A. Losa

Sildenafil taken at bedtime significantly increases nocturnal erections: results of a placebo-controlled study

OBJECTIVES Nighttime erections occur at all ages and contribute to the maintenance of the morphodynamic integrity of smooth muscle cells within the corpora cavernosa. This study was aimed at evaluating the effect on nocturnal erections of sildenafil versus a placebo taken at bedtime. METHODS A double-blind, crossover, placebo-controlled study design was used to examine the effects of sildenafil and placebo on sleep-related erectile activity. Thirty selected patients with erectile dysfunction (vasculogenic etiology, 22 patients [73%]; psychogenic etiology, 8 patients [27%]) were submitted to a polysomnographic recording of nocturnal erections, using a RigiScan device during 3 consecutive nights. After a first night of adaptation, the 2 following nights were used to study patients after the administration of sildenafil (100 mg) or a placebo taken at bedtime. RESULTS Twenty-three patients (77%) showed a significantly improved nocturnal erectile activity (according to the calculation of rigidity and tumescence activity units) after the administration of sildenafil (P <0.01), 5 patients (17%) showed comparable nocturnal erections with sildenafil and placebo, and 2 patients (6%) showed a significantly improved nocturnal erectile activity after taking the placebo (P <0.05). Overall, mean rigidity and tumescence activity values at the tip and base of the penis were significantly improved after sildenafil rather than placebo administration (P <0.001). The duration of tip rigidity greater than 60% was significantly longer during the night with sildenafil (P <0. 001). Although the number of erectile episodes was greater during the sildenafil night, this did not reach statistical significance. CONCLUSIONS In most patients with good sleep efficiency and who have erectile dysfunction, sildenafil, rather than a placebo, taken at bedtime produces a significantly improved nocturnal erectile activity. Further studies are needed to verify whether this preliminary finding may constitute the basis for the use of sildenafil as a tool for preventing erectile dysfunction.

Intravesical bacille Calmette-Guérin in stage T1 grade 3 bladder cancer therapy: a 7-year follow-up

OBJECTIVES To assess the long-term results of intravesical bacille Calmette-Guérin (BCG) treatment for Stage T1 grade 3 (T1G3) transitional cell carcinoma (TCC) of the bladder. METHODS Fifty-one patients with T1G3 TCC were treated with induction plus maintenance BCG courses after transurethral resection and followed up for at least 5 years or until death. RESULTS The median follow-up of progression-free patients was 85 months (range 64 to 108). During this period 32 (62.7%) of 51 patients remained progression free, 9 (17.6%) progressed, 8 (15.7%) died of other causes, and 2 (3.9%) were lost to follow-up. Seven patients had extravesical involvement: 5 (9.8%) of 51 had an upper urinary tract tumor and 3 (7.9%) of 38 had prostatic involvement (1 of the 7 had both). The risk of disease progression was significantly higher for patients with a tumor measuring 3 cm or more and those with tumor associated with carcinoma in situ (CIS) in multivariate analyses and for patients with recurrent tumors, solid tumors, or early T1G3 recurrence after BCG in univariate analyses. At last follow-up, 34 patients (66.7%) were alive; 8 (15.7%) had died of causes unrelated to the disease, 7 (13.7%) had died of bladder cancer, and 2 (3.9%) had been lost to follow-up. Disease-specific survival was 86.3%. CONCLUSIONS Intravesical BCG is an effective conservative treatment for T1G3 bladder cancer. Patients with negative prognostic factors such as coexisting CIS or large, solid, or recurrent tumor should be followed up closely and if T1G3 recurs early after the BCG induction course, immediate cystectomy should be performed.

LOW DOSE BACILLUS CALMETTE-GUERIN FOR CARCINOMA IN SITU OF THE BLADDER: LONG-TERM RESULTS

PURPOSE Bacillus Calmette-Guerin (BCG) is standard treatment for carcinoma in situ of the bladder. However, its long-term effectiveness is still debated. MATERIALS AND METHODS From January 1987 to January 1995, 70 consecutive patients with primary or secondary carcinoma in situ with or without concomitant solitary or multifocal papillary tumor were treated with weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after histological diagnosis. An additional induction course was given to patients with relapse. Tumor-free patients were given a maintenance course of monthly instillations for 12 months. RESULTS At the end of induction course 1, 56 of the 70 patients (80%) were tumor-free. Of 14 patients given induction course 2, 9 had a complete response (64.2%). A total of 65 patients (92.8%) were disease-free after 1 or 2 courses and given the maintenance course. Median followup for disease-free patients was 74 months (range 17 to 134). Subsequently 50 patients (71.4%) were disease-free, 12 (17.1%) had recurrence and 8 (11.4%) had progression. Mean time was 18 months (range 6 to 69) to treatment failure and 13 months (range 7 to 53) to progression. Of the patients 1 died of disease and 10 of other causes. Crude survival was 84.2%, disease specific mortality 1.4% and nondisease specific mortality 14.2%. The risk of treatment failure was significantly greater for carcinoma in situ associated with stage T1 papillary tumor (p = 0.0001) or severe dysplasia (p = 0.0005), and the risk of disease progression was significantly greater for carcinoma in situ associated with stage T1 papillary tumor (p = 0.0001). The drug was well tolerated with few side effects. CONCLUSIONS Intravesical BCG is the best available conservative therapy for patients with carcinoma in situ of the bladder. Low dose BCG is similarly effective, with a lower incidence of side effects and long lasting positive outcome.

