Use of fosfomycin as targeted antibiotic prophylaxis before prostate biopsy: A prospective randomized study.

OBJECTIVES: To investigate whether switching ciprofloxacin to fosfomycin in the case of fluoroquinolone-resistant rectal bacteria influences the incidence of infectious complications after transrectal prostate biopsy. METHODS: From December 2015 until December 2017, patients undergoing prostate biopsy were randomly assigned to a control group or an intervention group in a prospective, open-label fashion at three different centers. The presence of fluoroquinolone-resistant organisms was detected by rectal swabs. Patients in the control group received ciprofloxacin. Patients in the intervention group received fosfomycin instead of ciprofloxacin in the case of fluoroquinolone-resistant bacteria on rectal swab culture. The primary end-point was the difference in occurrence of major (febrile) and minor (afebrile) infections between both groups. RESULTS: A total of 102 patients were randomized to the control group, and 102 patients to the intervention group. In the control group, nine complications occurred, of which five were major febrile complications. In the intervention group, six complications occurred, of which four were major febrile complications. The total number of complications (major and minor) did not differ between both groups (P = 0.59). A subgroup analysis of patients with fluoroquinolone-resistant bacteria on rectal swab showed five complications in the control group and one complication in the intervention group (P = 0.09). CONCLUSIONS: This represents the first prospective randomized study using rectal cultures for targeted antibiotic prophylaxis. Study findings show promising results for use of fosfomycin in patients with fluoroquinolone resistance.

Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro.

BACKGROUND: Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking. AIM: To evaluate the neurotropic effects of galanin receptor agonists and antagonists in vitro in nitrergic neurons and MPG and in vivo in rats after BCNI. METHODS: Male Sprague-Dawley rats underwent BCNI and sham surgery. Organ culture and single-cell neuron culture of the MPG were performed. Osmotic pump treatment with the galanin agonist in vivo and measurement of erectile response to electrostimulation after BCNI, immunohistochemical localization of galanin and receptors in the human neurovascular bundle, and myographic analysis of rat corpus cavernosum smooth muscle relaxation to galanin receptor agonists were investigated. OUTCOMES: Neurite outgrowth in vitro and erectile response to electrostimulation after BCNI in vivo, immunohistochemical localization of galanin and receptors, and penile muscle relaxation in vitro. RESULTS: Galanin showed neurotrophic action in vitro and inhibition of endogenous galanin significantly impaired neurite outgrowth in nitrergic but not in sympathetic MPG neurons. In vivo administration of a selective galanin receptor-2 agonist, M1145, resulted in partial recovery of erectile function (EF) after BCNI. Galanin did not act as a direct vasodilator on corpus cavernosum muscle strips. CLINICAL TRANSLATION: Endogenous neurotrophins such as galanin could be used as a strategy to improve EF for patients after BCNI from radical prostatectomy. STRENGTHS AND LIMITATIONS: We evaluated the effect of galanin on nerve regeneration and EF recovery in vivo and in vitro. Limitations include the lack of washout period for the in vivo experiment and absence of differences in the expression of neuronal markers between treatment groups. CONCLUSIONS: We identified galanin as a potential endogenous mechanism for nerve regeneration after BCNI, which could play a physiologic role in EF recovery after radical prostatectomy. In vivo treatment with exogenous galanin was beneficial in enhancing EF recovery after BCNI, but further research is necessary to understand the underlying mechanisms. Weyne E, Hannan JL, Gevaert T, et al. Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro. J Sex Med 2018;15:480-491.

Additive effects of the Rho kinase inhibitor Y-27632 and vardenafil on relaxation of the corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure.

OBJECTIVES: To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR]). Potent control subjects (n = 5) underwent penile needle biopsy. qPCR was performed for the expression of RhoA and ROCK subtypes 1 and 2. Immunohistochemistry staining against ROCK and α smooth muscle actin (αSMA) was performed on the corpus cavernosum of patients with ED. Tissue strips were precontracted with phenylephrine and incubated with 1 µm of the PDE5I vardenafil or with DMSO (control). Subsequently, increasing concentrations of the RKIs azaindole or Y-27632 were added, and relaxation of tissue was quantified. RESULTS: The expression of ROCK1 was unchanged (P > 0.05), while ROCK2 (P < 0.05) was significantly upregulated in patients with ED compared with controls. ROCK1 and ROCK2 protein colocalized with αSMA, confirming the presence of this kinase in cavernous smooth muscle cells and/or myofibroblasts. After incubation with DMSO, 10 µm azaindole and 10 µm Y-27632 relaxed precontracted tissues with 49.5 ± 7.42% (P = 0.1470 when compared with vehicle) and 85.9 ± 10.3% (P = 0.0016 when compared with vehicle), respectively. Additive effects on relaxation of human corpus cavernosum were seen after preincubation with 1 µm vardenafil. CONCLUSION: The RKI Y-27632 causes a significant relaxation of corpus cavernosum in tissue strips of patients with severe ED. The additive effect of vardenafil and Y-27632 shows that a combined inhibition of Rho-kinase and phosphodiesterase type 5 could be a promising orally administered treatment for severe ED.

