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.

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.

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.

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.

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.

Combination of intravesical chemotherapy and hyperthermia for the treatment of superficial bladder cancer: preliminary clinical experience.

The prevalence of superficial transitional cell carcinoma of the bladder (STCCB) is still increasing in spite of improved adjuvant chemotherapeutic and/or immunoprophylaxis approaches. Thus, there is certainly an urgent need to improve our ability to control this disease. Local hyperthermia has a therapeutical potential for the treatment of many solid tumors, especially when used in combination with other treatments, such as radiation and chemotherapy. In particular, a synergistic or, at least, supra-additive anti-tumor cell killing effect was documented when local hyperthermia was administered in combination with selected cytostatic drugs. Recently, advances in miniaturized technology have allowed the development of a system specifically designed for delivering an endovesical thermo-chemotherapy regimen in humans. In preliminary clinical experiences, insofar mainly carried out as mono-institutional investigations, the combined treatment using this system was demonstrated to be feasible, minimally invasive and safe when performed on out-patient basis. Moreover, the anti-tumoral efficacy seemed to be significantly enhanced when compared with that obtained using intravesical chemotherapy alone for both adjuvant (prophylaxis) and neo-adjuvant (ablative) approaches to superficial bladder cancer.

Pharmacological management of erectile dysfunction.

Pharmacological treatment of erectile dysfunction includes all therapeutic modalities based on the use of erectogenic drugs, regardless of the route of administration. Intracavernous vasoactive injection therapy is the most commonly used treatment for erectile dysfunction. Most patients respond to intracavernous injection of either single or multiple vasoactive drugs. Major adverse effects related to this treatment include priapism, corporeal pain and the formation of nodules or plaques in the corpora cavernosa. Oral administration of drugs aimed at improving erectile function has not produced results comparable with those obtained with intracavernous injection therapy. However, in patients with psychogenic or mild organic impotence, oral treatment with drugs that influence either central or peripheral pathways controlling erection may improve erectile function. Topical administration of vasoactive drugs in the form of gels, liquid solutions or plasters is another attractive alternative for the treatment of psychogenic and mild organic erectile dysfunction. Although the ideal drug for the treatment of erectile dysfunction has not yet been identified, extensive laboratory and clinical research is ongoing and successful results are expected in the near future.

Cardiac autonomic nervous activity in sleep-related painful erections.

Sleep-related painful erections (SRPE) are characterized by penile pain that occurs during erections, typically during REM sleep. Afflicted individuals usually have normal erections during wakefulness. The disorder could be related to an altered autonomic function only during sleep. The aim of this study was to evaluate tonic and phasic heart rate (HR) modifications during sleep in 10 SRPE patients compared to 25 age-matched controls. A reduced cardiac vagal activity during sleep, as well as a trend towards a higher HR acceleration in relation to spontaneous body movements, have been found in SRPE patients. The possible beta-adrenergic hyperactivity during sleep in these patients could explain the reported efficacy of a beta-blocker, such as propranolol, in this disorder.

Laparoscopic bilateral adrenalectomy for persistent Cushing's disease after transsphenoidal surgery.

BACKGROUND: We performed bilateral laparoscopic adrenalectomies on four patients (three women and one man) with Cushing's disease (pituitary-dependent Cushing's syndrome) showing persistent hypercortisolism after transsphenoidal surgery. METHODS: The technique for bilateral transperitoneal laparoscopic adrenalectomy was derived from the one previously adopted by our group for unilateral adrenalectomy and previously described. Eight trocars were used, of which two were used for both left and right adrenalectomy. RESULTS: Bilateral laparoscopic adrenalectomy was performed in a one-stage procedure in the three women and, because of the abundant abdominal fat of the patient, in a two-stage procedure (after a 1-week interval) in the man. Operating times for the three women were 255 minutes, 230 minutes, and 220 minutes, and for the man 170 minutes for right adrenalectomy and 140 minutes for left adrenalectomy. No surgical or anesthesiologic complications were encountered. All patients were discharged from the hospital within 5 days after operation. At present, after follow-up periods of 23, 8, 6, and 18 months, all patients show remission of Cushing's disease and undetectable cortisol levels. CONCLUSIONS: Our experience suggests that bilateral laparoscopic adrenalectomy is a safe and effective procedure and a valid therapeutic option in patients with Cushing's disease showing persistent hypercortisolism after transsphenoidal surgery. However, the decision to remove both adrenal glands in such patients needs to be weighed against the risk of their having Nelson's syndrome or other long-term complications.

