Risk factors for bladder neck contracture after transurethral resection of the prostate.

INTRODUCTION: Transurethral resection of the prostate (TURP) is the most frequently used treatment of benign prostate hyperplasia with a prostate volume of <80 mL. A long-term complication is bladder neck contracture (BNC). The aim of the present study was to identify the risk factors for BNC formation after TURP. METHODS: We conducted a retrospective analysis of all TURP primary procedures which were performed at one academic institution between 2013 and 2018. All patients were analyzed and compared with regard to postoperative formation of a BNC requiring further therapy. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify possible risk factors for BNC development. RESULTS: We included 1368 patients in this analysis. Out of these, 88 patients (6.4%) developed BNC requiring further surgical therapy. The following factors showed a statistically significant association with BNC development: smaller preoperative prostate volume (p = 0.001), lower resected prostate weight (p = 0.004), lower preoperative levels of prostate-specific antigen (PSA, p < 0.001), shorter duration of the surgery (p = 0.027), secondary transurethral intervention (due to urinary retention or gross hematuria) during inpatient stay (p = 0.018), positive (≥100 CFU/mL) preoperative urine culture (p = 0.010), and urethral stricture (US) formation requiring direct visual internal urethrotomy (DVIU) postoperatively after TURP (p < 0.001), in particular membranous (p = 0.046) and bulbar (p < 0.001) strictures. Preoperative antibiotic treatment showed a protective effect (p = 0.042). Histopathological findings of prostate cancer (PCA) in the resected prostate tissue were more frequent among patients who did not develop BNC (p = 0.049). On MVA, smaller preoperative prostate volume (p = 0.046), positive preoperative urine culture (p = 0.021), and US requiring DVIU after TURP (p < 0.001) were identified as independent predictors for BNC development. CONCLUSION: BNC is a relevant long-term complication after TURP. In particular, patients with a smaller prostate should be thoroughly informed about this complication.

Onlay Pedicled Transverse Skin Flap versus One-Stage Inlay Buccal Mucosal Graft in Penile Urethroplasty: A Prospective Matched-Pair Analysis.

INTRODUCTION: The aim of this study was to compare urethroplasty using onlay pedicled transverse skin flap (PSF) versus one-stage inlay buccal mucosa graft (BMG) in repair of penile urethral strictures. METHODS: We conducted a prospective matched-pair analysis of 44 male patients receiving penile urethroplasty between June 2016 and June 2019. There were 22 patients who received PSF and 22 patients who received BMG. Matching was performed according to stricture length. Patients with strictures caused by lichen sclerosus, prior hypospadias repair, or failed prior urethroplasty were excluded. Treatment was considered successful if no recurrence was observed. Successful repair, complication rates, patients' satisfaction, and quality of life improvement were endpoints of this study. RESULTS: Mean follow-up was 40.3 months. PSF and BMG showed comparable success rates (90.9% vs. 86.4%, p = 0.713). Recurrent stricture occurred in 2 patients (9.1%) who received PSF and in 3 patients (13.6%) who received BMG. Operation time was significantly longer for PSF than for BMG (108.4 min vs. 78.1 min, p = 0.01). Univariable logistic regression analysis revealed no relevant risk factors for stricture recurrence. CONCLUSION: Early results indicate comparable success rates of PSF and BMG in penile urethroplasty. Further studies with larger sample size and longer follow-up periods are required to evaluate subtle differences between both techniques.

Early Revision after Artificial Urinary Sphincter Implantation Does Not Impair the Long-Term Treatment Success.