Role and current situation of TURP in patients with elevated PSA.

OBJECTIVES: The aim of this review is to evaluate the place of transurethral resection of the prostate (TURP) in patients with elevated and/or rising prostate specific antigen (PSA). The role of TURP in these patients is assessed in symptomatic as well as in asymptomatic patients. METHODS: Current literature (1987-2009) was reviewed with regard to this specific population. This research was performed using the Medline online search tools. RESULTS: Initially, possible therapeutic strategies other than TURP could be used in patients with elevated and/or rising PSA values and no sign of proven prostate cancer. Consequently, the value of TURP in patients with elevated and/or rising PSA and no proven prostate cancer is discussed. In this setting, TURP can be executed with or without concomitant prostate biopsies. Furthermore, TURP can be proposed to patients with and without lower urinary tract symptoms. CONCLUSIONS: In this review, we evaluated the role of TURP in patients with elevated and/or rising PSA values and no proven prostate cancer. We believe TURP has a place in this particular population even in patients without lower urinary tract symptoms. This strategy is well founded on solid ground after an extensive review of the available literature. In most cases, a TURP will result in a normalization of PSA as well as a symptomatic benefit. Additionally, this procedure will allow histological evaluation which might show a possible life threatening prostate cancer in some patients.

Long-term clinical outcome of diagnostic transurethral resection of the prostate in patients with elevated prostate-specific antigen level and minor lower urinary tract symptoms.

INTRODUCTION: In patients with minor lower urinary tract symptoms (LUTS), elevated prostate-specific antigen (PSA) levels and (multiple) negative multi-site biopsies, therapy decision is complex. Long-term outcome of a diagnostic transurethral resection of the prostate (TURP) in these patients needs to be determined. METHODS: We retrospectively evaluated patients with minor LUTS, elevated PSA levels (>or=4 ng/ml) and no signs of prostate cancer. Patients with bladder outlet obstruction (BOO) underwent TURP. When TURP showed no malignancy, patients were annually evaluated by PSA testing and the International Prostate Symptom Score (IPSS). RESULTS: The study included 82 consecutive patients satisfying the inclusion criteria. All patients underwent TURP. No malignancy was encountered in 74 patients (90.2%). Of this group, 36 patients were followed >3 years (mean 62.1 months). One patient (2.8%) showed a persistently rising PSA level with positive extended multi-site biopsies 4 years after TURP, implying further treatment. 35 patients (97.2%) had a permanent complete normalization of PSA levels (<4 ng/ml) together with normalized IPSS. CONCLUSIONS: We consider an elevated PSA level in patients with minor LUTS and (multiple) negative multi-site biopsies as a sign of BOO. If these patients receive a diagnostic TURP, long-term outcome is excellent.

Prospective study of the role of transurethral resection of the prostate in patients with an elevated prostate-specific antigen level, minor lower urinary tract symptoms, and proven bladder outlet obstruction.

