature 'less' than 60°, that made sexual intercourse very difficult or impossible, normal erectile function, absence of hourglass or hinge effect. Preoperative testing included a physical examination, 3 photographs (frontal, dorsal and lateral) of penis during erection, a 10 mcg PGE1-induced erection and Doppler ultrasound, administration of the International Index of Erectile Function (IIEF-15) questionnaire. A follow-up with postoperative evaluation at 12 weeks, 12 and 24 months, included the same preoperative testing. Satisfaction rates were better assessed with the use of validated questionnaire such as the International Erectile Dysfunction Inventory of the Treatment Satisfaction (EDITS). Statistical analysis with Student's t-test was performed using commercially available, personal computer software. A total of 25 patients had congenital penile curvature with a mean deviation of 46.8° (range 40-90), another 49 patients had Peyronie's disease with a mean deviation of 58.4 (range 45-60). No major complications were reported. Postoperative correction of the curvature was achieved in all patients (100%). Neither undercorrection nor overcorrection were recorded. No significant relapse (curvature>15°) occurred in our patients. Shortening of the penis was reported by 74% but did not influence the high overall satisfaction of 92% (patients completely satisfied with their sexual life). The erectile function was analyzed in both groups, Student's t-test showed a significant improvement in erectile function, preoperative average IIEF-15 scores were 17.43±4.67, whereas postoperatively it was 22.57±4.83 (P=0.001). This geometrical modified Nesbit corporoplasty is a valid therapy which allows penile straightening. The geometric principles make the technique reproducible in multicentre studies.

[Limitations on the interpretation of prostate-specific antigen serum levels]. / Limiti nell'interpretazione dei livelli sierici dell'antigene specifico prostatico (PSA).

Recent data suggest that PSA expression can be directly influenced by some factors, independently from the variation in prostate cell growth. Some growth factors such as fibroblast growth factor, transforming growth factor beta and epidermal growth factor, seem to be directly involved in the regulation of mRNA-PSA expression, whereas androgens could have an indirect activity. On the basis of these experimental data, this review tries to analyze some limits of PSA and some recent data on the role of PSA-isoforms, in particular in the follow-up of prostate cancer patients submitted to radical prostatectomy or hormone-therapy. Moreover, relevant informations can be obtained analyzing the variance of PSA in patients submitted to intermittent androgen deprivation.

Penile metastasis from carcinoma of the prostate in a patient with high serum prostate specific antigen levels.

Prostatic carcinoma metastasizing to the penis is rare. Prognosis is poor with survival ranging from 1 to 24 months. A patient with prostate cancer and a serum Prostate Specific Antigen (PSA) level over 200 ng/ml, submitted to radical retropubic prostatectomy (RRP) and after 2 months presenting with two painful nodules in the penis, is described.

New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.

Three new different aspects of prostate cancer have been considered in this review: the existence of an hereditary form, the role of estrogens as predisposing factors and the efficacy of differentiation therapies. Prostate cancer shows a stronger familial aggregation than colon and breast carcinoma. Hereditary prostate cancer is distinguished by early age at onset and autosomal dominant inheritance within families. However, only 2% of all prostate cancer in United States white men occur in those 55 years old or younger. Thus, the impact of hereditary prostate cancer in the population is the greatest at younger ages but this accounts for only a small proportion of the total disease burden. Using the developmentally estrogenized mouse model, an alternative role for estrogens as a predisposing factor for prostate diseases was proposed: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to neoplasia. A combination therapy employing both differentiation therapy and hormone therapy may be effective in the treatment of advanced prostate cancers. Recent advances in the field of differentiation therapy have resulted in the development of novel retinoic acid metabolism blocking agents. Unlike previous differentiating agents such as the retinoids, these agents increase the endogenous levels of retinoic acid by inhibiting its breakdown in cancer cells.

Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia.

BACKGROUND: The n-hexane lipido-sterol extract of Serenoa repens (LSESr, Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic agent used in the treatment of benign prostatic hyperplasia (BPH), has a multisite mechanism of action including inhibition of types 1 and 2 5alpha-reductase and competitive binding to androgen receptors in prostatic cells. Here, the response of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed. METHODS: BPH samples were sectioned in periurethral, subcapsular, and intermediate regions: in each region T, DHT, and EGF were determined by radioimmunoassay after purification on celite columns or Sep-pak C18 cartridges. RESULTS: In the untreated group, T, DHT, and EGF presented the highest concentrations in the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/- 551 pg/g tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g tissue, and 10.8 +/- 1.4 ng/g tissue, respectively). In the LSESr-treated group, a statistically significant reduction was observed, mainly in the periurethral region of DHT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF (6.98 +/- 2.48 ng/g tissue, P < 0.01), with increased T values (1,023 +/- 101 pg/g tissue, P < 0.001). CONCLUSIONS: The decrease of DHT and the rise of T in BPH tissue of patients treated with Permixon confirms the capacity of this drug to inhibit in vivo 5alpha-reductase in human pathological prostate. A marked decrease of EGF, associated with DHT reduction, was also observed. These biochemical effects, similar to those obtained with finasteride, are particularly evident in the periurethral region, whose enlargement is responsible for urinary obstruction, with respect to the subcapsular region. A possible speculation is that the preferential reduction of DHT and EGF content in the periurethral region is involved in the clinical improvement of the obstructive symptoms in BPH during LSESr therapy.

