Florian Imkamp

Oncological and functional results of open, robot-assisted and laparoscopic radical prostatectomy: does surgical approach and surgical experience matter?

The treatment of prostate cancer has undergone a fundamental change in the last decade. New surgical and nonsurgical minimal invasive methods have evolved. As the methodology of the different treatments is commonly known to urologists, this article focuses on oncological and functional outcome of open retropubic (ORP), trans- or extraperitoneal endoscopical (LRP), and robot-assisted radical prostatectomy (RALP), based on personal experience and review of the literature. A MEDLINE search was performed to review the literature on LRP and RALP between 1982 and 2007 with special emphasis on oncological and functional results, technical considerations, comparison of LRP and RALP to ORP, laparoscopic training, historical aspects, and cost-efficiency of the techniques. Based on diligent training and proctoring programs, a continuous dissemination of laparoscopic techniques takes place. There is a trend towards the extraperitoneal access in most of the minimal invasive programs at least in the European community. Mid-term outcomes of LRP and short-term outcomes of RALP achieved equivalence to open surgery with regards to complications, oncologic and functional results. Distinct advantages of LRP include less postoperative pain, lower transfusion rates, shorter convalescence, and better cosmetics. In contrast to RALP, LRP reaches cost-equivalence with open surgery in selected centers. LRP and RALP reproduce the short-term results of open surgery while providing the advantages of a minimal access. Video-assisted teaching improves the transfer of anatomical knowledge and technical knowhow, but the discussion about the longer learning curve for laparoscopy handling remains. The future will show if European centers adopt the use of robots comparable to the United States.

Current evidence for transurethral laser therapy of non-muscle invasive bladder cancer

IntroductionBladder cancer is the second most common malignancy of urologic tumors. Back in 1976, lasers were added to the endourological armetarium for bladder tumor treatment. Despite nowadays’ standard procedure for staging and treating non-muscle invasive bladder tumor by transurethral resection of bladder tumors (TURB) via a wire loop, laser resection techniques for bladder tumor came back in focus with the introduction of Ho:YAG and not to mention recently Tm:YAG lasers. This review aims to display the current evidence for these techniques.Materials and methodsThroughout April 2010, MEDLINE and the Cochrane central register of controlled trials were searched previously for the following terms: “Laser, resection, ablation, coagulation, Nd:YAG Neodym, HoYAG: Holmium, Tm:YAG Thulium and transitional carcinoma, bladder, intravesical.”ResultsEleven articles on Ho:YAG and 7 on Tm:YAG were identified. Searches by Cochrane online library resulted in no available manuscripts.ConclusionToday, Nd:YAG does not play any role in treatment of lower urinary tract transitional cell carcinoma. Ho:YAG and Tm:YAG seem to offer alternatives in the treatment of bladder cancer, but still to prove their potential in larger prospective randomized controlled studies with long-term follow-up. Future expectations will show whether en bloc resection of tumors are preferable to the traditional “incise and scatter” resection technique, in which is contrary to all oncological surgical principles. For the primary targets, here are within first-time clearance of disease, in addition to low in-fields and out-of-fields recurrence rates.

Prospective Randomized Evaluation of Risk-adapted Prostate-specific Antigen Screening in Young Men: The PROBASE Trial

Department of Urology, University Hospital, Heinrich-Heine-University, Dusseldorf, Germany; Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, Heidelberg, Germany; Department of Urology, University Hospital, Ruprecht-Karls-University, Heidelberg, Germany; Department of Urology, University Hospital, Technical University of Munich, Munich, Germany; Department of Urology, University Hospital, Hannover Medical School, Hannover, Germany; University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf, Germany; Department of Pathology, University Hospital, Rheinische Friedrich-Wilhelms-University, Bonn, Germany; Department of Urology, University Hospital, Rheinische Friedrich-Wilhelms-University, Bonn, Germany; Department of Urology, University Hospital, Westfalische Wilhelms-University, Munster, Germany; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Department of Laboratory Medicine, Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA; Department of Urology, Erasmus Medical Center Rotterdam, The Netherlands

Apoptosis gene polymorphisms and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy

BACKGROUND AND OBJECTIVES Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis. METHODS AND MATERIALS Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms. RESULTS SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02). CONCLUSIONS These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.

Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue

INTRODUCTION Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI alpha and beta isoforms has not been evaluated in human penile erectile tissue. AIM To evaluate the expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). METHODS Cryostat sections of HCA and HCC were incubated with primary antibodies directed against alpha-actin, cGMP, eNOS, cGKI, cGKI alpha, and cGKI beta. Visualization of double-labeled immunofluorescent stainings was achieved by laser microscopy. Western blot analysis was performed in order to confirm the expression of cGKI isoforms. MAIN OUTCOME MEASURES Expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and eNOS in human penile erectile tissue. RESULTS Immunoreactivities specific for cGKI, cGKI alpha, and cGKI beta were observed within the smooth musculature and the endothelium of cavernous arteries and sinusoids. Double stainings revealed the colocalization of alpha-actin, cGMP, eNOS, and cGKI isoforms. The expression of cGKI isoforms was confirmed by Western blot analysis. CONCLUSIONS Our results demonstrate, for the first time, the expression of both cGKI alpha and beta isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI alpha and beta provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

Insertion Sheaths Prevent Breakage of Flexible Ureteroscopes Due to Laser Fiber Passage: A Video-Endoluminal Study of the Working Channel

BACKGROUND It has been postulated that laser insertion sheaths prevent mechanical damage to the inside of working channels of flexible ureteroscopes. The presented study, for the first time, aims at confirming this hypothesis and visualized the damage of the endoscopic working channel by video-endoluminal observation after a series of laser fiber passages with or without the protection of a laser fiber insertion sheath. MATERIALS AND METHODS Four nonassembled working channels of two different manufacturers (Olympus™, Wolf™) were tested in a deflection model (50° and 180°). Flexifib™ laser fibers (LISA laser products) with an optical core diameter of 273 μm were inserted through 0.9% NaCl irrigated working channels in cycles of 10 insertions either with or without protection of the Flexgard™ insertion sheath. After 30 insertions, the examination cycle was reduced to 5 insertions each cycle until breakage. Test cycles were followed by endoluminal video examination of the working channel with the 2.4F flexible fiber scope by Polydiagnost™. Damage to the working channel was classified as streaks with superficial stress marks of the surface, scratches with embossed margins, or perforations. RESULTS No scratching or perforation occurred in the insertion sheath group in up to 150 insertions in all working channels and both deflection grades. In the group without insertion sheaths, scratches were visible after 40 to 50 insertions with 50° deflection and 30 insertions with 180° deflection. Perforations of the working channels were seen after 95 insertions with 50° and 60 insertions with 180° deflection. CONCLUSIONS Severe damage to working channels depends on the degree of deflection and may occur after 30 insertions only. Relevant damage to the working channel may be avoided by using a laser fiber insertion sheath.

Acceptance, Prevalence and Indications for Robot-Assisted Laparoscopy - Results of a Survey Among Urologists in Germany, Austria and Switzerland.

Background: Robotic-assisted laparoscopy (RAL) is being widely accepted in the field of urology as a replacement for conventional laparoscopy (CL). Nevertheless, the process of its integration in clinical routines has been rather spontaneous. Objective: To determine the prevalence of robotic systems (RS) in urological clinics in Germany, Austria and Switzerland, the acceptance of RAL among urologists as a replacement for CL and its current use for 25 different urological indications. Materials and Methods: To elucidate the practice patterns of RAL, a survey at hospitals in Germany, Austria and Switzerland was conducted. All surgically active urology departments in Germany (303), Austria (37) and Switzerland (84) received a questionnaire with questions related to the one-year period prior to the survey. Results: The response rate was 63%. Among the participants, 43% were universities, 45% were tertiary care centres, and 8% were secondary care hospitals. A total of 60 RS (Germany 35, Austria 8, Switzerland 17) were available, and the majority (68%) were operated under public ownership. The perception of RAL and the anticipated superiority of RAL significantly differed between robotic and non-robotic surgeons. For only two urologic indications were more than 50% of the procedures performed using RAL: pyeloplasty (58%) and transperitoneal radical prostatectomy (75%). On average, 35% of robotic surgeons and only 14% of non-robotic surgeons anticipated RAL superiority in some of the 25 indications. Conclusions: This survey provides a detailed insight into RAL implementation in Germany, Austria and Switzerland. RAL is currently limited to a few urological indications with a small number of high-volume robotic centres. These results might suggest that a saturation of clinics using RS has been achieved but that the existing robotic capacities are being utilized ineffectively. The possible reasons for this finding are discussed, and certain strategies to solve these problems are offered.