INTRODUCTION: After implantation of an artificial urinary sphincter (AUS) due to stress urinary incontinence, in some cases revision procedures may be necessary. This is mostly due to device infection or cuff erosion in the long term. The aim of this study was to evaluate the impact of early revision procedures (prior to or immediately after AUS activation) on the long-term outcome. METHODS: We retrospectively evaluated patients who underwent primary AUS implantation between 2006 and 2019. Patients with previous radiotherapy, urethroplasty, urethral stent placement, or repeat AUS implantation were excluded. Early revision was defined as prior to or immediately after AUS activation and comprised pump repositioning or cuff size adaptation due to difficulties in using the pump, persistent urinary incontinence, or urinary retention. Patients were compared with regard to complication rates, functional outcome, and patient satisfaction. Univariable and multivariable logistic regression analyses were performed to analyze risk factors for early AUS revision. Kaplan-Meier analysis evaluated explantation-free survival. RESULTS: A total of 250 patients were included. Twenty patients (8%) required early revision (pump repositioning in 15 cases [75%], cuff downsizing in 3 cases [15%], and cuff upsizing in 2 cases [10%]). Mean follow-up was 78.6 months. 96.4% of all patients were objectively continent at the time of last follow-up without differences between both groups, and patient satisfaction was high in both groups. No differences with regard to mechanical implant failure, tissue atrophy, and AUS explantation due to cuff erosion or implant infection were observed. Explantation-free survival was comparable in both groups. On univariable logistic regression analysis, coronary artery disease and transcorporal cuff placement were associated with early AUS revision. CONCLUSION: Early revision after AUS implantation can be performed without negative impact on the long-term outcome.

High BMI, Aggressive Tumours and Long Console Time Are Independent Predictive Factors for Symptomatic Lymphocele Formation after Robot-Assisted Radical Prostatectomy and Pelvic Lymph Node Dissection.

INTRODUCTION: Lymphocele (LC) formation is a common complication which may cause severe symptoms after robot-assisted radical prostatovesiculectomy (RARP) with concomitant pelvic lymph node dissection (PLND). Compared to open radical prostatectomy, the amount of data on potential risk factors for LC formation is still limited. The aim of the present study was to identify risk factors for symptomatic LC formation (sLC) after RARP with PLND. METHODS: We used the data of a prospective multicentre series of 232 RARP patients which were treated between March 2017 and December 2017. The primary endpoint was the presence of sLC within 90 days. Asymptomatic LC (aLC) formation was also recorded. We evaluated clinical, perioperative, and histopathological criteria and compared their distribution in patients with and without post-operative sLC. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify potential predictors for LC formation. Regarding the influence of patients' BMI, 2 models were calculated: BMI continuously (model 1) and BMI dichotomized with cut-off 30 kg/m2 (WHO definition, model 2). RESULTS: Post-operative sLC was present in 21 patients (9.1%), while aLC was detected in 49 patients (21.1%) 90 days after RARP with PLND. Patients with sLC showed higher median baseline PSA levels (9.8 vs. 8.1 ng/mL), higher prevalence of obesity (BMI >30; 42.9 vs. 19.9%), and longer median console time (180 vs. 165 min) compared to patients without sLC. On MVA higher BMI {model 1: OR 1.145 (confidence interval [CI] 1.025-1.278); model 2: OR 2.761 (1.045-7.296)}, longer console time (model 1: OR 1.013 [1.005-1.021]; model 2: OR 1.013 [1.005-1.020]) and an ISUP grade ≥3 (model 1: OR 3.247 [1.182-8.917]; model 2: OR 2.791 [1.050-7.423]) were identified as independent predictors for sLC development. CONCLUSION: Patients with aggressive tumours and higher BMI should be informed about a potentially increased risk for sLC formation. In case of a long console time, a close and regular follow-up should be considered to check for LC development.

Impact of previous urethroplasty on the outcome after artificial urinary sphincter implantation: a prospective evaluation.

PURPOSE: To evaluate the impact of previous urethroplasty on complication rates and postoperative continence after primary artificial urinary sphincter (AUS) implantation in male patients with severe stress urinary incontinence. PATIENTS AND METHODS: A prospective evaluation of patients undergoing primary AUS implantation was conducted. Patients with previous radiotherapy, AUS implantation or urethral stent placement were excluded. Main endpoints were postoperative continence and complication rates including necessity of AUS explantation. Kaplan-Meier analysis evaluated explantation-free survival. Logistic regression analyses were performed to identify potential predictors for AUS explantation. RESULTS: 105 patients were included with a mean follow-up of 76.6 months (SD 15.9). 30 of these patients had a history of urethroplasty. Postoperatively, 96.2% of all patients were objectively continent (≤ 1 pad/day). No differences in postoperative continence and early complication rates were observed. Concerning long-term complications, infection, mechanical implant failure, and tissue atrophy were also comparable. Overall sphincter erosion rate was 12.3%, but significantly higher in urethroplasty patients (23.3% vs. 8.0%, p = 0.038) and sphincter explantation rate was threefold higher (p = 0.016) in the urethroplasty group. Furthermore, explantation-free survival was reduced compared to the non-urethroplasty group (p = 0.044). On logistic regression analysis, the previous urethroplasty was the only significant predictor for AUS explantation (p = 0.016). CONCLUSION: AUS implantation in patients with former urethroplasty can provide satisfying results. Compared to patients without the previous urethroplasty, the higher risk of cuff erosion and AUS explantation has to be addressed during preoperative consultation. Patients with the previous urethroplasty with grafting, long strictures and previous visual internal urethrotomy might be at highest risk.