[The role of prostate specific antigen and its derivatives (age-specific PSA, PSA density, velocity, free/total PSA) in the diagnosis of prostate cancer]. / Ruolo dell'antigene prostatico specifico e dei suoi indici derivati (PSA età-specifico, densità-PSAD, velocità-PSAV, PSA libero-f-PSA) nella diagnosi del carcinoma della prostata.

PSA is the most useful tumor marker for the diagnosis and treatment of prostate cancer. Its clinical use, however, still lacks the necessary sensitivity and specificity to be considered as ideal. In fact PSA is not specific for adenocarcinoma of the prostate: an elevated serum level of the marker does not necessarily mean malignant growth and normal levels too often hide an occult and potentially lethal cancer. With the discovery of different molecular PSA forms in the serum, an improved discrimination between benign prostate hyperplasia (BPH) and prostate cancer appears possible. This may be particularly useful in cases with equivocal PSA values and unpalpable prostate neoplasm to reduce the number of unnecessary prostate biopsies and increase the number of biopsies in cases without palpable or ultrasonic visible anomalies. The clinical use of PSA age-referenced levels is discussed. Their use is invaluable in screening programs where the routine adoption of age-specific values can help to pick-up younger patients with potentially curable prostate cancer and older patients with BPH where additional tests would be unnecessary. The role of PSA velocity (PASAV) s also discussed. An elevation rate of PSA of 0.75 ng/ml over 18 months on 3 serial samples appears to be the best cut-off to distinguish BPH from prostate cancer. However, the use of PSAV seems to be less useful in patients with elevated PSA levels and negative biopsy results. Free to total PSA ratio is probably the best parameter to reduce the number of unnecessary biopsies in men with a serum total PSA of 4 to 10 ng/ml. The advantages and limitations for different levels of cut-off are shown. A flow chart illustrating the role of various PSA "derivatives" in screening and subsequent evaluation of men over 50 years of age is also presented.

Relationship among symptom score, prostate volume, and urinary flow rates in 543 patients with and without benign prostatic hyperplasia.

BACKGROUND: Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS: A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS: As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS: We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume.

Hormonal profile of patients with Leydig cell tumors: a urologic cause of gynecomastia.

It is possible to hypothesize an alternative role for estrogens as a predisposing factor for testicular abnormalities: estrogen exposure during development in perinatal life may initiate cellular changes which would require estrogen and/or androgen later in life for promotion to hyperplasia or neoplasia. We reviewed the literature on Leydig cell tumors and the hormonal modifications they induce. In adult patients with Leydig cell tumors, although the serum estrogen (E2) and testosterone (T) varied, the T/E2 ratio was constantly low, and the chorionic gonadotropin administration produced an higher estrogen response than in normal men. Hormonal follow-up after orchidectomy for Leydig cell tumors has not been frequently described, and both normalization and lack of normalization of T, E2, gonadotropins and hCG have been reported. In the last part of the review we analyzed the principal urologic causes of gynecomastia in men. Testicular failure, either primary or secondary is a frequently found etiology for gynecomastia. Leydig cell tumors may elevate estrogen levels, and approximately 20% of patients with these tumors have gynecomastia.

Peptide growth factors: clinical and therapeutic strategies.

The literature contains many accounts of studies in which tumour growth has been accelerated by administration of a particular mitogen and the response then inhibited by co-administration of the corresponding antagonist. Much effort has been focused on the development of cytokine or growth factor antagonists. Like most other cancer therapies, biological therapies will undoubtedly have undesirable toxicities because the proteins they target may not be unique to malignant cells. We reviewed the clinical and therapeutic potential of growth factor agonists and antagonists in some non urologic and urologic diseases. In a recent report we demonstrated that both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor. Simultaneous treatment with 1 nM R1881 and 100 nM OH-Flutamide, completely counteracted the androgen-induced increase of Epidermal Growth Factor (EGF) levels. Moreover we found that Testosterone, DHT and EGF are mainly concentrated in the periurethral zone in human BPH and long term treatment with Finasteride and with Flutamide modify the distribution and concentration of these factors. Some authors analyzed whether and addition of aurin tricarboxylic acid (ATA) can reduce the growth rate of basic FGF-dependent cells in a manner similar to suramin.

