Real-World Evidence of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: An Austrian Multicenter Study.

INTRODUCTION: Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel), thus changing treatment strategies in metastatic hormonesensitive prostate cancer (mHSPC). PATIENTS AND METHODS: We conducted the first real-world analysis comprising 97 mHSPC patients from 16 Austrian medical centers, among them 79.4% of patients received abiraterone and 17.5% darolutamide treatment. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney U test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). RESULTS: Of 83.5% patients with synchronous and 16.5% with metachronous disease were included. 83.5% had high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37%, and 24.3% of patients, respectively. Importantly, a nonsimultaneous onset of chemotherapy and ARPI, performed in 44.3% of patients, was associated with significantly worse treatment response (P = .015, HR 0.245). Starting ARPI before chemotherapy was associated with significantly higher probability for progression (P = .023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3 to 5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. CONCLUSIONS: Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should be administered simultaneously, however if not possible, chemotherapy should be started first.

Acidification of 24-hour urine in urolithiasis risk testing: An obsolete relic?

BACKGROUND: Recommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions. MATERIAL AND METHODS: We collected urine samples from ten healthy volunteers and prepared aliquots to be stored either at room temperature or 4 °C. Some aliquots were preserved using hydrochloric acid prior to storage, some thereafter, some using the BD Urine preservation tube and some were not preserved at all. Storage duration was 0, 24, 48 or 72 h. In all samples calcium, magnesium, phosphorus, creatinine, oxalate, citrate and uric acid were measured and compared to the according reference sample. RESULTS: We could not find any significant deviation for any of the analytes and preanalytical treatment conditions compared to the associated reference sample. CONCLUSION: Preservation of 24 h urine for the metabolic evaluation in stone formers might not be necessary for sample storage up to 72 h.

Cell-Free DNA and Neuromediators in Detecting Aggressive Variant Prostate Cancer.

BACKGROUND: Aggressive variant transformation in metastatic castration-resistant prostate cancer (mCRPC) represents an under-recognized phenomenon. There is an urgent need for non-invasive biomarkers to detect these variants and identify treatment alternatives. METHODS: A prospective observational pilot study in mCRPC patients receiving treatment with cabazitaxel (CAB) was conducted. Neuromediators were sequentially evaluated and their impact on disease endpoints calculated. Targeted next-generation sequencing (NGS) of cell-free DNA (cfDNA) was also performed in a highly pretreated subset of patients. RESULTS: 23 patients were included. Estimated effects indicate that neuron-specific enolase (NSE) levels at baseline may be correlated with overall survival (NSE unit 18.3 ng/ml: HR1.262 (95% confidence interval (CI) 0.985-1.616)) and that chromogranin A (CGA) may be correlated with progression-free survival (CGA unit 98.1 ng/ml: HR1.341 (95% CI 1.011-1.778)). cfDNA analysis revealed mutations annotated in prostate cancer (PCA) and small cell cancers (SCC). 1 patient showed elevated neuromediators along with annotated mutations in PCA and SCC, potentially indicating aggressive variant cancer. In 3 patients KIT mutations (e.g. pM541L, pV654A) known to be tissue-based biomarkers with level 1 evidence for the treatment with imatinib and sunitinib were found. CONCLUSIONS: Sequential analysis of neuromediators and targeted NGS of cfDNA provide insight for the estimation of tumor heterogeneity under therapy with CAB.

Abdominal sacrocolpopexy with Pelvicol xenograft and concomitant Burch colposuspension.

PURPOSE: To evaluate the efficacy of Pelvicol xenograft use during abdominal sacrocolpopexy to repair pelvic organ prolapse (POP). PATIENTS AND METHODS: A total of 27 consecutive women with symptomatic POP were included in this study. A POP-quantification system and International Continence Society classification were used. Functional and anatomical outcomes were assessed. Subjective outcomes and physical activity after surgery were evaluated due to modified quality of life questionnaire. RESULTS: Median follow-up was 21 months (range: 16 to 41 months). Twenty-four (89%) patients were available for anatomical and subjective evaluation. Preoperative POP-quantification classification was: stage I: 11.1%, stage II: 25.9%, stage III: 48.2%, and stage IV: 14.8%. Overall, pad usage significantly decreased (mean 4.8 vs 1 pads, P=0.001). Stress urinary incontinence significantly improved after surgery in nine women (P=0.001). An additional five women were completely continent. No de-novo incontinence developed. Six women with preoperative urinary retention improved in the amount of residual urine postoperative (mean 35 vs 165 mL). Failure rate was 8.3% at 3 and 11 months after surgery, requiring a second reconstruction. There was no graft related complications or graft rejections necessitating removal occurring. Response rate of the questionnaire was 67%. Two women reported no interference in physical activity after 2 postoperative months, five women after 5 months, and five women 1 year later. Pelvic pain (vaginal pain) was partly improved in eight patients, postoperatively, and ten patients had complete resolution of pain after surgery. CONCLUSION: This study demonstrates that abdominal sacrocolpopexy is an effective surgical treatment in correcting POP. The use of Pelvicol is associated with a high recurrence rate and increased failure rate compared to traditional sacrocolpopexy with mesh. Larger clinical trials to evaluate the functional and anatomical outcomes are needed.