Introduction of a New Score to Assess Surgical Efficiency in Holmium Laser Enucleation of the Prostate.

INTRODUCTION: While holmium laser enucleation of the prostate (HoLEP) is accepted as safe and efficient, a long learning curve is considered the main reason for its slow adoption in clinical practice. So far, no standardized and easy-to-use parameter has been implemented to measure surgical experience or efficiency which could be useful for training and quality control purposes. The aim of the present study was to evaluate the learning curves of 2 HoLEP beginners and to identify applicable efficiency outcome measures as well as potentially complicating factors in performing HoLEP. PATIENTS AND METHODS: A total of 594 patients treated by HoLEP between September 2016 and May 2019 were enrolled. The procedures were initially performed by 1 HoLEP expert (reference surgeon); over time, 2 further surgeons were trained. Baseline characteristics, enucleation weight, morcellation and enucleation time, laser energy usage, and postoperative results were recorded prospectively. The learning curves of the 2 novices were analyzed and compared to the reference surgeon. Logistic regression analyses were performed to identify predictors for postoperative grade ≥2 complications. RESULTS: Median enucleation ratio and complication rates did not significantly alter along the learning curves. Median enucleation speed and laser energy application of the 2 novices significantly improved with growing experience. Combining these variables, we introduced the "HoLEP efficiency score" (HES) which demonstrated the most appropriate value to reflect the surgical experience and efficiency. The median HES for the reference surgeon was 82.8 min kJ/g. For the 2 novices, a drop from 130 and 124.4 min kJ/g by -57 and -30%, respectively, was observed. Among several tested clinical parameters, the presence of prostate cancer (p = 0.047) and the surgical caseload (p < 0.001) influenced the HES. On multivariable logistic regression, American Society of Anesthesiologists score and prostate cancer were independent predictors for grade ≥2 complications (p = 0.002, odds ratio [OR] 2.042 and p = 0.038, OR 1.940). CONCLUSION: We introduce the HES as an objective and measurable tool to quantify surgical efficiency. In clinical practice, the HES may find application in training and quality control purposes as well as in comparing surgical modifications and hardware. Patients with prostate cancer seem to be more challenging cases and have a higher risk for complications, and may preferably be treated by experienced surgeons.

Oncological long-term outcome of whole gland HIFU and open radical prostatectomy: a comparative analysis.

PURPOSE: To compare the oncological long-term efficacy of whole gland high-intensity focused ultrasound (HIFU) therapy and radical prostatectomy (RP) in patients with clinically localized prostate cancer. METHODS: 418 patients after open RP (1997-2004) were compared with 469 patients after whole gland HIFU (1997-2009) without preselection. Oncological follow-up focused on biochemical relapse, salvage treatment, life status and cause-specific mortality. The univariate log rank test was used to compare both treatment options regarding overall survival (OS), cancer-specific survival (CSS), biochemical failure-free survival (BFS) and salvage treatment-free survival (STS). To adjust the treatment effect for further prognostic baseline variables, a multivariable Cox proportional hazards regression model was calculated for each end point. RESULTS: Median follow-up was 13.3 years in the RP group and 6.5 years in the HIFU group. OS/CSS/BFS/STS rates at 10 years were 91/98/80/80% after RP and 76/94/70/71% after HIFU. HIFU therapy (reference RP) was a significant and independent predictor for an inferior OS, CSS and STS. In subgroup analysis, HIFU provided significantly reduced CSS for intermediate- (p = 0.010) and high-risk patients (p = 0.048); whereas no difference was observed in the low-risk group, intermediate-risk HIFU patients showed a significantly inferior STS (p = 0.040). CONCLUSIONS: While whole gland HIFU offers a comparable long-term efficacy for low-risk patients, sufficient cancer control for high-risk patients is more than doubtful. For the subgroup of intermediate-risk patients, CSS rates seem to be comparable up to 10 years suggesting that HIFU may be an alternative for older patients, although a higher risk of salvage treatment should be expected.

