Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5.

PURPOSE: Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown. METHODS: In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components. RESULTS: FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p < 0.001 in TCGA and MSKCC). Correlation with TCGA subtypes revealed FABP5 overexpression to be associated with SPOP and FOXA1 mutations. FABP5 was positively correlated with potential drug targets located downstream of FABP5 in the PPAR-signaling pathway. CONCLUSION: FABP5 overexpression is frequent in PCa, but seems to be restricted to TMPRESS2:ERG fusion-negative tumors and is associated with SPOP and FOXA1 mutations. FABP5 overexpression appears to be indicative for increased activity in PPAR signaling, which is potentially druggable.

[S2e guideline of the German urologists: Conservative and pharmacologic treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Konservative und medikamentöse Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the conservative and pharmacological treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding watchful waiting, behavioral therapy, phytotherapy and pharmacological mono- and combination therapy. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

[S2e guideline of the German urologists: Instrumental treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Instrumentelle Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the instrumental treatment of the lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding open and transurethral procedures (TUR-P, bipolar TUR-P, TUI-P, HE-TUMT, TUNA, and the different Laser techniques). Recommendations are also given concerning intraprostatic stents and injection therapies. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

Transurethral resection of the prostate: defending its leading position in the management of benign prostatic enlargement.

UNLABELLED: Although challenged by medical therapy and numerous minimal-invasive treatment modalities, transurethral resection of the prostate (TURP) is still considered as the gold standard of interventional treatment of benign prostatic enlargement (BPE). It is characterized by an immediate improvement in symptoms and voiding parameters and achieves long lasting RESULTS: While its efficacy is out of question, the associated peri- and postoperative morbidity remains a major point of criticism and has let to the introduction of numerous less invasive treatment options. On the other hand, this also brought various improvements in the technique of TURP aiming to improve treatment results and reduce perioperative morbidity. This review article gives an overview over the historical development, treatment results, associated complications and recent technical developments in TURP, highlighting especially the role of bipolar TURP.

[Medical treatment of metastatic renal cell carcinoma after the approval and market entry of multitargeted tyrosine kinase inhibitors in Germany]. / Medikamentöse Therapie des metastasierten Nierenzellkarzinoms: eine Standortbestimmung nach Einführung der Multi-Tyrosinkinaseinhibitoren in Deutschland.

PURPOSE: To describe the current use and administration of multitargeted tyrosine kinase inhibitors (sunitinib and sorafenib) in the management of metastatic renal cell carcinoma (RCC) and to characterise frequent adverse events. MATERIALS AND METHODS: A questionnaire was sent to 104 urologists and medical oncologists having their own practice. The common use of medical treatment with sunitinib and sorafenib in patients with metastatic RCC was recorded. Data on the most frequent drug-associated adverse events were registered and described in a preliminary patient cohort. RESULTS: Medical oncologists in private practice treat over twice as many patients with metastatic RCC (8/year) as established urologists. Most medical oncologists but not urologists already use multitargeted tyrosine kinase inhibitors. For the initiation of treatment, most urologists admit patients to a hospital, whereas medical oncologists start and carry out medical treatment themselves. In all patients adverse events occurred due to medical treatment, leading to therapy stop or pause in 53% of patients. The most frequent adverse events were abnormal fatigue, arterial hypertension, diarrhoea and the hand-foot skin syndrome. CONCLUSIONS: Multitargeted tyrosine kinase inhibitor therapy in Germany is currently done predominantly by medical oncologists rather than urologists. Adverse events caused by sunitinib and sorafenib frequently required medical care, and in our initial series of patients prompted physicians to pause treatment.

[Complications and side effects of low dose rate brachytherapy for the treatment of prostate cancer: data on a 13 year follow-up study from Mannheim]. / Komplikationen und Nebenwirkungen der LDR-Brachytherapie beim Prostatakarzinom : 13-Jahresdaten aus Mannheim.

