Fifteen-year single-centre experience with three different surgical procedures of nerve-sparing cystectomy in selected organ-confined bladder cancer patients.

OBJECTIVES: To evaluate technical feasibility and oncologic and functional outcomes of three different surgical procedures of nerve-sparing radical cystectomy (NS-RC) for the treatment of organ-confined bladder cancer at a single referral centre. MATERIALS AND METHODS: All consecutive cases of NS-RC carried out between 1997 and 2012 were retrospectively analysed. NS-RC included nerve-sparing cysto-vesicleprostatectomy (NS-CVP), capsule-sparing cystectomy (CS-C) and seminal-sparing cysto-prostatectomy (SS-CP). Peri-operative parameters and post-operative outcomes were analysed. RESULTS: Overall, 90 patients underwent NS-RC, 35 (38.9 %) of whom received a NS-CVP, while 36 (40 %) and 19 (21.1 %) underwent capsule CS-C and SS-CP, respectively. No difference was registered comparing oncologic outcomes of the three different techniques; however, two local recurrences after CS-C were attributed to the surgical technique. Complete post-operative daytime and night-time urinary continence (UC) at 24 and 48 months was achieved in 94.4 and 74.4 % and in 88.8 and 84.4 % of cases, respectively. CS-C showed both the best UC and sexual function preservation rate at early follow-up (24 months). Overall, a satisfactory post-operative erectile function (IIEF-5 ≥ 22) was proved in 57 (68.6 %) and 54 (65.0 %) patients at 24 and 48 months, respectively. Significant difference was found when comparing sexual function preservation rate of NS-CVP (28.5 %) to that of CS-C (91.6 %) and SS-CP (84.2 %). CONCLUSION: NS-RC for male patients accounted for 7.4 % of overall radical cystectomy. To a limited extent of the selected organ-confined bladder cancers treated, the three different procedures analysed showed comparable results in terms of local recurrence and cancer-specific survival. Both CS-C and SS-CP procedures provided excellent functional outcomes when compared to original NS-CVP.

Effects of Difaprost® on voiding dysfunction, histology and inflammation markers in patients with benign prostatic hyperplasia who are candidates for surgical treatment.

AIM: Although previous studies assessed the effects of Serenoa repens, quercetin and ß-sitosterol on inflammatory parameters, no randomized studies have tested the combination of these agents neither on BPH symptoms nor on the inflammatory pattern. The aim of this trial was to evaluate the effects of Difaprost® on voiding dysfunction, histological inflammatory alterations and apoptotic molecular mechanisms in BPH patients. METHODS: We included 36 patients affected by BPH with obstructive symptoms eligible for surgery. Patients were randomly assigned to two groups: 18 patients received Difaprost® for three months before surgery, and 18 patients did not receive any additional therapy and were scheduled for surgery. All patients receiving Difaprost® were evaluated with uroflowmetry with post-void residual volume (PVR) evaluation, serum PSA, and IPSS questionnaire before and after treatment. Moreover, we evaluated inflammatory patterns in prostatic specimens at final pathology. RESULTS: Even without statistically significant differences on inflammatory pattern between patients receiving Difaprost® and controls, patients receiving Difaprost® had lower presence of edema and angiectasia at histological evaluation of prostate specimens. Moreover, patients included in the treatment group had a clinically significant reduction of PVR (46.1 vs. 25.2 mL; P=0.1) and a slight increase in Qmed (5.6 vs. 6.5 mL/s; P=0.9) after three months of chronic treatment with Difaprost®. No statistically significant differences were recorded in other clinical parameters between patients receiving Difaprost® and controls. CONCLUSION: Although not statistically significant, patients treated with Difaprost® showed an improvement in voiding function compared to controls (namely, an increase in Qmed and a reduction of PVR). Future trials with a larger number of patients and a longer treatment period could be necessary to evaluate the clinical efficacy of Difaprost®.

Extended pelvic lymph node dissection in prostate cancer: a 20-year audit in a single center.

