Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation.

The canonical Wnt signaling pathway is of paramount importance in development and disease. An emergent question is whether the upstream cascade of the canonical Wnt pathway has physiologically relevant roles beyond ß-catenin-mediated transcription, which is difficult to study due to the pervasive role of this protein. Here, we show that transcriptionally silent spermatozoa respond to Wnt signals released from the epididymis and that mice mutant for the Wnt regulator Cyclin Y-like 1 are male sterile due to immotile and malformed spermatozoa. Post-transcriptional Wnt signaling impacts spermatozoa through GSK3 by (1) reducing global protein poly-ubiquitination to maintain protein homeostasis; (2) inhibiting septin 4 phosphorylation to establish a membrane diffusion barrier in the sperm tail; and (3) inhibiting protein phosphatase 1 to initiate sperm motility. The results indicate that Wnt signaling orchestrates a rich post-transcriptional sperm maturation program and invite revisiting transcription-independent Wnt signaling in somatic cells as well.

CD15 is a risk predictor and a novel target in clear cell renal cell carcinoma.

INTRODUCTION: Tumor cells use adhesion molecules like CD15 or sialylCD15 (sCD15) for metastatic spreading. We analyzed the expression of CD15 and sCD15 in clear cell renal cell carcinoma (ccRCC) regarding prognosis. METHODS: A tissue microarray containing tissue specimens of 763 patients with ccRCC was immunohistochemically stained for CD15 and sCD15, their expression quantified using digital image analysis and the impact on patients' survival analyzed. The cell lines 769p and 786o were stimulated with CD15 or control antibody in vitro and the effects on pathways activating AP-1 and tumor cell migration examined. RESULTS: ccRCC showed a broad range of CD15 and sCD15 expression. A high CD15 expression was significantly associated with favorable outcome (p<0.01) and low-grade tumor differentiation (p<0.001), whereas sCD15 had no significant prognostic value. Tumors with synchronous distant metastasis had a significantly lower CD15 expression compared to tumors without any (p<0.001) or with metachronous metastasis (p<0.01). Tumor cell migration was significantly reduced after CD15 stimulation in vitro, but there were no major effects on activating pathways of AP-1. CONCLUSION: CD15, but not sCD15, qualifies as a biomarker for risk stratification and as an interesting novel target in ccRCC. Moreover, the data indicates a contribution of CD15 to metachronous metastasis. Further research is warranted to decipher the intracellular pathways of CD15 signaling in ccRCC in order to characterize the CD15 effects on ccRCC more precisely.

Cavoatrial hypernephroma resection on cardiopulmonary bypass: Mild/normo-versus moderate hypothermia.

INTRODUCION: Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors. It extends up into the systemic veins and right atrium. Surgical extraction of such extensions is usually carried out using cardiopulmonary bypass (CPB) with moderate hypothermic (MH) being frequently applied in order to obtain a clear surgical field. However, due to obvious disadvantages of hypothermia, approaches with mild/normothermia (NT) during CPB have also been established. The current study aims to compare the outcomes of patients undergoing RCC tumor and extensions resection using MH versus NT. MATERIAL AND METHODS: This is a retrospective, non-randomized study. All patients who underwent RCC tumor and extensions resection for stage III or IV (Staehler) RCC in a single center between 2006 and 2020 were included. During surgery, MH or NT were applied. CPB was realized using aortic and bicaval cannulation. We compared the procedural times, transfusion requirements and postoperative outcomes, respectively between the MH and NT groups. RESULTS: A total of 24 consecutive patients (n(NT) = 12, n(MH) = 12) were included in the study (median age NT 68.5 and MH 66.5). The study only showed a significant difference in heart-lung machine times (median CPB time NT 45.5 min and MH 110.0 min, p = 0.004). All other results, loss of drainage, administration of blood products, as well as the postoperative course and mortality were comparable in both groups. CONCLUSION: The results showed a high perioperative and long-term mortality. The perioperative course was similar after surgery with NT or MH. Therefore, NT which minimizes potential complications of MH should be preferred.

Salvage Radiotherapy for Recurrent Prostate Cancer after High-Intensity Focused Ultrasound Therapy: Quality of Life and Functional Outcome.