Laparoscopic unroofing of simple renal cysts.

OBJECTIVE: The aim of this study was to assess the clinical reliability of laparoscopic treatment for simple renal cysts. METHODS: Twenty patients with symptomatic simple renal cysts underwent laparoscopic unroofing of the cysts. Four of these patients also underwent concomitant laparoscopic cholecystectomy because of symptomatic gallbladder stones. RESULTS: In all cases the cyst wall was widely resected with no significant surgical complication. Cholecystectomy was easily performed without additional morbidity. Postoperative renal ultrasonography and intravenous urography demonstrated the absence of cyst recurrences and the integrity of the excretory tract. Symptoms were resolved by the operation in all cases. CONCLUSIONS: Laparoscopic unroofing is a safe, effective, and minimally invasive treatment for selected symptomatic simple renal cysts.

Pathologic features and clinical outcome after anatomic radical prostatectomy by transcoccygeal approach.

OBJECTIVES: A nonrandomized prospective study was conducted aimed at verifying the clinical outcome and pathologic features of a group of patients submitted to transcoccygeal radical prostatectomy. METHODS: Radical transcoccygeal prostatectomy was performed at our institution in 26 patients after laparoscopic (24 cases) or open surgical (2 cases) pelvic lymphadenectomy. Eighteen patients were selected because they were considered to be at risk for nodal metastases on the basis of preoperative staging (prostate-specific antigen level of 20 ng/mL or greater and/or Gleason score greater than 5); the remaining 8 manifested incidental prostate carcinoma. RESULTS: Intraoperative complications included rectal injury in 1 patient (3.8%) and massive blood loss in another. Transitory leakage at the site of the urethrovesical anastomosis and urethrorectal fistula occurred postoperatively in 2 patients. The rate of positive surgical margins was 26.9%. The mean follow-up time is 27 months (range 3 to 39 months). Total urinary continence was obtained in 21 patients (80.8%); 5 patients (19.2%) still require urinary pads. Four patients (15.4%) have experienced tumor recurrence evidenced only by increased serum prostate-specific antigen levels. Local tumor recurrence with positive biopsy of the urethrovesical junction was diagnosed in 3 patients (11.5%), and 1 (3.8%) experienced systemic tumor recurrence. CONCLUSIONS: Radical transcoccygeal prostatectomy is a safe procedure for the surgical treatment of prostate cancer, both from a clinical and a pathologic point of view. Operative complication as well as pathologic features and clinical outcome reported in this series of patients must be related to selection criteria used in most cases. The exact role of radical transcoccygeal prostatectomy in the clinical setting has yet to be defined. According to these preliminary results, radical transcoccygeal prostatectomy should be further investigated in the treatment of incidental carcinoma after transurethral resection of the prostate or suprapubic prostatectomy and could become an elective indication in such cases.

An original balloon-expanding urethral suture guide for radical prostatectomy.

Between August 1991 and July 1994, an original balloon-expanding urethral suture guide (24 F) was used in 157 consecutive cases of radical retropubic prostatectomy. Both the instrument and its clinical use are described. This guide guarantees good intraoperative exposure of the sectioned urethral stump during vesical reanastomosis, thus improving the technical feasibility of radical prostatectomy.

Effectiveness and safety of multidrug intracavernous therapy for vasculogenic impotence.

A four-drug vasoactive mixture (papaverine hydrochloride, prostaglandin E1, phentolamine mesylate, atropine sulfate) was used for intracavernous injection therapy in 94 patients with vasculogenic impotence as diagnosed by color Doppler sonography and dynamic infusion cavernosometry-cavernosography. At a mean follow-up of twenty months, 66 patients (70%) are using the injections with the initial dose and are satisfied; 14 patients (15%) are using the injections with a smaller dose than initially given; and 14 patients (15%) dropped intracavernous treatment. Only 4 patients (4%) were unable to achieve a sustained rigid erection during the mixture titration phase. Selected cases of vasculogenic impotence can be safely and effectively treated by the association of drugs which rely on different mechanisms of action, producing a pharmacologic synergism which enhances the overall therapeutic effect.

Recombinant alpha interferon in metastatic renal cell carcinoma. A cooperative phase II study.

