Andrea Salonia

Erectile Dysfunction Prevalence, Time of Onset and Association with Risk Factors in 300 Consecutive Patients with Acute Chest Pain and Angiographically Documented Coronary Artery Disease

OBJECTIVES The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease. METHODS 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments. RESULTS Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001). CONCLUSIONS Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.

Updated Nomogram Predicting Lymph Node Invasion in Patients with Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection: The Essential Importance of Percentage of Positive Cores

BACKGROUND Few predictive models aimed at predicting the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) are available to date. OBJECTIVE Update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS The study included 588 patients with clinically localised PCa treated between September 2006 and October 2010 at a single tertiary referral centre. INTERVENTION All patients underwent RP and ePLND invariably including removal of obturator, external iliac, and hypogastric nodes. MEASUREMENTS Prostate-specific antigen, clinical stage, and primary and secondary biopsy Gleason grade as well as percentage of positive cores were included in univariable (UVA) and multivariable (MVA) logistic regression models predicting LNI and formed the basis for the regression coefficient-based nomogram. The area under the curve (AUC) method was used to quantify the predictive accuracy (PA) of the model. RESULTS AND LIMITATIONS The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p<0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p≤0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively. The relatively low number of patients included as well as the lack of an external validation represent the main limitations of our study. CONCLUSIONS We report the first update of a nomogram predicting the presence of LNI in patients treated with ePLND. The nomogram maintained high accuracy, even in more contemporary patients (87.6%). Because percentage of positive cores represents the foremost predictor of LNI, its inclusion should be mandatory in any LNI prediction model. Based on our model, those patients with a LNI risk<5% might be safely spared ePLND.

Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-center prospective randomized trial in patients with obstructive benign prostatic hyperplasia.

PURPOSE To our knowledge we report the first multicenter, prospective, randomized study comparing holmium laser enucleation (HoLEP) and transurethral prostate resection (TURP) for obstructive benign prostatic hyperplasia. MATERIALS AND METHODS From January to October 2002, 100 consecutive patients with symptomatic obstructive benign prostatic hyperplasia were randomized at 2 centers to surgical treatment with HoLEP (52 in group 1) or TURP (48 in group 2). Patients in the 2 groups were preoperatively assessed by scoring subjective symptoms questionnaires. Preoperative and perioperative parameters were also evaluated, the latter at 1, 6 and 12 months of followup. RESULTS At baseline all patients had obstruction (Schäfer grade greater than 2). At the 1, 6 and 12-month followups no statistically significant differences were observed between the 2 groups in terms of urodynamic findings and subjective symptom scoring. In the HoLEP group mean total time in the operating room +/- SD was significantly longer than for TURP (74 +/- 19.5 vs 57 +/- 15 minutes, p <0.05), while catheterization time (31 +/- 13 vs 57.78 +/- 17.5 minutes, p <0.001 and hospital stay (59 +/- 19.9 vs 85.8 +/- 18.9 hours, p <0.001) were significantly shorter in the HoLEP group. Transient stress and urge incontinence were more common in the HoLEP group, although at the 12-month followup results were comparable. The overall complication rate was comparable in the 2 groups. Erectile function was also maintained in the followup period from baseline in each group, as expected. CONCLUSIONS HoLEP and TURP were equally effective for relieving obstruction and lower urinary tract symptoms. HoLEP was associated with shorter catheterization time and hospital stay. At 1 year of followup complications were similar in the 2 groups.

Dynamics of male sexual arousal: distinct components of brain activation revealed by fMRI

The peripheral mechanisms of male sexual arousal are well known. Recently, neuroimaging techniques, such as PET or fMRI, allowed the investigation of the subjacent cerebral mechanisms. In ten healthy subjects, we have simultaneously recorded fMRI images of brain activation elicited by viewing erotic scenes, and the time course of penile tumescence by means of a custom-built MRI-compatible pneumatic cuff. We have compared activation elicited by video clips with a long duration, that led to sexual arousal and penile erection, and activation elicited by briefly presented still images, that did induce sexual arousal without erection. This comparison and the use of the time course of penile tumescence in video clips allowed to perform a time resolved data analysis and to correlate different patterns of brain activation with different phases of sexual response. The activation maps highlighted a complex neural circuit involved in sexual arousal. Of this circuit, only a few areas (anterior cingulate, insula, amygdala, hypothalamus, and secondary somatosensory cortices) were specifically correlated with penile erection. Finally, these areas showed distinct dynamic relationships with the time course of sexual response. These differences might correspond to different roles in the development and appraisal of the sexual response. These findings shed light on the psychophysiology of male sexuality and open new perspectives for the diagnosis, therapy, and possible rehabilitation of sexual dysfunction.