INTRODUCTION: The aim of this study was to evaluate toxicity, oncological and functional outcome, and quality of life after salvage radiotherapy for recurrent prostate cancer after high-intensity focused ultrasound (HIFU) therapy. METHODS: A total of 13 patients undergoing salvage radiotherapy for biopsy-proven prostate cancer recurrence after HIFU therapy were included and followed up every 3 months. Oncological outcome (by PSA measurements), toxicity (according to CTCAE criteria), and functional outcome were evaluated. Quality of life was assessed by standardized questionnaires (QLQ-C30 and QLQ-PR25) at baseline, 3 months, and 12 months after salvage treatment. RESULTS: Median age of patients was 80 years (interquartile range [IQR] 75-82). Patients underwent normofractionated salvage radiotherapy with median 73.6 Gy. PSA nadir was reached at 6 months and was 0.2 ng/mL. Median follow-up was 76 months (IQR 55-96). Biochemical recurrence occurred in 3 patients (23.1%) at a median of 36.4 months. No gastrointestinal (GI) or genitourinary (GU) toxicity ≥ grade 3 was noted during follow-up. Early and late grade II GI toxicity occurred in 1 patient (7.7%), respectively. GU toxicity grade II was noted in up to 53.8% at 3 months and 61.5% at 12 months. In terms of health-related quality of life, there was no statistically significant difference at 3 and 12 months compared to the baseline. Only differences were seen in sexual functioning (3 and 12 months) and in diarrhea (3 months), affecting patients' wellbeing. DISCUSSION/CONCLUSION: Salvage radiotherapy after HIFU treatment can be performed safely, thereby providing acceptable recurrence-free survival without severe impact on post-interventional quality of life.

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer.

PURPOSE: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). MATERIALS AND METHODS: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. RESULTS: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05). CONCLUSIONS: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease.

Magnetic resonance imaging-guided transurethral ultrasound ablation in patients with localised prostate cancer: 3-year outcomes of a prospective Phase I study.

OBJECTIVES: To report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. PATIENTS AND METHODS: As a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3 years. RESULTS: A 3-year follow-up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1-0.4) ng/mL, stable to 0.8 (0.4-1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. CONCLUSION: With 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

Recovery of pad-free continence in elderly men does not differ from younger men undergoing robot-assisted radical prostatectomy for aggressive prostate cancer.

PURPOSE: To analyze urinary continence outcome following robot-assisted radical prostatectomy (RARP) for aggressive prostate cancer in men aged ≥ 70 and < 70 years. METHODS: Retrospective analyses of prospectively collected long-term data from a monocentric cohort of 350 men with D'Amico high-risk prostate cancer undergone robot-assisted radical prostatectomy at a single institution between 2005 and 2016. The association between time since operation and zero-pad urinary continence recovery was comparatively analyzed by separate pre-operative and post-operative Cox proportional-hazard regression models. RESULTS: Median age in the age group ≥ 70 years was 73 years compared with 62 years in the < 70 year age group. Distribution of men receiving adjuvant and salvage radiotherapy/hormonal therapy was similar in both age groups. Urinary continence recovery rate at 12, 24, and 36 months after surgery of men aged ≥ 70 years was 66, 79 and 83%, respectively, and statistically similar to that of men < 70 years: 71, 81, and 85% (log-rank test p = 0.24). Multivariable analyses demonstrated no significant difference in return to continence between the two age groups (p = 0.28 and p = 0.17). In addition, clinical stage and type of nerve sparing (unilateral, bilateral or non-nerve sparing) were found to be independently predictive of pad-free continence recovery. CONCLUSIONS: Regardless of age, return to continence in men with aggressive prostate cancer undergoing RARP continues to improve way beyond the first 12 months after surgery. Considering the dire effects of post-operative radiotherapy on continence in this aggressive cancer cohort, advanced age alone should not discourage recommending multimodal therapy involving RARP.

Complete bladder neck preservation promotes long-term post-prostatectomy continence without compromising midterm oncological outcome: analysis of a randomised controlled cohort.