Prospective Evaluation of Neuromediator Dynamics in Castration-Resistant Prostate Cancer Patients During Docetaxel.

AIM: Aim of the study was to detect small cell/neuroendocrine (SCNC) transformation in metastatic castration-resistant prostate cancer (mCRPC) that is a challenging procedure. We investigated the role of neuromediator dynamics as potential evidence of SCNC in patients undergoing docetaxel therapy. PATIENTS AND METHODS: A multi-institutional, prospective observational study was conducted. Patients undergoing docetaxel treatment were included. Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) were sequentially evaluated at predefined time points. Outcome measures were overall survival (OS), progression-free survival (PFS) and PSA nadir. RESULTS: Fifty-two patients were included. A general rise in CGA levels was observed. Patients with a high CGA rise (100%ULN: CGA ≥98.1ng/ml) between the 1st and 3rd cycle trended towards a decreased OS (p=0.0649) and showed a decreased PFS (p=0.0369). In multivariate analysis, continuous CGA rise correlated with PFS (p=0.0553; HR 1.136), but was not an independent predictor of OS. CONCLUSION: Patients with an early high CGA rise may demonstrate a subgroup with poor outcome due to underlying SCNC transformation. Monitoring of CGA appears to be an option worth considering.

Prospective, Controlled Study of Invasiveness and Post-Aggression Metabolism in Patients Undergoing Robotic-Assisted Radical Prostatectomy.

OBJECTIVES: To evaluate in a prospective, controlled, nonrandomized study the surgical stress and acute-phase systemic response in robotic-assisted laparoscopic prostatectomy (RALP) compared to open radical retro-pubic prostatectomy (ORRP) by measuring humoral mediators. METHODS: Forty consecutive patients undergoing either RALP or ORRP were prospectively included to assess the extent of systemic response. Blood samples were collected before surgery (T1), at the time of prostatectomy (T2), at the time of wound closure (T3), and 12 h (T4), 24 h (T5), and 48 h (T6) after surgery, and assayed for interleukins (IL-6 and IL-10), C-reactive protein (CRP), and hemoglobin. A 2-sided p < 0.05 was considered to indicate significance. RESULTS: Baseline levels of IL-6, IL-10, and CRP were comparable in both arms of the study. IL-6 and IL-10 increased in both groups during surgery and reached maximum levels at 12 and 24 h after surgery. The RALP and RRP groups differed significantly at T2 (p = 0.009), T3 (p = 0.046), T5 (p = 0.05) and T6 (p = 0.0007) for IL-6, and at T3 (p = 0.05) and T4 (p = 0.05) for IL-10. CRP levels differed significantly at 48 h postoperative (p = 0.0053). The maximum levels of all 3 mediators in the RALP group were significantly lower than those in the open surgery group. Patients in the RALP group experienced less pain from day 2 to 4 according to the Visual Analog Scale (p < 0.05). CONCLUSIONS: The study suggests that IL-6 and IL-10 are useful objective markers for surgical stress and that tissue trauma and activation of post-aggression metabolism seem to be less in RALP compared to ORRP.

Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review.