BACKGROUND: Brachytherapy (BT) is an established treatment option for low risk prostate cancer. The aim of this study was to determine the long-term complications and side effects of the procedure in an up to 13 year long single center follow-up analysis. MATERIAL: A total of 505 patients were treated by BT for prostate cancer between May 1991 and August 2005. Cohort I (n=412; May 1991 to November 2003) was evaluated by written questionnaire (modified ICS male) and patient chart evaluation in terms of side effects and secondary interventions. In cohort II (n=148; January 2002 to August 2005) perioperative complications were investigated. RESULTS: The mean follow-up was 5.5 years. Perioperative complications were present in 5.4% of patients. Transurethral resection of the prostate was a common secondary intervention, performed in 7% of cases. The rate of incontinence was 6.3% in the long-term follow-up, the rate of potency was 43.5% in those patients who were potent before BT and no hormonal manipulation was performed at any time. CONCLUSION: BT is a minimally invasive procedure for the treatment of localised "low risk" prostate cancer. Perioperative complications are rare, secondary intervention may be necessary and the patient has to be informed of possible impotence, incontinence and lack of ejaculation.

[Further development of urology in the tension field of surgical and molecular medicine]. / Weiterentwicklung der Urologie im Spannungsfeld von operativer und molekularer Medizin.

Methods based on molecular biology and molecular medicine now have important practical applications in many areas of theoretical and clinical medicine, and it is no longer possible to imagine life without them. This means that in a largely surgical discipline, such as urology, completely new challenges are coming to the fore, which urology, as an academic and clinical discipline, now has to face up to, and to a much greater degree than hitherto. However, there is less and less freedom of action in any university department of urology, as a result not only of intensified legal outline conditions in the healthcare sector and tight public budgets, but also of faculty- and hospital-specific blocks to innovation. There is an urgent need for the creation of appropriate outline conditions and innovative structures that will allow efficient surgical care and also an efficient way of working scientifically.

[Long-term follow-up of interstitial laser coagulation in the treatment of benign prostatic hyperplasia]. / Langzeitergebnisse der interstitiellen Laserkoagulation zur Behandlung der benignen Prostatahyperplasie.

INTRODUCTION: Besides standard open or transurethreal adenoma resection, less morbid interstitial laser coagulation (ILC) is an alternative therapeutical option that could reduce lower urinary tract symptoms, especially in high-risk patients. Although short-term results indicate effectiveness, reliable long-term statistics are still lacking. Therefore, to assess long-term satisfaction and overall success rate, we re-evaluated patients with a mean follow-up of 7 years after laser treatment. METHODS: A total of 72 patients had been included in our ILC programme between 1993 and 1995. Mean age was 74 years. About 45 % of the patients had since died of other causes. In all, 23 patients were evaluated by telephone questionnaire, International Prostate Symptom Score (IPSS), Quality of Life (QoL), second surgical interventions or medical therapy. Our patient group was treated with interstitial Nd:YAG laser coagulation (mediLas fibertom). A perineal (34 %), transurethral (23 %) or combined (43 %) approach was chosen, depending on the preoperative volume of the prostate (range 40 - 100 ml; mean 59.3 ml). RESULTS: 68.4 % of the patients were satisfied with their current urological situation. Mean IPSS was 8.8 vs. 18.8 preoperatively mean QoL 1.5 vs. 3.3. 15.8 % had undergone conventional transurethral prostatic resection in the interim; one patient uses a urine catheter. 15.8 % receive medical treatment for lower urinary tract symptoms. CONCLUSIONS: Although the results of standard TUR or open surgery imply higher success, the long-term results of ILC demonstrate effectiveness. Further follow-up studies on a larger number of patients are advisable. The low morbidity of ILC makes this procedure an interesting alternative option in the treatment of high risk patients.

[Established and new urological therapeutic options in the management of prostate carcinoma]. / Bewährte und neue urologische Therapien des Prostatakarzinoms.

The surgical and medical management of carcinoma of the prostate is a central issue in urology. Radical prostatectomy is the standard procedure in the curative therapy of locally confined carcinoma of the prostate. Recently, alternative minimally invasive options such as brachytherapy and the still experimental focused ultrasound and cryotherapy have gained in interest. Further palliative schemes such as hormonal ablation and chemotherapy have become established in the management of locally advanced and generalized carcinoma or elderly patients. It was our objective to give an account of these established and new urological therapy options in the management of carcinoma of the prostate.