PURPOSE: The only RCT available on complete bladder neck preservation (cBNP) during radical prostatectomy reported superior continence and QoL outcomes in the first 12 months after cBNP. We provide the first data on long-term urinary continence, QoL and biochemical recurrence (BCR) after complete bladder neck preservation in a randomised controlled cohort. METHODS: After approval by IRB, 199 men recruited for the randomised, controlled single-blind Heidelberger cBNP Study had prostatectomy performed with (cBNP) or without (noBNP) complete bladder neck preservation. Only men with renewed consent for this follow-up were evaluated for continence, QoL outcomes and BCR by ICIQ-SF self-assessment questionnaire, Pad-use/day and PSA levels. Students-t test, Pearson´s Chi-square, Fishers exact test and multiple logistic regression analyses were applied. RESULTS: Mean follow-up was approx. 4 years. There were no significant differences in baseline characteristics between responders/non-responders or between study groups. We noted significantly higher continence rates (p = 0.004), less pad-use (p < 0.001), reduced frequency (p = 0.023) and amount (p = 0.009) of urine loss, and higher QoL outcomes (p = 0.012) after cBNP. A younger age positively influenced continence (OR = 0.91), but the multivariate analysis found cBNP to be the only independent predictor of continence (p = 0.008; OR = 8.1). pT stage was the only predictor for positive surgical margins (PSM; p < 0.001). There was no significant difference in pT stage (p = 0.23) or BCR (p = 0.63) between study groups and also no significant correlation between BCR and presence (p = 0.26) or localisation (p = 0.11) of PSM, nerve sparing (p = 0.70), surgeon (p = 0.41), preoperative PSA (p = 0.53) or pT stage (p = 0.17). No cancer-related death was noted. CONCLUSIONS: Results of this first follow-up on a prospective randomised controlled cohort demonstrate that cBNP is associated with significantly higher continence and QoL outcomes without compromising cancer control making cBNP a novel objective during radical prostatectomy.

Transpapillary endopancreatic surgery: decompression of duct system and comparison of greenlight laser with monopolar electrosurgical device in ex vivo and in vivo animal models.

BACKGROUND: Endopancreatic surgery (EPS) is an experimental minimally invasive technique for resection of pancreatic tissue from inside the pancreatic duct, accessed via the duodenum and papilla. It is proposed as an alternative to duodenum-preserving pancreatic head resection in benign diseases such as chronic pancreatitis (CP). This study evaluated the use of EPS for resection of pancreatic duct stenoses. Moreover, greenlight laser (GLL) and monopolar electrosurgical device (MES) were compared as resection tools for EPS. METHODS: The suitability of EPS for resection of stenoses was evaluated in ex vivo bovine pancreas (n = 8). Artificially created stenoses in the pancreatic head were accessed via the duodenal papilla and resected from inside the organ with MES through a rigid endoscope. Furthermore, standardized pancreatic resections were performed in an in vivo porcine model using either GLL (n = 18) or MES (n = 18) to compare blood loss, operating time, and complications. Thermal damage to the surrounding tissue was assessed using a standardized histological classification. RESULTS: Stenosis resection by EPS was feasible in 8/8 bovine pancreases, with a procedure time of 17 (12-24) min. No perforation of the organ occurred. Resection by GLL was associated with reduced blood loss [median 1.7 (interquartile range 0.6-2.6) ml vs. 5.1 (3.8-13.2) ml; p < 0.01] and shorter operating time [109 (81-127) s vs. 390 (337-555) s; p < 0.01] compared with MES. The zone of thermal tissue damage was more extensive when using GLL than with MES [4.12 (3.48-4.89) mm vs. 1.33 (1.09-1.48) mm; p < 0.01]. CONCLUSION: Transduodenal-transpapillary EPS can be used to resect stenoses and decompress the pancreatic duct system. Both GLL and MES are feasible resection methods for EPS. However, GLL showed better hemostatic characteristics than MES in an in vivo porcine model. Safety measures such as temperature control and image-guided navigation should be employed to monitor the resection and tissue heating.

Substantial Impairment of Voriconazole Clearance by High-Dose Meropenem in a Patient With Renal Failure.

