Preserved micturition after intradetrusor onabotulinumtoxinA injection for treatment of neurogenic bladder dysfunction in Parkinson's disease.

BACKGROUND: To assess the efficacy and safety of intradetrusor onabotulinumtoxinA (OnabotA) injection treatment in patients with neurogenic lower urinary tract dysfunction (NLUTD), especially for patients with Parkinson disease (PD). METHODS: PD patients refractory to oral antimuscarinic participated in an off-label use study and were evaluated prior and after 200 IU OnabotA injection into detrusor muscle, including trigone. Changes due to treatment were evaluated using bladder diaries, urodynamics, and questionnaires. Statistical analysis comprised Wilcoxon rank-sum test. Values are presented as mean ± standard deviation. RESULTS: Ten PD patients (4 female and 6 male, mean age: 67.9 ± 5.36 years) with LUTD were enrolled. All patients tolerated the treatment. Bladder diary variables decreased significantly (p ≤ 0.011) after OnabotA injection compared to variables prior injection. Desire to void and maximum bladder capacity increased significantly in urodynamics (p ≤ 0.05). Maximum detrusor pressure during voiding phase normalised from 56.2 to 18.75 cm/H20. Detrusor overactivity was less often detectable. All patients voided spontaneously. Mean post void residual (PVR) volume was 77.0 ± 119.78 mL postoperatively. No urinary retention or side effects have been observed during/after treatment. Mean follow-up time was 4 months (range of 1-12). 4 patients requested repeated injection after a mean period of 10 months between first and second injection. CONCLUSIONS: Our data confirm the efficacy and safety of 200 IU OnabotA injection in patients with neurogenic LUTD due to PD. The risk of urinary retention or high post-urinary residual volumes seems to be minor after OnabotA-injection. More research is needed with larger sample size to confirm the significance of these findings. TRIAL NUMBER: ISRCTN 11857462 , Registration Date 2016/10/08.

Cancer-specific and overall survival in patients with recurrent prostate cancer who underwent salvage extended pelvic lymph node dissection.

BACKGROUND: The aim was to evaluate cancer-specific survival (CSS) and overall survival (OS) in patients with prostate cancer (PCa) recurrence who underwent salvage extended pelvic lymph node dissection (ePLND), taking into consideration pre- and postoperative androgen deprivation therapy (ADT). METHODS: Salvage ePLND was performed in a cohort of 54 patients with PCa recurrence, and data from 45 patients were analyzed. The indications for salvage ePLND were biochemical recurrence (BCR) of PCa and suspect findings on (11)C-choline PET/CT. PSA-level, biochemical response (BR), duration of biochemical recurrence freedom (BCRF), number of metastases, OS and CSS were analyzed retrospectively. RESULTS: The average follow-up was 42.7 ± 20.8 months. Thirty-three patients (73.3 %, 95 % CI: 60.5-83.6 %) achieved BCRF during follow-up. The mean BCRF-period was 31.4 ± 19.7 months. CSS and OS were both 91.7 % ± 4.8 % (3-year survival) and 80.6 ± 8.6 % (5-year survival). Twenty-four patients (53.3 %, 95 % CI: 40.0-66.3 %) with castration-resistant PCa (CRPC) responded again to ADT after salvage ePLND. CONCLUSIONS: Salvage ePLND for selected patients with BCR and clinically recurrent nodal disease can achieve an immediate complete PSA response (i. e. BCRF) in nearly half of the patients. Patients with CRPC responded again to ADT after ePLND. Multicenter prospective studies with a control group are needed.

Establishment and characterization of primary cell lines of squamous cell carcinoma of the penis and its metastasis.