Multicentric Study Comparing Intravesical Chemotherapy Alone and With Local Microwave Hyperthermia for Prophylaxis of Recurrence of Superficial Transitional Cell Carcinoma

PURPOSE To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment, after complete transurethral resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS The study was designed as a prospective, multicentric, randomized trial. Eighty-three patients suffering from primary or recurrent superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41 patients, and MMC in combination with local microwave-induced hyperthermia, for 42 patients. For the combined approach, a new system, Synergo101-1 (Medical Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence. The safety evaluation end points included subjective and objective side effects and clinical complications. For the efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test for significance. Minimum follow-up time was 24 months. RESULTS Of the 83 randomly assigned patients, 75 completed the study according to the protocol and had valid cystoscopy results. Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group. CONCLUSION In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.

Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair.

CONTEXT Varicocele is a common condition, found in many men who present for infertility evaluation. OBJECTIVE To assess the effect of varicocelectomy on male infertility. EVIDENCE ACQUISITION A literature search was performed using Embase and Medline. Literature reviewed included meta-analyses and randomized and nonrandomized prospective (controlled and noncontrolled) studies. In addition, a new meta-analysis was performed. EVIDENCE SYNTHESIS Four randomized controlled trials reporting on pregnancy outcome after repair of clinical varicoceles in oligozoospermic men were identified. Using the random effect model, the combined odds ratio was 2.23 (95% confidence interval [CI], 0.86-5.78; p=0.091), indicating that varicocelectomy is moderately superior to observation, but the effect is not statistically significant. We identified 22, 17, and 5 prospective studies reporting on sperm concentration, total motility, and progressive motility, respectively, before and after repair of clinical varicocele. The random effect model combined improvement in sperm concentration was 12.32 million sperm per milliliter (95% CI, 9.45-15.19; p<0.0001). The random effect model combined improvement in sperm total and progressive motility were 10.86% (95% CI, 7.07-14.65; p<0.0001) and 9.69% (95% CI, 4.86-14.52; p=0.003), respectively. These results indicate that varicocelectomy is associated with a significant increase in sperm concentration as well as total and progressive motility. Prospective studies also show that varicocelectomy reduces seminal oxidative stress and sperm DNA damage as well as improving sperm ultramorphology. Studies indicate that a microsurgical approach to a varicocele repair results in less recurrence and fewer complications than other techniques. CONCLUSIONS Although there is no conclusive evidence that a varicocele repair improves spontaneous pregnancy rates, varicocelectomy improves sperm parameters (count and total and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology. The various methods of repair are all viable options, but microsurgical repair seems to be associated with better outcomes.

Long-Term Follow-up of Patients with Prostate Cancer and Nodal Metastases Treated by Pelvic Lymphadenectomy and Radical Prostatectomy: The Positive Impact of Adjuvant Radiotherapy

BACKGROUND Recent large, prospective, randomised studies have demonstrated that adjuvant radiotherapy (RT) is a safe and effective procedure for preventing disease recurrence in locally advanced prostate cancer (PCa) patients. However, no study has ever tested the role of adjuvant RT in node-positive patients after radical prostatectomy (RP). OBJECTIVE We hypothesised that adjuvant RT with early hormone therapy (HT) might improve long-term outcomes of patients with PCa and nodal metastases treated with RP and extended pelvic lymph node dissection (ePLND). DESIGN, SETTING, AND PARTICIPANTS This retrospective study included 250 consecutive patients with pathologic lymph node invasion. We assessed factors predicting long-term biochemical recurrence (BCR)-free and cancer-specific survival (CSS) in node-positive PCa patients treated with RP, ePLND, and adjuvant treatments between 1988 and 2002 in a tertiary academic centre. INTERVENTION All patients received adjuvant treatments according to the treating physician after detailed patient information: 129 patients (51.6%) were treated with a combination of RT and HT, while 121 patients (48.4%) received adjuvant HT alone. MEASUREMENTS BCR-free survival and CSS in patients with node-positive PCa. RESULTS AND LIMITATIONS Mean follow-up was 95.9 mo (median: 91.2). BCR-free survival and CSS rates at 5, 8, and 10 yr were 72%, 61%, 53% and 89%, 83%, 80%, respectively. In multivariable Cox regression models, adjuvant RT and the number of positive nodes were independent predictors of BCR-free survival (p=0.002 and p=0.003, respectively) as well as of CSS (p=0.009 and p=0.01, respectively). Moreover, there was significant gain in predictive accuracy when adjuvant RT was included in multivariable models predicting BCR-free survival and CSS (gain: 3.3% and 3%, respectively; all p<0.001). CONCLUSIONS Our data showed excellent long-term outcome for node-positive PCa patients treated with radical surgery plus adjuvant treatments. This study is the first to report a significant protective role for adjuvant RT in BCR-free survival and CSS of node-positive patients.