A critically ill patient with multiple postoperative infections repeatedly required profound voriconazole dose reductions whenever high-dose meropenem was added. Subsequent in vitro assessment confirmed inhibition of cytochrome P450 (CYP) 2C19 and CYP3A4 by meropenem, suggesting that during meropenem treatment, narrow therapeutic index drugs metabolized by these CYPs require close monitoring.

Effective downsizing but enhanced intratumoral heterogeneity following neoadjuvant sorafenib in patients with non-metastatic renal cell carcinoma.

OBJECTIVES: To evaluate the safety and feasibility of sorafenib prior to surgery for downsizing tumors in patients with non-metastatic cT1-3 renal tumors together with a characterization of functional intratumoral heterogeneity (ITH). MATERIALS AND METHODS: The effects of 4-week sorafenib prior to curative surgery were assessed in a prospective, single-center, randomized, placebo-controlled, double-blinded, pilot trial in patients with T1-3N0M0 renal cell carcinoma (RCC). Patients received sorafenib or placebo for 28 days prior to surgery. MRI was performed at baseline and prior to surgery to calculate tumor volume. The clinical responses were further characterized on the molecular level by immunohistochemical stainings for Ki-67, cleaved caspase-3, and CD31. RESULTS: After enrolling 20 patients into the study, 14 patients were randomized, of which 12 patients were available for analysis. While no significant change in tumor volume was seen for placebo (range = -24.2-0.2%) a reduction of 29.0% (range = -4.9-61.1%) was detected for sorafenib (p < 0.05). Primary renal tumor diameter changed from 10.6 cm (range = 6.5-10.8) to 10.7 cm (range = 6.7-11.1) in the placebo group, and from 5.4 cm (range = 4.3-7.3) to 4.4 cm (range = 3.5-6.8) for the sorafenib group, at baseline vs. 28 days of treatment. Correlative assessment of proliferation, apoptosis, and microvessel density revealed an enhanced degree of functional ITH in treated patients suggesting adaptive and/or regenerative processes with potential relevance for the development of drug resistance. CONCLUSIONS: Sorafenib in standard dosage, given preoperatively for 28 days, was clinically active in downsizing tumors in patients with locally confined, non-metastatic RCC together but led to an enhanced functional ITH in the residual tumor tissue.

Diagnostic Accuracy of Transperineal MRI Fusion Biopsy in Comparison to Transrectal Biopsy with Regard to Incidental Histopathological Findings in Transurethral Resection of the Prostate.

OBJECTIVE: To investigate the diagnostic accuracy of transperineal MRI/transrectal ultrasound (TRUS) fusion prostate biopsy vs. transrectal prostate biopsy in transurethral resection (TUR) specimen of men undergoing TUR of the prostate (TURP) for symptomatic bladder outlet obstruction. MATERIAL AND METHODS: From a database of 3,509 men receiving prostate biopsy, all those undergoing TURP and negative prostate biopsy (n = 95; 45 transrectal, 50 transperineal fusion) were analysed. TURP specimens were compared with regard to incidental prostate cancer. RESULTS: Pre- and peri-interventional parameters in transrectal vs. fusion biopsy groups for age (65.2 ± 7.8 vs. 65.5 ± 7.3 years; p = 0.84), prostate specific antigen (10.7 ± 8.5 vs. 10.9 ± 8.7 ng/mL; p = 0.93), preoperative prostate volume (72.5 ± 26.1 vs. 71.8 ± 28.1 mL; p = 0.91) and resected weight (43.7 ± 21.9 vs. 41.4 ± 20.7 g; p = 0.61) showed no significant differences. Analysing the TURP specimen, 5 incidental T1a prostate cancers were found (3 Gleason 3 + 3 = 6; 2 Gleason 3 + 4 = 7, all in the transrectal biopsy group). Although, more biopsy cores were obtained in the MRI/TRUS fusion biopsy group (26 cores [interquartile range, IQR 24-28] vs. 14 cores [IQR 12-24], p < 0.01), there was no statistical impact of the obtained number of cores (p = 0.9) on diagnostic accuracy. Statistical analyses revealed significantly better diagnostic accuracy favoring image-guided fusion biopsy (p = 0.02). CONCLUSIONS: Our findings showed that a combination of MRI-targeted and systematic transperineal prostate biopsy improves patient safety. This is associated with a combination of transperineal biopsy technique and pre-interventional MRI.

Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients.

BACKGROUND: The aim of the study was to reach a consensus on indication and application of a hydrogel spacer based on multicentre experience and give new users important information to shorten the learning curve for this innovative technique. METHODS: The interdisciplinary meeting was attended by radiation oncologists and urologists, each with experience of 23 - 138 hydrogel injections (SpaceOAR®) in prostate cancer patients before dose-escalated radiotherapy. User experience was discussed and questions were defined to comprise practical information relevant for successful hydrogel injection and treatment. Answers to the defined key questions were generated. Hydrogel-associated side effects were collected to estimate the percentage, treatment and prognosis of potential risks. RESULTS: The main indication for hydrogel application was dose-escalated radiotherapy for histologically confirmed low or intermediate risk prostate cancer. It was not recommended in locally advanced prostate cancer. The injection or implantation was performed under transrectal ultrasound guidance via the transperineal approach after prior hydrodissection. The rate of injection-related G2-toxicity was 2% (n = 5) in a total of 258 hydrogel applications. The most frequent complication (n = 4) was rectal wall penetration, diagnosed at different intervals after hydrogel injection and treated conservatively. CONCLUSIONS: A consensus was reached on the application of a hydrogel spacer. Current experience demonstrated feasibility, which could promote initiation of this method in more centres to reduce radiation-related gastrointestinal toxicity of dose-escalated IGRT. However, a very low rate of a potential serious adverse event could not be excluded. Therefore, the application should carefully be discussed with the patient and be balanced against potential benefits.

Ion Prostate Irradiation (IPI) - a pilot study to establish the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique.

BACKGROUND: Due to physical characteristics, ions like protons or carbon ions can administer the dose to the target volume more efficiently than photons since the dose can be lowered at the surrounding normal tissue. Radiation biological considerations are based on the assumption that the α/ß value for prostate cancer cells is 1.5 Gy, so that a biologically more effective dose could be administered due to hypofractionation without increasing risks of late effects of bladder (α/ß = 4.0) and rectum (α/ß = 3.9). METHODS/DESIGN: The IPI study is a prospective randomized phase II study exploring the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique. The study is designed to enroll 92 patients with localized prostate cancer. Primary aim is the assessment of the safety and feasibility of the study treatment on the basis of incidence grade III and IV NCI-CTC-AE (v. 4.02) toxicity and/or the dropout of the patient from the planned therapy due to any reason. Secondary endpoints are PSA-progression free survival (PSA-PFS), overall survival (OS) and quality-of-life (QoL). DISCUSSION: This pilot study aims at the evaluation of the safety and feasibility of hypofractionated irradiation of the prostate with protons and carbon ions in prostate cancer patients in an active beam technique. Additionally, the safety results will be compared with Japanese results recently published for carbon ion irradiation. Due to the missing data of protons in this hypofractionated scheme, an in depth evaluation of the toxicity will be created to gain basic data for a following comparison study with carbon ion irradiation. TRIAL REGISTRATION: Clinical Trial Identifier: NCT01641185 (clinicaltrials.gov).

The impact of type 2 diabetes on the outcome of localized renal cell carcinoma.

PURPOSE: To evaluate the influence of type 2 diabetes on cancer-specific outcome in patients undergoing surgery for localized renal cell carcinoma (RCC). METHODS: A total of 1,140 patients with localized RCC undergoing radical or partial nephrectomy were enrolled into this retrospective case-control study. Primary outcome was the cancer-specific survival comparing patients with and without type 2 diabetes at the time of surgery. Secondary outcomes were recurrence-free survival and metastases-free survival comparing the same groups. Additionally, the influence of accompanying factors on cancer-specific survival and overall survival of patients was evaluated in a multivariate analysis. Among 1,140 patients included in the analyses, 202 had diabetes at the time of surgery and 938 patients without diabetes served as control. RESULTS: The univariate comparisons between patients with and without diabetes regarding recurrence-free, metastases-free, and cancer-specific survival revealed no significant differences. Multivariate results demonstrate that age, BMI, and diabetes had no significant effect on cancer-specific hazard among participants. After adjustment of the factors in terms of overall survival, however, increased age, increased BMI, and type 2 diabetes at the time of surgery were independent risk factors for the occurrence of the event death. CONCLUSIONS: Type 2 diabetes and obesity at the time of surgery have no significant impact on cancer-specific and recurrence-free survival in patients with localized renal cancer.