BACKGROUND: Limited data are available for the use of agents in metastatic castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide data during treatment with cabazitaxel (CAB), helping to improve the informed-consent process. PATIENTS AND METHODS: We retrospectively reviewed patients treated with fourth-line or beyond CAB for mCRPC after failure of previous therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223. The progression-free survival (PFS) and the overall survival (OS) were estimated using the Kaplan-Meier method and compared to published data based on a structured literature review. The hospitalization rate was recorded. Factors influencing 6-months OS were analyzed. RESULTS: Fifteen patients were identified at 4 institutions and included in the analysis. The median PFS was 104 days (range 47-397 days). The median time to death was 10 months (range 2-16). PFS and OS data are in accordance with 17 published patients so far. During the therapy, eleven (73%) of the patients were hospitalized. Prostate-specific antigen (PSA, 500 units; hazards ratio [HR] 1.491, 95% CI 1.000-2.0175), white blood cell count (HR 0.425, 95% CI 0.108-0.952), hemoglobin (HR 0.6014, 95% CI 0.2942-1.0758), and alkaline phosphatase (100 units; HR 1.0964, 95% CI 1.000-1.2859) correlate with 6-months OS. CONCLUSIONS: CAB beyond the third-line is often accompanied by hospitalization. PFS is a significant proportion of the median time of OS. The baseline laboratory might be a good indicator for the decision between CAB and best-supportive care.

Metal telescopic and Amplatz sheath dilation in nephrolithotomy.

INTRODUCTION: Comparison of Amplatz sheath percutaneous nephrolithotomy (Amplatz PCNL) and metal telescopic dilation PCNL (MTD PCNL) with respect to clinical outcomes and complications. MATERIALS AND METHODS: Single-institution retrospective chart review with 73 patients who underwent PCNL divided into two groups: Amplatz PCNL (n = 26) and MTD PCNL (n = 47). Efficacy (stone-free rate, residual stones, and surgical duration) and safety (transfusion rate and hemoglobin decrease) were evaluated. Complications were recorded and classified using the modified Clavien classification system. RESULTS: The two PCNL groups were similar regarding mean age, stone burden, side, stone location, and stone composition. There were no significant differences in surgery duration (101 ± 28 vs. 98 ± 30 min; P = 0.906), transfusion rate (3.9% vs. 4.3%; P = 0.382), and hemoglobin drop (0.9 ± 0.9 vs. 1 ± 0.7 g/dl; P = 0.424) for Amplatz and MTD PCNL, respectively. Stone-free rate (86% vs. 68%; P = 0.001) was significantly higher while residual fragments rate (37% vs. 60%; P = 0.001) was significantly lower in Amplatz PCNL compared to MTD PCNL. However, tube stay time (4.4 ± 1.8 vs. 5.8 ± 3.6 days; P = 0.005) and hospital time (8.6 ± 2.6 vs. 9.7 ± 5.5 days; P = 0.0001) were significantly longer in Amplatz PCNL compared to MTD PCNL. Clavien grading revealed a significantly higher rate of low-grade complications (I-III) for the MTD PCNL in comparison to Amplatz PCNL (10.6% vs. 3.9%, respectively; P = 0.011). There were no major complications and no tract dilation failure. CONCLUSION: The study demonstrates that Amplatz PCNL is a safe and effective procedure to remove large renal stones compared with MTD PCNL.

Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naïve castration-resistant prostate cancer.

BACKGROUND: Abiraterone Acetate (AA) represents a highly effective androgen-receptor (AR) axis targeted agent. Treatment with AA in castration-resistant prostate cancer (CRPC) may partly mediate neuroendocrine differentiation (NED) as an escape mechanism, which may have implications for the choice of sequential therapy in CRPC. We evaluated how treatment with AA influences circulating neuromediators chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (Pro-GRP) in chemotherapy-naïve CRPC patients. METHODS: We conducted an analysis in chemotherapy-naïve CRPC patients with clinical or radiographic progression of disease. A total of 35 patients were included at five institutions between February 2013 and December 2014. Sixteen of them had received AA. Serum samples were obtained before a docetaxel-based chemotherapy and analyzed in a reference laboratory. Univariable and multivariable analyses were performed to test the influence of AA treatment, its duration of treatment, and other clinicopathological variables on circulating neuromediators. RESULTS: CGA and NSE levels were above the upper limit of normal (ULN) in n = 20 (57.1%) and n = 13 (37.1%), respectively. Treatment with AA and duration of treatment were not associated with levels above the ULN (CGA and NSE) or higher levels (Pro-GRP) of neuromediators. CGA levels were associated with age (P = 0.092), lymph node metastasis (P = 0.014), duration of androgen deprivation therapy (ADT; P = 0.083), and intake of proton pump inhibitors (P = 0.069). Pro-GRP levels were significantly associated with PSA levels (P = 0.002). On multivariate analysis, CGA levels above the ULN were significantly correlated with ADT (P = 0.01) and intake of proton pump inhibitors (P = 0.03). CONCLUSIONS: Circulating neuromediators in chemotherapy-naïve CRPC patients were elevated in a high percentage of patients. ADT was found to be a relevant NED driver in this cohort. Our results may imply that patients with CRPC after first-line treatment with AA in CRPC are not at a higher risk for developing NED. The major limitation of the study represents the one-time analysis of neuromediators. Larger studies with serial blood measurements or biopsy analysis before and after treatment are needed to confirm our results.