BACKGROUND: Deciding on strategy for patients with minor lower urinary tract symptoms (LUTS), elevated prostate-specific antigen (PSA) levels, unsuspicious digital rectal examination (DRE) and/or transrectal ultrasound (TRUS), and multiple negative extended prostate biopsies is complex. OBJECTIVES: To define the role and clinical significance of transurethral resection of the prostate (TURP) in these patients. DESIGN, SETTINGS, AND PARTICIPANTS: Thirty-three patients with elevated PSA; minor LUTS, as assessed by the International Prostate Symptoms Score (IPSS); no suspicion for prostate cancer on DRE and/or TRUS; and negative extended prostate biopsies were prospectively enrolled in a cohort study at a tertiary care institution. INTERVENTION: After full urodynamic investigation showing all patients to be bladder outlet obstructed, TURP was performed. MEASUREMENTS: Resected tissue was histologically examined for presence of prostate cancer. Within 6 mo after TURP, patients were clinically reevaluated by means of IPSS and PSA level. RESULTS AND LIMITATIONS: Preoperatively, mean PSA and IPSS values were 8.2ng/ml and 6.8, respectively. Mean detrusor pressure at maximum flow was 80.3cm H(2)O. Histological examination after TURP revealed benign prostate hyperplasia in 81.8% (subgroup 1) and aggressive prostate cancer in 6.1% of patients (subgroup 2). In 12.1% of patients, only a few chips of nonaggressive prostate cancer (T1a) were detected. In patients without signs of aggressive prostate cancer (93.9%=12.1%+81.8%, subgroup 3), mean postoperative PSA and IPSS values were 0.6ng/ml and 2.4, respectively, while these values were 0.6ng/ml and 2.5ng/ml in subgroup 1 (p<0.0001). This study is limited in sample size, requiring more research to confirm these results. CONCLUSIONS: This prospective study shows that, in patients with minor LUTS and no suspicion for prostate cancer, bladder outlet obstruction can result in elevated PSA levels. These patients will benefit from TURP regarding symptomatology and supernormalisation of PSA levels. Moreover, albeit in few cases, histological examination will reveal aggressive prostate cancer.

Rising PSA in patients with minor LUTS without evidence of prostatic carcinoma: a missing link?

OBJECTIVES: To determine the role of pressure flowmetry in patients without bothersome lower urinary tract symptoms (LUTS), rising prostate-specific antigen (PSA) levels and diagnosed as having clinical benign prostatic hyperplasia (BPH) after negative (multiple) extended multi-site biopsy. METHODS: The study enrolled patients with minor LUTS who were referred to our urological practice by their general practitioner because of a rising PSA level (>/=4 ng/ml). After exclusion of clinical prostatic carcinoma by digital rectal examination and transrectal ultrasound, all patients underwent at least one set of extended multi-site biopsies to exclude T1c prostate cancer. Patients with negative biopsies (clinical BPH) were subjected to pressure flowmetry whereafter those with bladder outlet obstruction underwent TURP. RESULTS: The study included 82 patients, with a mean age of 64.8 years (50.2-78.2 years), satisfying the inclusion criteria. Urodynamic analysis showed that all patients had bladder outlet obstruction. After TURP, eight patients (9.8%) were diagnosed as having histologically proven prostate cancer; 74 patients (90.2%) were diagnosed as having BPH. Patients of the BPH group had a mean preoperative PSA level of 8.8 ng/ml (4.3-25.8 ng/ml) and a mean international prostate symptom score of 8.8 (2-18). The mean detrusor pressure at maximum flow in BPH patients was 89.5 cmH(2)O (20-200 cmH(2)O). CONCLUSIONS: An increased PSA in patients with minor or no LUTS, clinical BPH and negative extended multi-site prostate biopsy is strongly correlated to bladder outlet obstruction. Therefore, patients with these characteristics should be treated with TURP.

Clinical relevance of transurethral resection of the prostate in "asymptomatic" patients with an elevated prostate-specific antigen level.

OBJECTIVES: To determine the clinical relevance of transurethral resection of the prostate (TURP) in patients with minor lower urinary tract symptoms (LUTS) but elevated prostate-specific antigen (PSA) levels. METHODS: We retrospectively included 82 patients, aged 50.2-78.2 yr, with minor LUTS, elevated PSA (> or =4 ng/ml), and no signs of prostate cancer (PCa) after (multiple) negative multisite biopsies who underwent TURP after they were diagnosed by urodynamics with bladder outlet obstruction (BOO). We evaluated the clinical benefit of TURP by assessing its effect on International Prostate Symptom Score (IPSS) and PSA and the diagnostic value of histologic examination of the resected tissue for the presence of PCa. RESULTS: After TURP, histologic analysis of the resected specimen revealed that eight patients (9.8%) had PCa; seven of these patients had a tumour that needed further treatment. The remaining 74 patients (90.2%) were diagnosed with BOO due to benign prostatic hyperplasia/benign prostatic enlargement (BPH/BPE). In this group, the mean PSA level decreased from 8.8 ng/ml before TURP to 1.1 ng/ml in the first year and 1.3 ng/ml in the second year after TURP; the mean IPSS decreased from 8.8 to 1.5 in the first year after TURP. CONCLUSIONS: The current data suggest that patients with minor LUTS and elevated PSA without evidence of PCa are very likely to have BOO due to BPH/BPE and may benefit from TURP if obstruction is proved. However, a prospective trial is warranted to assess the impact of these results on clinical practice.