BACKGROUND: We set to assess the impact of stage migration in prostate cancer (PCa) on the evolution of the pN1 rate and tumor characteristics in pN1 patients over the last two decades. PATIENTS AND METHODS: We evaluated 5274 PCa patients treated with radical prostatectomy and anatomically extended pelvic lymph node dissection (ePLND) between 1990 and 2010. Year-per-year trends of clinical and pathological characteristics were examined. Logistic regression analyses addressed predictors of pN1. RESULTS: The median number of lymph nodes (LNs) removed was 16.0. Overall, the pN1 rate was 13.8% and it decreased from 26.1% to 15.6% between 1990 and 2010 (P < 0.001). For the same period, the pN1 rate changed from 0% to 3% in the low-risk PCa, from 20% to 7% in the intermediate-risk PCa, and from 33% to 44% in the high-risk PCa (P ≤ 0.01). In pN1 patients, pre-operative cancer characteristics and the median number of positive LNs (three in 1990 versus two in 2010) did not significantly change overtime (all P ≥ 0.1). Year of surgery was not an independent predictor of pN1 (all P ≥ 0.06). CONCLUSION: Based on ePLND outcomes, contemporary patients with intermediate- and high-risk PCa's still harbor a significant LNI risk. In consequence, stage migration does not justify omitting or limiting the extent of PLND in these individuals.

Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters.

BACKGROUND AND PURPOSE: α1 -adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the α1 A -AR selective antagonist silodosin (compared to tamsulosin and prazosin) on ureter pressures in a rat model of ureter obstruction, and on contractions of human and rat isolated ureters. EXPERIMENTAL APPROACH: After ethical approval, ureters of male rats were cannulated beneath the kidney pelvis for in vivo ureteral intraluminal recording of autonomous peristaltic pressure waves. A partial ureter obstruction was applied to the distal ureter. Mean arterial blood pressure (MAP) was recorded. Approximate clinical and triple clinical doses of the α1 -AR antagonists were given intravenously. Effects by the α1 -AR antagonists on isolated human and rat ureters were studied in organ baths. KEY RESULTS: Intravenous silodosin (0.1-0.3 mg kg(-1) ) or prazosin (0.03-0.1 mg kg(-1) ) reduced obstruction-induced increases in intraluminal ureter pressures by 21-37% or 18-40% respectively. Corresponding effects by tamsulosin (0.01 or 0.03 mg kg(-1) ) were 9-20%. Silodosin, prazosin and tamsulosin reduced MAP by 10-12%, 25-26% (P < 0.05), or 18-25% (P < 0.05) respectively. When effects by the α1 A -AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, silodosin had six- to eightfold and 2.5- to eightfold better efficacy than tamsulosin or prazosin respectively. Silodosin effectively reduced contractions of both human and rat isolated ureters. CONCLUSIONS AND IMPLICATIONS: Silodosin inhibits contractions of the rat and human isolated ureters and has excellent functional selectivity in vivo to relieve pressure-load of the rat obstructed ureter. Silodosin as pharmacological ureter stone expulsive therapy should be clinically further explored.

Clinical and diagnostic assessment for therapeutic decisions in prostate cancer.

Due to the heterogeneity of prostate cancer (PCa) outcomes, there is a need for individualized treatment plans based on clinical and cancer characteristics. Recent advances in sophisticated imaging modalities have improved the ability to stratify patients according to their risk of PCa diagnosis and progression. This, in turn, has positively influenced the clinical decision making process. However, there is also an overuse of diagnostic imaging in the evaluation of PCa patients. Baseline diagnostic and re-staging evaluations need to be indeed personalized, in order to maximize the results and reduce unnecessary, lengthy and costly procedures. The aim of this review was to critically evaluate current international guidelines in order to identify clinical and diagnostic markers that might help clinicians in the selection of the most appropriate imaging approach. For this aim, different imaging modalities were analyzed in patients with newly diagnosed PCa, focusing on local, nodal and distant staging. Every step of staging was taken into consideration based on patient individualized risk, as defined by routinely available clinical variables. Second, different imaging techniques were also reviewed in the context of relapse after primary treatment, highlighting their utility and impact in the clinical decision making process. This review focuses mainly on conventional established imaging techniques, with an eye also to novel approaches that still need to be validated on large patient series.

Are Caucasian-European men delaying fatherhood? Results of a 7 year observational study of infertile couples with male factor infertility.