Validation of a nomogram predicting the probability of lymph node invasion based on the extent of pelvic lymphadenectomy in patients with clinically localized prostate cancer

To develop a multivariate nomogram to predict the rate of lymph node invasion (LNI) in patients with clinically localized prostate cancer according to the extent of extended pelvic lymphadenectomy (PLND), which is associated with significantly higher rate of LNI.

Combination of Adjuvant Hormonal and Radiation Therapy Significantly Prolongs Survival of Patients With pT2–4 pN+ Prostate Cancer: Results of a Matched Analysis

BACKGROUND Previous prospective randomised trials have shown a positive impact of adjuvant radiation therapy (RT) in patients with locally advanced prostate cancer. However, none of these trials included patients with lymph node invasion (LNI). OBJECTIVE The aim of this study was to assess the impact of combination adjuvant hormonal therapy (HT) and RT on the survival of patients with prostate cancer and histologically documented lymph node metastases (pN+). DESIGN, SETTING, AND PARTICIPANTS Data on 703 consecutive patients with LNI treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant treatments between September 1986 and November 2002 at two large academic institutions were reviewed. MEASUREMENTS For study purposes, patients treated with adjuvant HT plus RT and patients treated with adjuvant HT alone were matched for age at surgery, pathologic T stage and Gleason score, number of nodes removed, surgical margin status, and length of follow-up. Differences in cancer-specific survival (CSS) and overall survival (OS) were compared using the Kaplan-Meier method and life table analyses. RESULTS AND LIMITATIONS Following the matching process, 117 pT2-4 pN1 patients of 171 (68.4%) treated with adjuvant HT plus RT (group 1) were compared with 247 pT2-4 pN1 patients of 532 (46.4%) receiving adjuvant HT alone (group 2). After matching, the two groups of patients were comparable in terms of pre- and postoperative characteristics (all p ≥ 0.07). Mean follow-up was 100.8 mo (median: 95.1 mo; range: 3.5-229.3 mo). Overall, prostate CSS and OS rates at 5, 8, and 10 yr were 90%, 82%, and 75%, and 85%, 70%, and 60%, respectively. Patients treated with adjuvant RT plus HT had significantly higher CSS and OS rates compared with patients treated with HT alone at 5, 8, and 10 yr after surgery (95%, 91%, and 86% vs 88%, 78%, and 70%, and 90%, 84%, and 74% vs 82%, 65%, and 55%, respectively; p = 0.004 and p<0.001, respectively). Similarly, higher survival rates associated with the combination of HT plus RT were found when patients were stratified according to the extent of nodal invasion (namely, two or fewer vs more than two positive nodes; all p ≤ 0.006). Lack of standardised HT and RT protocols represents the main limitations of our retrospective study. CONCLUSIONS Adjuvant RT plus HT significantly improved CSS and OS of pT2-4 pN1 patients, regardless of the extent of nodal invasion. These results reinforce the need for a multimodal approach in the treatment of node-positive prostate cancer.

A Critical Analysis of the Role of Testosterone in Erectile Function: From Pathophysiology to Treatment—A Systematic Review

CONTEXT Androgen modulation of erectile function (EF) is widely accepted. However, the use of testosterone replacement therapy (TRT) in men with erectile dysfunction (ED) has generated an unprecedented debate. OBJECTIVE To summarize the relevant data on the incidence, diagnosis, and management of ED coexisting with hypogonadism and to develop a pathophysiology-based treatment algorithm. EVIDENCE ACQUISITION We reviewed the relevant medical literature, with a particular emphasis on original molecular studies, prospective observational data, and randomized controlled trials performed in the past 20 yr. EVIDENCE SYNTHESIS Testosterone modulates nearly every component involved in EF, from pelvic ganglions to smooth muscle and the endothelial cells of the corpora cavernosa. It also regulates the timing of the erectile process as a function of sexual desire, coordinating penile erection with sex. Epidemiologic studies confirm the significant overlap of hypogonadism and ED; however, most guidelines do not consider the differential diagnosis of hypogonadism or the relevance of subclinical disease. Various clinical tools can help the physician to assess and restore androgen levels in men with ED. Special attention is given to fertility-sparing treatments, due to the increasing number of older men desiring fatherhood. The simultaneous use of phosphodiesterase type 5 inhibitors (PDE5-Is) and TRT has recently been questioned. Originally proposed as a salvage therapy for nonresponders to PDE5-Is, this approach has been inappropriately transformed into a combination therapy. Clinical data are consistent when reinterpreted in the proper framework, whereas molecular evidence remains controversial. CONCLUSIONS A body of molecular and clinical evidence supports the use of TRT in hypogonadal patients with ED, although the benefit-risk ratio is uncertain in advanced age. Critical appraisal of this evidence enabled the development of a pathophysiology-oriented algorithm designed to avoid inappropriate treatments and support whether to start with TRT, PDE5-I only, or both. Apparently divergent findings are reconciled when TRT is correctly indicated. An improved diagnosis and individualized management is desirable in light of the many available options.