[Imaging in nephroureterolithasis]. / Bildgebung bei Nephroureterolithiasis.

In the acute diagnostics of a suspected nephroureterolithiasis, ultrasonography should be the examination modality of choice. In cases of suspected urolithiasis, unclear flank pain with fever or in cases of a solitary kidney, a noncontrast computed tomography (CT) scan should always subsequently be performed. If the sonography findings are inconclusive in pregnant women a magnetic resonance imaging (MRI) examination can be considered. If there are indications for urinary diversion, a retrograde imaging study should be performed as part of the urinary diversion. This or CT imaging is also suitable for preinterventional imaging before shock wave lithotripsy, percutaneous nephrolithotomy or ureteroscopy. Postinterventional imaging is not always necessary and sonography is often sufficient. In a conservative treatment approach an abdominal plain X­ray can be used for follow-up assessment.

Application technique: placement of a prostate-rectum spacer in men undergoing prostate radiation therapy.

UNLABELLED: What's known on the subject? and What does the study add? Different spacing agents have been tested to reduce incidential radiation exposure of the rectum during radiotherapy to the prostate. These agents all had certain drawbacks; either the created space was too small or the agents used did not stay in place during radiotherapy treatment. The study describes the transperineal injection technique of a spacing agent in detail. Furthermore it shows the safety and efficacy of the spacing hydrogel used and shows that it overcomes some of the drawbacks of the previously examined spacing agents. OBJECTIVE: • To describe the technique used to apply a hydrogel spacer between the prostate and rectum so as to decrease the radiation dose to the rectum in patients with prostate cancer who are undergoing radiotherapy. METHODS: • A prospective study evaluating the safety and efficacy of prostate-rectum spacer injection was conducted in 29 male patients with prostate cancer scheduled for radiotherapy. • Spacing hydrogel was injected into the perirectal space using a transperineal approach under real-time transrectal ultrasonography guidance. • With the needle tip positioned beyond the rectourethralis muscle, saline injection opened the space between Denonvilliers' fascia and the anterior rectal wall, allowing needle advancement to the mid-prostate without rectal wall injury. Injection of hydrogel precursors further opened this space, which was then maintained as a result of hydrogel polymerization. • Procedure duration and adverse events were monitored. Computed tomography and/or magnetic resonance imaging simulation scans were performed before and after injection. The hydrogel-created space was measured and the reduction in percent volume of the rectum receiving at least 70 Gy (rectal V70) was determined. RESULTS: • Hydrogel injection resulted in mean (sd) additional prostate-rectum space relative to baseline of 9.87 (5.92) mm. • The mean (sd) procedure time, as measured by needle insertion and removal, was 6.3 (3.2) min. • The relative reduction in rectal V70 was 60.6%. • There were no unanticipated adverse events associated with the hydrogel procedure or the hydrogel. CONCLUSIONS: • Hydrogel spacer injection using hydrodissection is a fast and effective procedure to separate the rectal wall from the prostate in order to avoid rectal toxicity. • Hydrogel spacer injection resulted in the addition of ∼1 cm of space • Computed incidental radiation exposure, the rectal V70, was substantially reduced.

Robot-assisted prostatectomy: the new standard of care.

INTRODUCTION: Robot-assisted radical prostatectomy (RARP) has first been performed in 2000 and has since then become a widespread and often performed therapy option for surgical treatment of prostate cancer. The purpose of this review was to highlight the current clinical concepts for radical prostatectomy. DISCUSSION AND CONCLUSIONS: Actual literature search was performed in PubMed database and reviewed. Different surgical techniques for RARP are presented. Oncologic and functional outcomes of RARP are discussed and compared to radical retropubic prostatectomy. In conclusion, RARP has equal oncologic and functional outcome in localized prostate cancer. RARP as a less invasive treatment option for patients with localized prostate cancer should be considered as a new standard of care by now.