Selective clamping under the usage of near-infrared fluorescence imaging with indocyanine green in robot-assisted partial nephrectomy: a single-surgeon matched-pair study.

PURPOSE: To present a single-surgeon matched-pair analysis to show the feasibility of combining the technique of selective clamping with usage of near-infrared fluorescence imaging in robot-assisted partial nephrectomy and to investigate short-term renal function outcomes. METHODS: Twenty-two patients underwent selective clamping partial nephrectomy with the application of indocyanine green (ICG). Out of this cohort, a matched-pair analysis for R.E.N.A.L. nephrometry parameter was employed for 15 exactly matching partners. Demographic, surgical, pathological and kidney function data were collected for the initial cohort, and matched-pair comparison was made between the subgroups retrospectively. RESULTS: Robot-assisted partial nephrectomy without clamping of the hilum was possible in 21 patients; in one patient, main artery clamping was necessary due to bleeding. Mean clinical tumor size was 37.7 mm. Mean selective clamping ischemia time was 11.6 min with an estimated blood loss of 347 ml. No intraoperative complications occurred, and postoperative complications (n = 4), including two major urological (urinoma, late-onset acute hemorrhage) complications, were found. There were no side effects of ICG administration. Matched-pair analysis for 15 patients showed similar demographic and surgical data without any significant differences in tumor characteristics. Comparing short-term renal function outcomes, significantly decreased estimated glomerular filtration rate reduction in the selective clamping group with an absolute loss of 5.1 versus 16.1 ml/min in the global ischemia cohort (p = 0.045) could be observed. CONCLUSIONS: Robot-assisted partial nephrectomy with selective clamping of the tumor feeding vascular branches is a promising technique for reduced ischemic renal trauma. This may lead to improved kidney function preservation.

Testosterone boosts for treatment of castration resistant prostate cancer: an experimental implementation of intermittent androgen deprivation.

BACKGROUND: The primary therapeutic target for non-organ-confined prostate cancer is the androgen receptor (AR). Main strategies to ablate AR function are androgen depletion and direct receptor blockade by AR antagonists. However, incurable castration resistant prostate cancer (CRPC) develops resistance mechanisms to cope with trace amounts of androgen including AR overexpression and mutation in the AR ligand binding domain. METHODS: The CRPC cell model VCaP derivative of a prostate cancer bone metastasis was used in vitro and in nude mice in vivo to examine the effects of immediate testosterone boost on CRPC cells. In addition, a testosterone tolerant cell model was established by incremental acclimatization of VCaP cells to 1 nM testosterone. The effects of androgen withdrawal and testosterone boosts on gene expression were assessed by quantitative real-time polymerase chain reaction, ELISA, and Western blots. Tumor cell proliferation was evaluated with a BrdU test. RESULTS: Testosterone boosts on CRPC VCaP cells eliminate tumor cells to a higher extent than androgen withdrawal in androgen tolerant cells. The pronounced decrease of tumor cell proliferation was accompanied by a marked downregulation of AR expression regarding full-length AR and splice variant AR V7. CONCLUSIONS: Acquiring castration resistance of prostate cancer cells by AR overexpression and amplification obviously sensitizes such cells to testosterone concentrations as low as physiological values. This introduces novel therapeutic means to treat CRPC with non-toxic measures and may find clinical implementation in intermittent androgen deprivation regimens.

Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results from the German compassionate-use programme.