This study was aimed at assessing presence and predictors of a trend towards more advanced paternal age at presentation in a cohort of 1283 Caucasian-European infertile couples with male factor infertility (MFI) over a short time frame. Multivariate linear regression analysis tested the association between predictors [namely, partners' age, length of infertility at first presentation, patients' comorbidities as scored with the Charlson Comorbidity Index (CCI) and educational status] and patient's age at presentation. Using anova, patient's age at presentation (F ratio: 2.43; p = 0.024) and patients' educational status (χ(2) trend: 142.38; p < 0.001) significantly increased over time. In contrast, length of infertility at first presentation, CCI and partners' age did not significantly change over time (all p ≥ 0.05). Linear regression analyses showed that CCI, educational status and year of presentation were not correlated with patients' age at presentation (all p ≥ 0.05), whereas partners' age (ß = 0.170; p < 0.001) and length of infertility (ß = 0.123; p = 0.004) were independent predictors of delayed fatherhood. These results showed a significant shift towards advanced paternal age, but a non-significant increase of maternal age at first presentation among Caucasian-European infertile couples with MFI over a short time frame.

Does diabetes mellitus increase the risk of high-grade prostate cancer in patients undergoing radical prostatectomy?

The objective was to test the hypothesis that in patients with prostate cancer undergoing radical prostatectomy (RP), diabetic patients are at a higher risk of harboring a high-grade tumor than non-diabetic patients. We examined 2060 consecutive men who underwent RP between 2001 and 2009. Of them, 7.1% had type 2 diabetes mellitus (DM). A high-grade tumor was defined as having a Gleason score ≥ 8. Univariable and multivariable logistic regression analyses were used to test the relationship between type 2 DM and high-grade tumor. Mean patient age was 64 years (range: 45-85). Mean total PSA level was 9 ng ml(-1) (range: 1-89.5). A significantly higher percentage of diabetic patients had high-grade tumor on biopsy (16.3 vs 7.6%; P = 0.001) and on RP specimen (21.1 vs 11.7%; P = 0.001) in comparison with non-diabetic patients. In multivariable analyses, DM was an independent predictor of high-grade tumor on biopsy (odds ratio = 2.31, P = 0.001) and on final pathological specimen (odds ratio = 2.22, P = 0.002). In patients undergoing RP, those with type 2 DM had a higher risk of harboring a poorly differentiated tumor on final pathological examination.

Systematic extended and saturation prostate biopsy: when and how.

The increasing incidence of prostate cancer is manly due to the improvement of systematic transrectal ultrasound-guided prostate biopsy techniques. The objective of this review is to analyze the different approaches and the most common schemes used to perform prostate biopsy, the role of the anesthetic procedures, of the complementary imaging methods and the histological evaluation of the biopsy results. The actual indications to perform prostate biopsy have been also critically reviewed. We performed a review of the literature by searching Medline Database with the following key words: prostate cancer, diagnosis, trans-rectal ultrasound (TRUS), prostate biopsy, anaesthesia and prognosis. Prostate biopsy is always performed under transrectal ultrasound guidance with both transrectal and transperineal approach, with a minimal core number of 10. The extended protocols include lateral peripheral zone cores and cores from lesions found on palpation or imaging. Saturation biopsies should be performed only in case of repeat biopsies. The refinement of effective local anesthesia has allowed to increase the number of biopsies without important side effects. Complementary imaging methods might be adopted in order to reduce the number of unnecessary procedures .The histological issues related to the number and the location of cores are still matter of debate as important prognostic factors. According to international guidelines, the factors most involved in performing prostate biopsy still include suspicious digital rectal examination and PSA. Both the transrectal and the transperineal approach in prostatic biopsy are valid in term of detection rate and low incidence of side effects. The initial biopsy scheme in mainly extended, saturation biopsy has to be considered only in the repeat setting, with the eventual help of the complementary imaging methods. The histological issues has to be considered about patient's prognosis.

Prophylaxis of erectile function after radical prostatectomy with phosphodiesterase type 5 inhibitors.