Upper urinary tract tumors developing after treatment of superficial bladder cancer: 7-year follow-up of 591 consecutive patients

OBJECTIVES To evaluate upper urinary tract tumor (UUTT) incidence and characteristics in 591 consecutive patients with low-, intermediate-, or high-risk superficial bladder cancer, who were followed up for at least 5 years or until death. METHODS From 1986 to 1992, 591 patients were treated for superficial bladder cancer: 216 patients with primary, solitary, low-grade (G1-G2), and low-stage (Ta-T1) superficial bladder cancer were considered at low risk of disease recurrence and treated with transurethral resection (TUR) alone; 182 patients with recurrent or multifocal superficial bladder cancer were considered at intermediate risk of disease recurrence or progression and treated with intravesical chemotherapy after TUR; 193 patients with carcinoma in situ, high-grade (G3) superficial bladder tumor, or intravesical chemotherapy failure were considered at high risk of disease recurrence or progression and treated with bacille Calmette-Guérin (BCG). RESULTS After a median follow-up of 86 months (range 20 to 143), 2 (0.9%) of 216 patients at low risk, 4 (2.2%) of 182 patients at intermediate risk, and 19 (9.8%) of 193 patients at high risk developed UUTTs. The incidence of UUTTs is significantly higher in patients at high risk than in those at low risk (P = 0.0004, odds ratio = 11.6, 95% confidence interval [CI] 2.5 to 40.7) or at intermediate risk (P = 0.004, odds ratio = 4.8, 95% CI 1.5 to 17.2), or both (P = 0.000006, odds ratio = 7.3, 95% CI 2.6 to 20.3). The difference between patients at low risk and those at intermediate risk was not statistically significant (P = 0.5, odds ratio = 0.4, 95% CI 0.02 to 2.6). After a median time of 36 months (range 9 to 119) from UUTT diagnosis, 5 (20%) of 25 patients have died of the disease. CONCLUSIONS The incidence of metachronous UUTTs is low in patients with superficial bladder cancer at low or intermediate risk of disease recurrence or progression and significantly higher for patients at high risk. Because UUTT is often asymptomatic, and mortality is high, frequent and lifelong examination of the upper urinary tract is suggested, with an annual intravenous urogram and urinary cytologic analysis every 4 months in patients with superficial bladder cancer at high risk of disease recurrence or progression.

Low Dose Pasteur Bacillus Calmette-Guerin Regimen in Stage T1, Grade 3 Bladder Cancer Therapy

PURPOSE We assessed the effectiveness of intravesical bacillus Calmette-Guerin (BCG) for high risk transitional cell carcinoma of the bladder. MATERIALS AND METHODS A total of 51 patients with stage T1, grade 3 disease was treated with weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after transurethral resection for bladder cancer. An additional induction course was given to patients with relapse. Tumor-free patients followed a maintenance course with monthly instillations for 12 months. RESULTS After the initial induction course 37 of 51 patients (72.5%) remained tumor-free. A second induction course was necessary in 13 patients. After 1 or 2 induction courses 44 of 51 patients (86.3%) were tumor-free. The maintenance course was administered to 44 patients, with 41 remaining tumor-free. After a median followup of 33 months (range 3 to 63) 28 patients (54.9%) were disease-free, 12 (23.5%) had recurrent tumors and 7 (13.7%) had progression. The risk of treatment failure was significantly greater for solid than papillary tumors (p = 0.0006), recurrent than primary tumors (p = 0.0052) and coexisting carcinoma in situ (p = 0.124) in multivariate analysis, and for early recurrence (p = 0.0001) in univariate analysis only. The drug was well tolerated with few side effects. CONCLUSIONS Our data suggest that this low dose Pasteur BCG regimen is effective in the treatment of high risk superficial bladder cancer. Some tumor characteristics, such as solid appearance, coexisting carcinoma in situ, history of superficial transitional cell carcinoma and early relapse after the initial induction course, seem to be negative prognostic factors.

Laparoscopic Nerve- and Seminal-Sparing Cystectomy with Orthotopic Ileal Neobladder: The First Three Cases