BACKGROUND: Cabazitaxel (Cbz) is an approved second-line treatment in metastatic castration-resistant prostate cancer (mCRPC) following docetaxel therapy with a significant survival benefit compared with mitoxantrone. However, grade 3/4 toxicities were reported in 82% of patients. OBJECTIVE: To report on the safety results of mCRPC patients treated within a compassionate-use programme in Germany. DESIGN, SETTING, AND PARTICIPANTS: A total of 111 patients with a mean age of 67.9 yr (range: 49-81 yr) and progressive mCRPC were included. Patients had received a mean number of 12.7 ± 10.8 cycles (range: 6-69 cycles) of docetaxel with a mean cumulative dose of 970.9 mg/m(2); mean time from last docetaxel application to progression was 6.95 mo (range: 2-54 mo). Of the patients, 31.5% progressed by prostate-specific antigen (PSA) increase only; the remainder had a combination of PSA increase and clinical progression. INTERVENTION: Cbz at a dosage of 25mg/m(2) intravenously every 3 wk combined with 5mg of oral prednisone twice a day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Treatment-associated toxicity was the primary study end point; progression-free and overall survival were secondary end points. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Patients received a mean number of 6.5 ± 2.2 cycles of Cbz and a mean cumulative dose of 160.3 ± 51.5mg/m(2). Grade 3 and 4 treatment-emergent adverse events were recorded in 34 patients (30.6%) and 18 patients (16.2%), respectively. Grade 3/4 anaemia, neutropenia, and thrombocytopenia were reported in 4.5%, 7.2%, and 0.9% of the patients, respectively. Neutropenic fever was reported in 1.8% of the patients. Grade 3/4 gastrointestinal toxicity was identified in 4.5% of the patients. Three patients died because of Cbz-related toxicity. Granulocyte colony-stimulating growth factors were used in 17.1% of patients. The limitations are due to the nonrandomised nature of the trial. CONCLUSIONS: Treatment with Cbz is tolerable and is associated with a low incidence of serious adverse events in a real-world patient population with CRPC. The outcome of serious adverse events can be minimised with proactive treatment management and conscientious monitoring.

Leiomyoma of the tunica albuginea, a case report of a rare tumour of the testis and review of the literature.

BACKGROUND: Leiomyomas are benign tumours that originate from smooth muscles. They are often seen in the uterus, but also in the renal pelvis, bladder, spermatic cord, epididymis, prostate, scrotum or the glans penis. Leiomyomas of the tunica albuginea are extremely rare. CASE PRESENTATION: A 59-year-old white male has noted an asymptomatic tumour on the right side of his scrotal sac for several years. This tumour has increased slowly and caused local scrotal pain. An inguinal incision was performed, in which the hypoplastic testis, the epididymis and the tumour could be easily mobilized. Macroscopically the tumour showed a solid round nonencapsulated whorling cut surface. Histologically the diagnosis of a leiomyoma was made. CONCLUSION: We report here a very interesting and rare case of a leiomyoma of the tunica albuginea. Leiomyomas can be a possible differential diagnosis in this area. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2585095378537599.

Radical prostatectomy after previous transurethral resection of the prostate: robot-assisted laparoscopic versus open radical prostatectomy in a matched-pair analysis.

PURPOSE: To determine whether previous transurethral resection of the prostate (TURP) compromises the surgical outcome and pathologic findings in patient who underwent either radical robot-assisted laparoscopic prostatectomy (RALP) or open retropubic radical prostatectomy (RRP) after TURP, because TURP is reported to complicate radical prostatectomy and there are conflicting data. PATIENTS AND METHODS: From July 2008 to July 2010, 357 patients underwent RALP. Of these, 19 (5.3%) patients had undergone previous TURP. Operative and perioperative data of patients were compared with those of matched controls selected from a database of 616 post-RRP patients. Matching criteria were age, clinical stage, the level of preoperative prostate-specific-antigen, the biopsy Gleason score, the American Society of Anesthesiologists classification score, and prostate volume assessed during transrectal ultrasonography. All RRP and RALP procedures were performed by experienced surgeons. RESULTS: Mean time to prostatectomy was 67.4 months in the RALP group and 53.1 months in the RRP group. Mean operative time was 217 ± 51.9 minutes for RALP and 174 ± 57.7 minutes for RRP (P<0.05). The overall positive surgical margin rate was 15.8% in both groups (pT(2) tumors: 10.5% for RALP and 5.3% for RRP; P=1.0). Mean estimated blood loss was 333 ± 144 mL in RALP patients and 1103 ± 636 mL in RRP patients (P<0.001). The difference between preoperative and postoperative hemoglobin levels was 3.22 ± 0.98 g/dL for RALP and 5.85 ± 1.95 g/dL for RRP (P=0.0002). The RALP and RRP groups also differed in terms of hospital stay (8.58 ± 1.17 vs 11.74 ± 5.22 days; P=0.0037), duration of catheterization (7.95 ± 5.69 vs 11.78 ± 6.97 days; P=0.0016), postoperative complications according to the Clavien classification system (6 vs 15 patients; P=0.0027), and transfusion rate (0% vs 10.5%; P<0.001). CONCLUSION: RALP offers advantages over open radical prostatectomy after previous surgery. Although both techniques are associated with adequate surgical outcomes, RALP appeared to be preferable in our population of patients with previous prostate surgery.