DNA ploidy, Gleason score, pathological stage and serum PSA levels as predictors of disease-free survival in C-D1 prostatic cancer patients submitted to radical retropubic prostatectomy.

We report our experience with 85 prostatic cancer patients aged 51-79 years, who underwent radical retropubic prostatectomy from 1989 to December 1994 (mean follow-up 35 months). In order to get a more relevant analysis we chose to describe in detail only pathological C-D1 cases and to subdivide the patients, according to the Gleason sum, into G2-G5 and G6-G10 groups. Means of pre- and postsurgery PSA levels were ranked by DNA ploidy and presence or absence of recurrence: aneuploid patients showed lower levels of PSA production that may be due to cell dedifferentiation. However, in patients who developed recurrence, postsurgery PSA levels were higher (p < 0.005). The influence of DNA ploidy on disease-free survival was evaluated: the cumulative survival proportion was better in diploid (0.3581) than in aneuploid patients (0.2996). Using the Cox proportional hazard model with age, Gleason sum, DNA ploidy and presurgery PSA levels as covariates, we demonstrated that, in our series, only the presurgery PSA level was an important and significant predictor of recurrences (p < 0.005). Considering global recurrences with age, Gleason sum and presurgery PSA levels kept fixed, DNA aneuploidy conferred a relative risk 2.3 times higher than diploidy. When, in the same analysis, we introduced postsurgery PSA levels, only DNA ploidy and the latter variable kept statistical significance with a relative risk of 2.5. Considering only local and distant recurrences (with exclusion of those identified by elevated PSA levels) the relative risk was 3.9 and 3.8, respectively. These data support the critical role of nuclear DNA analysis as predictor of outcome after surgery even in this discussed subset of patients (C-D1).

Is medical therapy an expensive way for delaying surgery in BPH patients?

Nowadays, no medical therapy can be considered as a real and definitive alternative to surgery in the management of BPH patients. We considered pharmacologic approach as a treatment that may delay the need for surgery for BPH. In some cases a delayed therapy may continue for all patient life, excluding the need for TURP. The questions that we propose in the present review are: Is there always a role for a delayed medical therapy in the treatment of BPH patients? In which BPH patients a delayed medical therapy and in which instead an immediate surgery may be chosen? Which factors may influence this decision? A delayed medical therapy cannot be chosen in all BPH cases. Two factors can influence the evolution of the disease and the decision of the therapy: the first, natural history of BPH is related to BPH progression, and the second to patient characteristics. The role of growth factors in the natural history of BPH is investigated. Age of patient, his health condition and the presence of concomitant diseases are characteristics that may influence the therapeutic choice. In a young patient with good health condition and no concomitant diseases, the specific clinical phase of BPH is crucial to determinate the need for surgery of for medical delayed therapy. If there is a worsening health status or concomitant diseases as diabetes and hypertension that can increase the risk related to surgery in the future or can determine a more rapid evolution of BPH, TURP may be immediately recommended in all clinical phases of prostatic hyperplasia. The role of age in this therapeutic decision must be carefully examined.

Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?

The efficacy of radical prostatectomy on localized prostate cancer is well documented. However if a high risk for patients suffering from prostate cancer and effectiveness of treatment would be documented, the advantage of the therapy on the natural history of the disease must be demonstrated. Johansson et al. analyzed the natural history of 223 untreated localized prostate cancer with a mean follow up of 123 months. Only 8.5% of the patients died of prostate cancer. The 10 year disease specific survival rate was 86.8%. The progression free survival rate was 53.1%. Zincke et al. reported that the disease specific survival of the T1 T2 submitted to radical prostatectomy at 15 years was 93% and the survival free of disease was 70%. Our data on localized prostate cancer submitted to radical prostatectomy showed that the disease specific survival and the progression free survival after 5 years of follow-up were 99% and 85.7% respectively. Fleming, focusing on life expectancy, demonstrated that radical prostatectomy provides some benefit compared with watchful waiting for patients younger than 70 years. The greatest marginal benefits of treatment arise when we assume higher metastatic rates and higher treatment efficacy. In fact in this case, radical prostatectomy offers 3.5 years of improvement in quality of life adjusted survival in younger patients with moderately or poorly differentiated tumors. Radical prostatectomy can particularly benefit selected groups of patients with localized prostate cancer. The grade of differentiation has been shown to be the most powerful predictor in several series. DNA ploidy and tumor volume may be other reliable prognostic factors. Among all the parameters considered, the two with greatest effect in determining the outcome of treatment compared to watchful waiting were the rate of progression to metastatic disease in untreated patients and the estimated efficacy of treatment in reducing the metastatic rate.