INTRODUCTION AND OBJECTIVES Seminal and prostate sparing cystectomy represents an alternative in young patients where preservation of urinary continence and sexual potency are fundamental. We present our preliminary experience with this procedure performed laparoscopically. METHODS Three men-53, 58 and 49 years old-suffering from recurrent superficial transitional cell carcinoma of the bladder, resistant to intravesical therapy, underwent laparoscopic nerve, prostate and seminal vesical sparing cystectomy. One week before surgery, TURP was performed to create an adequate prostate capsule. After pneumoperitoneum induction and the positioning of five/six trocars, the ureters were clipped and transected, the vas deferens and seminal vescicles were identified and prepared for the conservative procedure. Cystectomy was performed with vascular pedicles transection by EndoGia. The reconstruction of the bladder was obtained through a 7 cm longitudinal periumbilical incision using 60 cm of ileus and an orthotopic neobladder realized outside the abdomen. The ileocapsular anastomosis was performed laparoscopically after the re-induction of pneumoperitoneum. RESULTS No major complications were recorded. The surgical time was respectively 480, 450 and 410 min. Blood loss was 150, 220 and 300 ml respectively. Drains were removed after 4 days (two patients) and 6 days (one patient) and the patients were discharged after 8 days (two patients) and 9 days. The patients were fully continent after catheter removal with normal uroflowmetry. At the three month follow-up they had a normal sexual function, equivalent to the preoperative assessment. The patients reported adequate erections for intercourse. CONCLUSIONS Laparoscopic prostate and seminal cystectomy with orthotopic ileal neobladder is a safe, feasible, reproducible surgical technique. In patients who desire to preserve sexual functioning and obtain complete continence it represents a valid alternative to classic radical cystectomy.

Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg

To evaluate the morphological changes induced by a 3‐month course of neoadjuvant bicalutamide 150 mg/day before radical prostatectomy (RP) on prostatic adenocarcinoma and high‐grade prostatic intraepithelial neoplasia (HGPIN).

Salvage brachytherapy for local recurrence after radical prostatectomy and subsequent external beam radiotherapy

OBJECTIVES To evaluate the technical feasibility, safety, and efficacy of seed implantation for local recurrence after radical prostatectomy and external beam radiotherapy. METHODS Between October 1999 and March 2002, 10 patients with targeted, histologically proven local relapse after surgery and subsequent external beam radiotherapy (only in 8 patients), underwent permanent brachytherapy with palladium-103 and iodine-125 after complete restaging. In all patients, an intraoperative morphovolumetric ultrasound study of the target was performed, with a planning target volume ranging from 5 to 26.7 cm(3). The preimplant prostate-specific antigen values ranged from 1.1 to 6.31 ng/mL. RESULTS Postplan dosimetry was performed to determine the percentage of the target volume that received a dose equal to, or greater than, the prescribed dose (range 84.5% to 95.9%) and the dose that was delivered to the 90% of the target volume (range 85.08% to 129.43%). The urinary scores, measured using the International Prostate Symptom Score, had normalized at 3 months. Only 1 patient had worsened incontinence during the first 2 months, with subsequent restoration of the previous situation. The other patients did not have any changes in their previous clinical condition. One patient experienced occasional gross hematuria that had been present after external beam radiotherapy. No rectal complications were reported. After a median follow-up of 20.6 months, 7 patients showed a decreasing or stable prostate-specific antigen level. CONCLUSIONS This preliminary experience has demonstrated that seed implantation of a neoplastic local recurrence is technically feasible and safe and allows for accurate dosimetry when the area to be treated can be defined by ultrasonography. Longer follow-up, accurate patient selection, and larger series of patients could help to better define the oncologic outcome.

Primary actinomycosis of the urachus.

Actinomyces israelii is an anaerobic Gram-positive bacA 22-year-old man was referred complaining of hypogastric pain of more than 5 months’ duration. Physical terium, a common commensal of the intestinal flora; infections are generally cervicofacial (63%), thoracic examination showed a hard, fixed, median umbilicalpubic mass infiltrating the abdominal wall. Blood chemis(15%) or abdominal (22%) and usually develop as a consequence of trauma, after surgical operations or in try tests showed no leucocytosis or abnormality in inflammatory index. An abdominopelvic contrastpatients with tumours [1]. Primary pelvic actinomycosis is extremely rare and diBcult to diagnose. Since medium CT scan showed a supravesical hypogastric mass of 6 cm, infiltrating the rectus abdominis muscles (Fig. 1). Henderson’s description of the relation between pelvic actinomycosis and intrauterine contraceptive devices The hepatic, splenic, pancreatic and renal parenchyma were normal. The initial suggestion was that the mass (IUDs), many cases of ‘pelvic inflammatory disease’ caused by Actinomyces have been reported among was a productive lesion starting from the urachus. The findings on cysto-urethroscopy were normal; a median women using the IUD [2,3]. However, this pathology rarely arises in the genito-urinary tract, but when it umbilicopubic laparotomy was then carried out and the mass, reaching from the umbilicus to the dome of the does it may cause mutilating lesions. Cases have been described of ureteric stenosis, and localization in the bladder, was excised. On gross inspection it contained reactive whitish fibrogranulomatous tissue surrounding bladder and retroperitoneum [4–6]. The variety of clinical presentations and the relative infrequency of the a central abscess (Fig. 2). Histological examination detected the typical bacterial colony (Fig. 3) which led to disease make diagnosis problematic. The radiological findings are not specific; CT can document the presence the diagnosis of actinomycosis. The patient was investigated to determine any possible origin of actinomycosis; no dental, mandibular, cardiac, thoracic or abdominal foci were found. The patient was treated with penicillin (20 MU intravenous infusion for 28 days) then amoxicillin (3 g/day orally for 6 months). The patient was followed as an outpatient and one year later is well.

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions

OBJECTIVE Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.