Neuroendocrine tumor cells in prostate cancer: evaluation of the neurosecretory products serotonin, bombesin, and gastrin - impact on angiogenesis and clinical follow-up.

BACKGROUND: Neuroendocrine differentiated tumor cells (NETC) can be found in a large portion of prostate carcinoma (PCa) specimens. This is the first study to systematically quantify and analyze the influence of the NETC distribution and of their secretory products, serotonin, bombesin, and gastrin, on angiogenesis and in the clinical follow-up of PCa patients. METHODS: 175 PCa specimens were included in this study. NETC were displayed using the marker CgA. Specimens showing a high expression of CgA were analyzed for serotonin, bombesin, and gastrin. Blood vessels were stained with the epitope CD34. Data was analyzed for inter-correlation and its correlation to clinical-pathological parameters and the results of a mid-term follow-up. RESULTS: The number of NETC was correlated with the pT-status and the Gleason score. Specimens with high NETC expression had an increased microvessel density (MVD). No correlation between the neurosecretory products and the clinical-pathological parameters was found. High NETC expression, high bombesin expression and increased MVD were associated with early treatment failure in the follow-up. CONCLUSION: NETC have an influence on angiogenesis and are correlated with the clinical-pathological parameters. A high expression of NETC is associated with an early failure of treatment. Our study underlines the importance of NETC in prostate cancer.

Gastrin-releasing peptide: predictor of castration-resistant prostate cancer?

BACKGROUND: Neuroendocrine (NE) cells of the prostate are known to be androgen-independent and NE peptides like gastrin-releasing peptide (GRP) or neuron-specific enolase (NSE) can stimulate growth in a paracrine manner, and this is thought to be one of the escape mechanisms in castration-resistant prostate cancer (CRPCa). In a longitudinal study, we investigated the development of the NE serum factors GRP, NSE, and chromogranin A and their correlation with prostate-specific androgen (PSA) during hormonal treatment. MATERIALS AND METHODS: Thirty two patients, with histology-proven, localized or metastatic prostatic carcinoma (PCa), who were undergoing therapy with LHRH analogue or a combination of LHRH analog and peripheral androgen blockade, took part in the study. In addition, eight healthy volunteers were each tested twice for serum GRP to elicit a "physiological" standard value. Blood samples were taken periodically from each patient within an 18-month time frame. RESULTS: We defined the standard value for GRP in the healthy participants as 0.852 ng/ml (mean + 2 SD) and observed that the GRP values for patients with PCa were significantly higher (P = 0.034). There was a positive correlation between PSA and GRP in patients with biochemical failure. CgA correlated with PSA development in the CRPCa patients. NSE values rose steadily over the study period, but with no correlation to PSA. CONCLUSION: Our data confirm that NE factors are elevated during hormonal treatment of prostate cancer. GRP is higher in PCa patients undergoing androgen deprivation therapy and is possibly involved in the initiation of hormonal escape in PCa.

Clinical impact of intraoperative frozen sections during nerve-sparing radical prostatectomy.

PURPOSE: Enhanced surgical techniques and standardised selection criteria have led to a higher rate of nerve-sparing (NS) radical prostatectomy (RP) procedures. The aim of this study was to evaluate the clinical value of intraoperative frozen sections (IFS) during nerve-sparing radical prostatectomy (NSRP). MATERIALS AND METHODS: Thousand and eighty-three patients with localised prostatic carcinoma were treated using retropubic RP (from 2004 to 2006). Two hundred and eighty-seven of the 1083 documented cases received NS. One hundred and thirty procedures were carried out with IFS from the area of the neurovascular bundles and 157 without IFS. The decision to use IFS was made intraoperatively and based on clinical suspicion of possible positive resection margins in the area of the bundles. RESULTS: In the NS group with IFS, the results revealed positive margins in nine (6.9%) out of 130 cases, resulting in subsequent resection of the ipsilateral neurovascular bundle. The final histological report on this group revealed four additional patients (3.1%) with positive margins, but only one (0.7%) in the area of the previous neurovascular bundle. The final histopathologic reports on the 157 NS cases without IFS showed that the positive margin was in the area of the previous neurovascular bundle in only one (0.6%) of the nine cases with positive margins (5.7%). CONCLUSION: According to our data, there is no need for routine IFS during NSRP. The negative predictive value for infiltration of the NVB is high, and IFS can be dispensed with. Intraoperative biopsies should be taken in those cases where the surgeon is in doubt about the resection margins in the area of bundles.