A total of 61 evaluable patients with advanced renal cell carcinoma have been treated with 3 x 10(6) IU per square meter of body surface with recombinant alpha 2b interferon three times a week within a Cooperative Phase II Study. Toxic death for terminal renal failure occurred in 1 patient (1.63%), and toxicities greater than WHO grade 2 were present in 10 cases (16%). The overall response rate after six months of treatment was 13.1% (partial response 4, minor response 4). Two complete responses were obtained at nine and fifteen months (3.3%). Long-lasting stabilization of disease was 13.1 percent.

Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The aim of this study was to determine the effectiveness and safety of yohimbine and trazodone used together for the treatment of pure psychogenic impotence. METHODS: Sixty-three patients who had psychogenic impotence diagnosed on the basis of sexual history, results of physical examination, laboratory analysis, polysomnographic recording of nocturnal erections, and dynamic color Doppler sonography of the cavernosal arteries were entered into a randomized, double-blind, placebo-controlled, partial crossover study comparing placebo with yohimbine (15 mg per day orally) and trazodone (50 mg per day orally) used together. Treatment consisted of two 8-week courses. Patients who initially received placebo for 8 weeks were then switched to the 2-drug combination for 8 weeks. Erectile function, ejaculation, interest in sex, and sexual thoughts were investigated at the end of drug treatment and at 3- and 6-month follow-up. For statistical analysis chi-square, McNemar, and Student's t test for unpaired data were used. RESULTS: Fifty-five patients (87%) completed the whole treatment schedule. Positive clinical results (complete and partial responses) were obtained in 39 (71%) patients at the end of the drug treatment phase. These results were significantly better than those obtained with placebo (p < 0.01). Positive results were maintained in 32 (58%) and 31 (56%) patients at 3- and 6-month follow-up, respectively. Minor drug-related adverse effects occurred in 6 (11%) of the patients in the yohimbine-trazodone group and in 2 (4%) in the placebo group. CONCLUSIONS: The combination of yohimbine and trazodone is a safe and effective first-line treatment for psychogenic impotence.

Intravesical electromotive administration of drugs for treatment of superficial bladder cancer: a comparative Phase II study.

OBJECTIVES: To evaluate the efficacy of electromotive administration (EMDA) of intravesical mitomycin-C (MMC) in patients with superficial bladder tumors and to evaluate the toxicity of the treatment. METHODS: Thirteen patients with multifocal Stages Ta-T1 and G1-G2 transitional cell carcinoma (TCC) of the bladder, primary or recurrent (group A), received MMC 40 mg (retained in the bladder for 2 hours) once a week for 8 weeks. Fifteen patients with the same characteristics (group B) were treated with EMDA/MMC at a current of 15 mA for 20 minutes once a week for 8 weeks. All lesions in the bladder except one (marker) were resected in each patient. RESULTS: In group A, 5 of 12 patients (41.6%) demonstrated complete macroscopic and histologic disappearance of the marker lesion (complete response [CR]). In group B, 6 of 15 patients (40%) had a similar CR. Recurrence rate in responders was 60% in group A versus 33% in group B after 7.6 and 6 months, respectively. Disease-free interval was 14.5 months in the EMDA/MMC group compared to 10.5 months in the MMC group. Side effects were few. CONCLUSIONS: In intermediate risk patients with TCC of the bladder, EMDA/MMC was not superior to MMC alone with a CR rate of 41% versus 41.6%. In responders, a lower recurrence rate and a longer disease-free interval were observed in the EMDA/MMC group.

Current status of local penile therapy.

Guidelines for management of patients with erectile dysfunction indicate that intraurethral and intracavernosal injection therapies represent the second-line treatment available. Efficacy of intracavernosal injections seems superior to that of the intraurethral delivery of drugs, and this may explain the current larger diffusion of the former modality. Safety of these two therapeutic options is well established; however, the attrition rate with these approaches is significant and most patients eventually drop out of treatment. Newer agents with better efficacy-safety profiles and using user-friendly devices for drug administration may potentially increase the long-term satisfaction rate achieved with these therapies. Topical therapy has the potential to become a first-line treatment for erectile dysfunction because it acts locally and is easy to use. At this time, however, the crossing of the barrier caused by the penile skin and tunica albuginea has limited the efficacy of the drugs used.