Erectile dysfunction (ED) is one of the most challenging complications associated with radical prostatectomy (RP) for clinically localized prostate cancer. Currently, a broad spectrum of therapeutic options are available to improve sexual health after surgical treatment. Several basic science reports highlighted a potential role for phosphodiesterase type 5 inhibitors in the prevention of endothelial damage related to ischemia reperfusion and/or denervation following surgery. Recent studies have shown that pharmacological prophylaxis soon after RP can significantly improve the rate at which erectile function is recovered after surgery. Use of on-demand treatments for ED in patients who have undergone RP has been shown to be highly effective. In this context, pharmacological prophylaxis potentially may have a significantly expanded role in future strategies aimed at preserving postoperative erectile function. We analyzed the factors affecting erectile function after RP and evaluated the evidence suggesting the role of pharmacological prophylaxis and treatment of ED after surgery.

Open prostatectomy and the evolution of HoLEP in the management of benign prostatic hyperplasia.

Trans-urethral resection of the prostate (TURP) and other minimally invasive therapies are the most common surgical procedures used to treat benign prostatic hyperplasia today. However, many patients with a markedly enlarged prostate are often not amenable to these treatment options. In these patients open prostatectomy has been representing a viable and preferred treatment. Despite the morbidity of open enucleation is substantial, until recently no other options were available when the size of the prostate approached 100 g and beyond. The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to TURP and to open prostatectomy for patients with lower urinary tract symptoms (LUTS) due to large benign prostatic enlargement. In this manuscript, the development of HoLEP from the initial reports to the long-term follow-up data which demonstrate the effectiveness of the technique in treating patients affected by LUTS secondary to large adenomas has been reviewed. HoLEP seems to represent a valid alternative to both TURP and OP, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. In conclusion, HoLEP can be offered as the size-independent gold standard treatment of patients with LUTS due to benign prostatic enlargement.

Bilateral renal mass suggestive of cancer.

We present the case of a 44-year old man, presenting with acute left flank pain and gross haematuria, affected by bilateral renal mass and massive para-aortic and mediastinic lymphadenopathy, highly suspicious for metastatic renal cancer.

Medical therapy of prostate cancer. A review.

Androgen ablation or blockade of androgen action through the androgen receptor (AR) has been the cornerstone of treatment of advanced prostate cancer. The relative merits of monotherapy or combined androgen blockade (CAB) are still the subject of debate. Each treatment strategy/hormonal agent has favourable and unfavourable effects. Patients with advanced prostate cancer will clearly benefit androgen deprivation-based treatment for palliating their symptoms and for improving their quality of life (QOL). However, whether these therapies prolong survival when administered before there are symptoms caused by disease progression remains controversial. Data from multiple recent studies indicate that an earlier treatment in patient's disease course likely leads to better outcome, but it is not easy to predict the best timing of hormonal therapy for asymptomatic advanced disease. For the purpose of delaying the onset of androgen-independent growth of prostate cancer, different regimen of intermittent androgen blockade (IAB) have been applied to patients. The use of IAB is increasing but, despite theoretical advantages in terms of patient QOL, clinical studies have yet to prove superiority over continuous therapy. The role of androgen deprivation in combination with surgery or radiotherapy has been also evaluated. While neoadjuvant hormonal therapy (NHT) can significantly decrease the incidence of positive margins at the time of radical prostatectomy (RP), 3 months of treatment is not long enough to have any significant effect on biochemical recurrence rates. The results of studies investigating longer courses (8 months) of NHT are awaited. High-risk patients should be considered for early adjuvant hormonal therapy (AHT) after surgery, as they may be most likely to benefit. The rationale for the use of NHT in combination with radiotherapy is that it reduces tumour volume and therefore the amount of radiation therapy that is needed to treat the tumour. It has been found that 3-4 months of hormonal treatment reduces prostate volume by 25-50%. Intermediate-risk patients treated with NHT and concomitant hormonal therapy have been found to have a 94% freedom for biochemical failure after 4 years, suggesting that this group is the ideal patient population to receive short-term hormonal therapy in combination with brachytherapy. Several studies suggested the current consensus that patients with clinically localized or locally advanced high-grade tumours benefit from definitive radiation therapy and long-term AHT. The current treatment for advanced prostate cancer remains essentially palliative. However, an increased understanding of the heterogeneous nature of the disease, the mechanisms that lead to hormone-refractory prostate cancer (HRPC) has identified novel therapeutic targets and led to the development of selective new therapies, that may help to prolong survival and maintain QOL for patients with HRPC.

Diagnosis of prostate cancer. State of the art.