120 W lithium triborate laser for photoselective vaporization of the prostate: comparison with 80 W potassium-titanyl-phosphate laser in an ex-vivo model.

PURPOSE: To evaluate the ablative and hemostatic properties of the recently introduced 120 W lithium triborate (LBO) 532 nm laser and compare the results against the conventional 80 W potassium-titanyl-phosphate (KTP) laser. MATERIALS AND METHODS: The ex-vivo model of the isolated blood-perfused porcine kidney was used to determine the ablation capacity, hemostatic properties, and coagulation depth of the GreenLight HPS laser system (American Medical System, Minnetonka, MN) that used an output power of 120 W. The results were compared with the KTP laser that used output power levels of 30 W, 50 W, and 80 W. Unperfused kidneys were weighed before and after 10 minutes of laser ablation in an area of 3 x 3 cm; the weight difference marked the amount of removed tissue. Bleeding was determined by the weight difference of a swab before and after it was placed on the bleeding surface for 60 seconds after ablating a surface area of 9 cm(2) on blood-perfused kidneys. RESULTS: With a tissue removal of 7.01 +/- 1.83 g after 10 minutes of laser ablation at 120 W, the LBO laser offered a significantly higher ablation capacity compared with 3.99 +/- 0.48 g reached with the conventional KTP laser at 80 W in the same time interval (P < 0.05). The bleeding rate was also significantly increased using the LBO at 120 W compared with the conventional device at 80 W (0.65 +/- 0.26 g/min vs 0.21 +/- 0.07 g/min; P < 0.05). The corresponding depths of the coagulation zones were 835 +/- 73 microm and 667 +/- 64 microm (P < 0.05), respectively. CONCLUSION: The 120 W LBO laser offers a significantly higher tissue ablation capacity compared with the conventional 80 W KTP laser. Because the increased efficacy of the device is accompanied by a higher bleeding rate and a slightly deeper coagulation zone, the user has to select the appropriate output power levels carefully for a safe and efficient treatment. Nevertheless, the bleeding rate compared with previous studies of transurethral resection of the prostate is significantly reduced.

Dose-dependent growth inhibition in vivo of PC-3 prostate cancer with a reduction in tumoral growth factors after therapy with GHRH antagonist MZ-J-7-138.

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various cancers and affect tumoral growth factors. METHODS: We investigated the effect of a new GHRH antagonist MZ-J-7-138 at doses of 1.25, 2.5, 5 and 10 microg/day s.c. on the growth of PC-3 human androgen independent prostate cancers xenografted s.c. into nude mice. Binding assays were used to investigate GHRH receptors. The levels of IGF-II and VEGF in tumors were measured by radioimmunoassays. RESULTS: Treatment with 2.5, 5, and 10 microg/day MZ-J-7-138 caused a significant dose-dependent growth reduction of PC-3 tumors. The greatest inhibition of 78% was obtained with 10 microg/day. The suppression of IGF-II protein levels in tumors was seen at all doses of MZ-J-7-138, but only 10 microg dose induced a significant inhibition. MZ-J-7-138 also reduced VEGF protein levels, the inhibition being significant at doses of 5 and 10 microg. Specific high affinity binding sites for GHRH were found on PC-3 tumors using (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-138 displaced radiolabeled JV-1-42 with an IC(50) of 0.32 nM indicating its high affinity to GHRH receptors. Real-time PCR analyses detected splice variant 1 (SV1) of GHRH receptor (GHRH-R) as well as pituitary type of GHRH-R and GHRH ligand. CONCLUSION: Our results demonstrate the efficacy of GHRH antagonist MZ-J-7-138 in suppressing growth of PC-3 prostate cancer at doses lower than previous antagonists. The reduction of levels of growth factors such as VEGF and IGF-II in tumors by GHRH antagonist was correlated with the suppression of tumor growth.