PURPOSE: We established cell lines from penile squamous cell carcinoma and its lymph node metastasis, and investigated the role of chemokines, chemokine receptors and podoplanin in cancer progression. MATERIALS AND METHODS: Tumor specimen of primary tumors, and lymph node and distant metastases were cultured in vitro and xenotransplanted in SCID beige mice. Specimens were analyzed by hematoxylin and eosin staining, and immunohistochemistry. Comparative screening for chemokines, chemokine receptors and podoplanin was done by polymerase chain reaction, fluorescence activated cell sorting and enzyme-linked immunosorbent assay. RESULTS: We established 2 cell lines from a primary tumor and its corresponding lymph node metastasis, respectively. Heterotopic xenotransplantation revealed reliable tumor growth in vivo. Morphological and immunohistological analysis showed comparable features for human tumors, cell lines in vitro and xenotransplanted tumors in mice regarding the primary tumor and metastasis. Comprehensive analysis of chemokines and chemokine receptors in the metastasis derived cell line and in the cell line originating from the primary tumor revealed the most pronounced changes for CXCL14. This pattern was confirmed on the protein level. Comparative analysis of podoplanin showed marked down-regulation in the metastatic variant on the mRNA and protein levels. CONCLUSIONS: To our knowledge we established the first pair of cell lines of a human primary penile tumor and the corresponding lymph node metastasis. These cell lines offer unique possibilities for further comparative functional investigations in in vitro and in vivo settings. They enable studies of new potential therapeutic agents and other assays to better understand the molecular mechanisms of penile cancer progression.

Interobserver variation in grading and staging of squamous cell carcinoma of the penis in relation to the clinical outcome.

OBJECTIVE: To examine interobserver variations in assessing grade and stage of penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: We retrospectively reviewed the pathological features and clinical outcome in 75 patients with SCC of the penis, who were treated in participating urological centres between 1996 and 2005; the assessments of the local pathologists and the review pathologists were compared. RESULTS: There was conformity in tumour grade in 67% and the assessment of tumour stage conformed in 84%; the combination assessment of both grade and stage conformed in 56%. CONCLUSION: Accurate histological subtyping by the surgical pathologist demands standardized guidelines, in particular for histological grading, which is crucial for clinical treatment, but shows significant interobserver variation.

Functional impact of the rhabdosphincter branch of the pelvic nerve on the membranous urethra in comparison to that of the pudendal nerve in male rabbits.

INTRODUCTION: The innervation of the membranous urethra (MU) is still under debate. We analysed the functional effects of electrostimulation of the rhabdosphincter branch of the pelvic nerve (RBP) on the MU in a standardized male rabbit model, paying attention both to the efferent and the possible afferent effects of stimulation. MATERIAL AND METHODS: Six male rabbits (chinchilla bastards) were included in this study. Pudendal nerve branches as well as pelvic nerve branches were exposed bilaterally in all animals. Randomized electrostimulation trials of both the pudendal nerve fibres and the RBP were carried out using a biphasic signal (0.3 mA, 200 mus). The stimulation frequency ranged from 10 to 40 Hz in a randomized pattern. Changes in MU pressure were measured urodynamically. The pressure changes occurring as a result of stimulation were compared in both nerve structures. At the end of the stimulation trial, the RBP and the pudendal nerve were dissected at different positions before repeating the stimulation and the MU pressure recording. RESULTS: The mean MU baseline pressure without stimulation was 24 cm H(2)O (range 21-27) in all animals. During unilateral pudendal stimulation, the mean pressure response rose by highly significant values (p < 0.005) compared to baseline. The pressure response was frequency dependent. Stimulation of the RBP resulted in a small but significant change of the MU pressure in the lower frequency range (10 and 20 Hz) (p > 0.05). On performing stimulation at higher frequencies, there was no significant difference from baseline. The pressure response of the MU during stimulation of the intact RBP did not differ significantly from the response after dissection of the RBP. However, after dissecting the pudendal nerve, the MU pressure response to RBP stimulation was diminished. CONCLUSION: Our results confirm the primacy of the pudendal nerve in the innervation of the MU. Stimulation of the RBP, however, may produce an afferent signal which is transmitted to the pudendal nerve, thus resulting in a pressure increase of the MU and contributing towards continence. We showed the importance of the RBP to maintain full urinary continence in rabbits. Our results suggest that substantially higher continence rates can be achieved through a nerve-sparing procedure in radical prostatectomy. Nerve-sparing radical prostatectomy incidentally also protects the RBP from injury.