Role of free testosterone levels in patients with metastatic castration-resistant prostate cancer receiving second-line therapy

A range of new treatment options has recently become available for patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone is continued when performing chemotherapy or androgen deprivation with new second-generation therapeutic agents such as enzalutamide or abiraterone acetate. Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only. The aim of the present study was to evaluate the role of FT as a prognostic biomarker for cancer-specific survival (CSS) and its feasibility as an ADT monitoring biomarker in patients with mCRPC for the first time. The requirement for continued ADT in mCRPC patients is discussed within the basis of the current literature. A total of 34 patients with continuous measurements of FT levels and mCRPC status underwent therapy with docetaxel, abiraterone acetate, enzalutamide, cabozantinib, carboplatin or cabazitaxel. Data were obtained from the Departments of Urology and Urological Oncology, Hannover Medical School (Hannover, Germany) between March 2009 and April 2014. A cutoff point of 0.5 pg/ml was used to discriminate between patients according to FT levels. Statistical evaluation of CSS was performed by applying Kaplan Meier survival estimates, multivariate Cox regression analyses and log-rank tests. The median age of all 34 patients was 72 years (range, 51–86 years). The mean follow-up interval was 16.1 months (range, 0.7–55.6 months). Despite the fact that all patients were undergoing androgen deprivation, the mean serum FT levels for each patient varied; the mean FT concentration in the cohort was 0.328 pg/ml, ranging from 0.01–9.1 pg/ml. A notable difference with regard to CSS was observed for patients with regard to serum FT concentration; CSS was significantly longer for patients with a serum FT level below the cutoff level (43.6 vs. 17.3 months, respectively, P=0.0063). Upon multivariate Cox regression analysis, the mean FT concentration during treatment remained a significant prognostic factor for CSS (hazard ratio, 1.22; 95% confidence interval, 1.03–1.43; P=0.0182). In conclusion, in patients with mCRPC, the serum FT level is a strong predictor of CSS in patients under therapy with second-line anti-hormonal therapeutic medication and chemotherapy. It may be concluded that FT levels should be included into the routine control of androgen suppression while under treatment with ADT and second-generation hormonal therapy.

Minimally invasive approaches to adrenal tumors: an up-to-date summary including patient position and port placement of laparoscopic, retroperitoneoscopic, robot-assisted, and single-site adrenalectomy.

Purpose of review There are multiple minimal invasive approaches to remove the adrenal gland. The purpose of this review is to summarize the most up-to-date findings about laparoscopic, retroperitoneoscopic, robot-assisted, and single-site adrenalectomy, and to define the most common approaches to the adrenal gland. Recent findings Laparoscopic adrenalectomy is the gold standard to remove adrenal tumors. New approaches are being explored to outperform the advantages of laparoscopic adrenalectomy. Summary Retroperitoneoscopic adrenalectomy, when performed by skilled surgeons, offers an alternative to the conventional laparoscopic approach, with better outcome. The robot-assisted and single-site approaches still need further studies to fully identify their roles in adrenalectomy.

Neoadjuvant Chemotherapy Using Reduced-Dose Docetaxel Followed by Radical Prostatectomy for Patients With Intermediate and High-Risk Prostate Cancer: A Single-Center Study

To assess safety, pathologic response rate, and long‐term oncologic outcomes of radical prostatectomy (RP) after neoadjuvant chemotherapy using reduced‐dose docetaxel without androgen‐deprivation therapy in prostate cancer (PCa) patients of intermediate‐ and high‐risk groups.