Rotoresect for bloodless transurethral resection of the prostate: a 4-year follow-up.

OBJECTIVE: To report the results and long-term follow-up of transurethral resection of the prostate (TURP) with a new resection device, the Rotoresect (Karl Storz, Tuttlingen, Germany). PATIENTS AND METHODS: Most endoscopic resection techniques for benign prostatic tissue aim for high ablation rates and minimal bleeding. Available resection electrodes are effective, but cause high blood loss (loop electrode), or less bleeding but poorer ablation rates (electrovaporization). To resolve these conflicts the Rotoresect was developed in 1995; it consists of a specially designed rotating resection electrode, driven by a micromotor, and a high-frequency current to enable simultaneous coagulation, vaporization and mechanical tissue removal during resection. To date, 84 patients with benign prostatic hyperplasia have had their prostate resected with this device (mean prostate size 46.0, sd 18.4 mL) and have been assessed for up to 4 years. RESULTS: During resection there was very little bleeding, with no significant changes in haemoglobin or sodium levels. The mean (sd) duration of catheterization was 1.4 (1.1) days; the urinary peak flow rate was improved from 9.7 (3.2) to 24.2 (8.23) mL/s and the residual urine volume reduced from 187.3 (109.6) to 22.7 (19.5) mL. The International Prostate Symptom Score and quality-of-life index were both improved, from 24.0 (7.5) to 4.1 (2.7), and 4.2 (3.2) to 0.8 (0.9), respectively. Overall the results were stable during the 4 years of follow-up. CONCLUSION: The Rotoresect combines the advantages of standard resection (high ablation rate) by actively rotating the resection electrode, and the haemostatic effect of electrovaporization (minimal blood loss) by simultaneous tissue coagulation and vaporization.

Durability of laser probes in interstitial thermotherapy: investigations on an ex vivo model of effect of carbonization.

BACKGROUND AND PURPOSE: Interstitial laser application is successful for clinical tissue ablation in various organs. One great drawback of this method is the high costs caused by the vulnerability of the probes. Our objective was to investigate whether the prevention of carbonization deposits on laser probes averts reduced transmission after the application of high laser energy. MATERIALS AND METHODS: Interstitial laser probes were used to pierce an in vitro kidney model, and 9900 J of energy (Nd:YAG laser) was applied. The transmission of the laser probe was determined and compared with that of a reference probe. RESULTS: The application of laser energy, up to a total of 49,500 J, did not reduce transmission. The deviation of the transmission comparing working probes and the reference probe was between 2% and 7%. The application of high energy (40 W) over a longer period (>20 seconds) led to carbonization and consequent distinct reduction of transmission. CONCLUSIONS: The durability of laser probes can be prolonged by preventing carbonization. The economic effect achieved is the repeated use of the probes at less expense.

Clinical evaluation of a newly developed endoscopic resection device (Rotoresect): physical principle and first clinical results.

BACKGROUND: Endoscopic resection techniques on benign prostatic tissue aim at a high ablation rate and a minimal bleeding rate. Although commercial resection electrodes are effective, they either cause high blood loss (loop electrode) or reduce the bleeding rate with a compromised ablation rate (electrovaporization electrode). To resolve these problems, a new electrosurgical resection device, The Rotoresect, has been developed. METHODS: The Rotoresect incorporates a specially designed working element. The resection electrode is driven by a micromotor with a high-frequency current that enables simultaneous coagulation and vaporization during rotoresection. To date, 40 patients with benign prostatic hyperplasia have undergone transurethral rotoresection of the prostate with this new device. RESULTS: The actively rotating resection electrode enables tissue coagulation and vaporization as well as mechanical tissue ablation. Only slight bleeding was observed during the entire resection procedure. Postoperatively, no significant changes in hemoglobin and sodium concentration were detected. The deobstructive effect of the Rotoresect was comparable to that of the standard loop. CONCLUSIONS: The simultaneous tissue vaporization, coagulation, and mechanical removal by the Rotoresect enables a high ablation rate combined with minimal blood loss. Initial clinical results gained in the transurethral resection of benign prostatic tissue are promising.