Computer-aided (HistoScanning) biopsies versus conventional transrectal ultrasound-guided prostate biopsies: do targeted biopsy schemes improve the cancer detection rate?

OBJECTIVE: To define potential improvement in prostate cancer detection by application of a computer-aided, targeted, biopsy regimen using HistoScanning. MATERIALS AND METHODS: We analyzed 80 patients who underwent systematic transrectal, targeted transrectal, and targeted perineal biopsies. Each patient was diagnosed preoperatively by HistoScanning, defining a maximum of 3 suspicious areas. These areas were biopsied, both transrectally and via the perineum, with a maximum of 3 cores per location. RESULTS: We detected prostatitis in 30 patients (37.5%), premalignant lesions in 10 (12.5%), and prostate cancer in 28 (35%). The transrectal technique was used to detect 78.6% of all cancers using 14 cores by systematic biopsy. With a maximum of 9 targeted cores, 82.1% of all cancers were detected with the targeted perineal approach and 53.6% were detected with the targeted transrectal approach. Although our data did not show significant difference in the performance of targeted transperineal compared with systematic transrectal biopsies, the detection rate of targeted transrectal biopsies was significantly lower. CONCLUSION: The presented targeted biopsy scheme achieved an overall detection rate of 85% of prostate-specific antigen-relevant pathologic lesions within the prostate. Thus, the presented procedure shows an improved detection rate compared with standard systematic prostate biopsies, and the number of cores required is reduced. Furthermore, the perineal HistoScanning-aided approach seems to be superior to the transrectal approach with respect to the prostate cancer detection rate. The presented procedure might be a step toward reliable ultrasound-based tissue characterization and toward fulfilling the requirements of novel therapeutic strategies.

Functional outcome following photoselective vaporisation of the prostate (PVP): urodynamic findings within 12 months follow-up.

OBJECTIVES: We determined the impact of potassium-titanyl-phosphate (KTP) laser therapy of the prostate on urodynamic results, voiding function, quality of life, and sexual function. DESIGN, SETTING, AND PARTICIPANTS: Forty-five patients complaining of symptomatic benign prostatic hyperplasia (BPH) and urodynamically proven obstructive voiding were included in the prospective study. Follow-up exams were repeated 3 mo and 12 mo after the treatment. INTERVENTION: All patients underwent photoselective 80-Watt KTP laser vaporisation of the prostate performed by two experienced surgeons. MEASUREMENTS: Disease-specific quality of life and sexual function were assessed using the International Prostate Symptom Score (IPSS) and International Inventory of Erectile Function (IIEF). Video-urodynamics were carried out to determine changes in pressure flow and bladder function. RESULTS AND LIMITATIONS: The average preoperative prostate volume was 47.63 ml (range 30-75 m). The mean preoperative PSA-value, which had been 3.5 ng/ml (range 0.13-7 ng/ml) initially, dropped by 34.2% after 3 mo and 37.1% after 12 mo. Despite transient micturition complaints (40%), all patients showed significant improvement in the IPSS in urinary peak flow and detrusor pressure at peak flow. The mean post-void residual urine volume decreased, while erectile function and libido scores remained unaffected by the procedure according to the IIEF. Detrusor contractility was also not affected in any of the patients. The single-centre study design and small number of patients may have limited the study results. CONCLUSIONS: KTP laser therapy of the prostate achieves significant improvements both symptomatically as well as with respect to objective micturition parameters. The procedure leads to a functional deobstruction of the lower urinary tract with steady improvement results throughout the follow up period.