The widespread acceptance of prostate-specific antigen (PSA) measurement as an early detection method for prostate cancer (Pca), coupled with the recent heightened public awareness of Pca as a common disease, has led to an increase in the detection of Pca. It has been established that digital rectal examination (DRE) and PSA are the most useful front-line methods for assessing an individual's risk of Pca. In addition to an elevated PSA above 4 ng/mL and an abnormal DRE, the decision to proceed with TRUS-guided biopsy may also be supported by other factors. Determining the presence of a significant rise in PSA between tests, whether the degree of PSA is concordant with the size of the prostate, and age appropriate PSA may aid in the interpretation of this risk. Grayscale transrectal ultrasound (TRUS) has been established as the first choice imaging technique making it possible to take biopsies, measure the volume and obtain a general overview of the prostate. To improve, however, the TRUS detection rate of Pca, many ultrasonographic technique improvements have been introduced and continuously evaluated. As for prostate biopsy, in the prostate with visible lesions, lesion-guided biopsies only play a role in combination with systematic biopsies, while the systematic prostate biopsy scheme should at the present time include 10 or 12 cores according to prostatic weight. The other imaging techniques actually play a marginal role in Pca detection, but may be useful for staging newly diagnosed Pca or in patient re-staging in case of biochemical failure after radical treatment.

Diagnosis of local recurrence after radical prostatectomy.

In the long-term there is biochemical evidence of recurrent prostate carcinoma in approximately 40% of patients after radical prostatectomy (RP). Detecting the site of recurrence (local vs distant) is critical for defining the optimum treatment. Pathological and clinical variables, e.g. Gleason score, involvement of seminal vesicles or lymph nodes, margin status at surgery, and especially the timing and pattern of prostate-specific antigen (PSA) recurrence, may help to predict the site of relapse. Transrectal ultrasonography (TRUS) of the prostatic fossa in association with TRUS-guided needle biopsy is considered more sensitive than a digital rectal examination for detecting local recurrence, especially if PSA levels are low. Although it cannot detect minimal tumour mass at very low PSA levels (< 1 ng/mL) TRUS biopsy is presently the most sensitive method for detecting local recurrence. Nevertheless, the conclusive role of biopsy of the vesico-urethral anastomosis remains unclear. However, 111In-capromab pendetide scintigraphy and [11C]-choline tomography (which are better than conventional imaging for detecting metastatic tumour), have low detection rates for local disease and are considered complementary to TRUS in this setting. Patients with a high PSA after RP may be managed with external beam salvage radiotherapy. An initial PSA of < 1 ng/mL, Gleason score < 8 and radiation dose of 66-70 Gy seem to be key factors in determining success. Although a positive TRUS anastomotic biopsy may predict a better outcome after radiation therapy, the need to take a biopsy in the event of PSA failure remains under investigation. The value of salvage radiation to the prostatic bed for PSA-only progression after RP remains in question.

Laparoscopic treatment of adrenal diseases: 10 years on.

Since it was initially described in 1992 laparoscopic adrenalectomy (LA) has been gaining popularity amongst urologists and its range of applications has progressively widened. Ten years after the first report of LA this type of operation is presently considered to be the 'standard of care' for most adrenal diseases requiring surgery. We define the current role of laparoscopy in the management of surgical adrenal diseases, using a Medline search (1997-2002) to assess reports of LA, focusing on indications, approaches (transperitoneal and retroperitoneoscopic) and comparative analyses, taking particular care to evaluate operative duration, rate of conversion and transfusion, complications and hospital stay. With both approaches LA is safe and effective and, when compared with open surgery, offers the same functional results with all the advantages of minimally invasive surgery. We conclude that LA based on either approach should be considered the treatment of choice for benign adrenal lesions. Although very promising, conservative surgery and LA should still be evaluated in cases of malignancy.

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.

The ageing male and erectile dysfunction.

Erectile dysfunction is common in the ageing man and reliable therapies are needed. The pathophysiology of erectile dysfunction in this group mainly includes chronic ischaemia, which triggers the deterioration of cavernosal smooth muscle and the development of corporeal fibrosis. Assessing the ageing man with erectile dysfunction who seeks medical treatment should comprise a thorough medical and sexual history, a systemic and focused physical examination and selected blood tests. Oral drug therapy represents a safe and effective option for most ageing men.