Oncological Outcome and Value of Postoperative Magnetic Resonance Imaging after Focal High-Intensity Focused Ultrasound Therapy for Prostate Cancer.

INTRODUCTION: Focal therapy (FT) by high-intensity focused ultrasound (HIFU) is an emerging option for localized prostate cancer (PC). Due to the lack of long-term data, a close monitoring after FT is essential, but there are still uncertainties about the optimal follow-up regimen. Here we report on a series of FT-HIFU patients with the focus on oncological short-term outcome and the value of postoperative magnetic resonance imaging (MRI). METHODS: We included 21 patients treated by FT-HIFU using the Focal One® device (EDAP TMS, France) between November 2015 and May 2018. PC localization was assessed by preoperative multiparametric MRI (mpMRI) and transrectal ultrasound-guided targeted and systematic biopsy. Oncological follow-up included prostate-specific antigen (PSA) development, mpMRI, control biopsies (targeted and systematic) of the treated and untreated areas and salvage treatment rate. Control mpMRI and control biopsy were performed after 6-12 months. RESULTS: 15 patients (71.4%) were managed by focal ablation of a solitary lesion, while 6 patients (28.6%) underwent zonal tumor ablation. All patients underwent control mpMRI and biopsy. After a mean follow-up period of 11.7 months, cancer relapse was detected in 8 patients (38.1%), with 4 patients (19%) having infield recurrence. Postoperative mpMRI revealed 3 out of 4 infield PC relapses but missed 5 out of 7 outfield relapses. Clinically significant cancer recurrence was present in 1 patient (4.8%), which was missed by mpMRI. Posttreatment mpMRI had a sensitivity, specificity, positive and negative predictive value of 62.5, 92.3, 83.3 and 80.0%, respectively, for overall relapse detection based on patient level. Only 1 of the 8 recurrences was suspected based on PSA progression. 4 of the 8 patients with PC relapse (19%) underwent salvage therapy (2 patients by radical prostatectomy, 2 patients by salvage FT-HIFU). CONCLUSION: Postoperative mpMRI might play a valuable role during follow-up after focal HIFU therapy, particularly in terms of infield relapse detection. Irrespective of mpMRI results, the repeat biopsy regimen should incorporate systematic biopsy including cores of the treated and untreated prostate areas.

HoLEP provides a higher prostate cancer detection rate compared to bipolar TURP: a matched-pair analysis.

PURPOSE: Holmium laser enucleation of the prostate (HoLEP) has become a popular alternative to TURP for desobstructive prostate surgery. The prevalence of incidental prostate cancer (iPCa) during surgery varies depending on many preoperative factors. To evaluate whether the surgical procedure itself (HoLEP vs. TURP) influences iPCa detection, we performed a case-by-case matched-pair analysis. METHODS: Preoperative patient age, total PSA, and prostate volume were used as matching criteria. Descriptive statistics were used to confirm matching quality. Parameters were analyzed by Fisher's exact test and T test or Mann-Whitney U test for dichotomous and continuous variables, respectively. Uni- and multivariate logistic regression analyses were performed to identify predictors for iPCa detection. RESULTS: 60 out of 136 patients after HoLEP and 60 out of 1220 patients after bipolar TURP (bTURP) could be included. Mean patient age was 71.5 and 70.3 years in the HoLEP and bTURP group, respectively. Median preoperative total PSA was 4.42 ng/ml for HoLEP and 4.33 ng/ml for bTURP patients. Median preoperative prostate volume was 75.0 cc in both groups. Mean percentage of tissue removed by HoLEP and bTURP was 63.5 and 49.5% (p < 0.001), respectively. IPCa was found in 23.3% of HoLEP specimens compared to 8.3% in bTURP (p = 0.043). PSA density was the only independent predictor for iPCa detection. CONCLUSIONS: In this first matched-pair analysis, HoLEP provides a significantly higher iPCa detection rate than bTURP. This might be a result of a more efficient tissue removal during HoLEP. PSA density was the only independent risk factor for iPCa.

Expression, localisation and potential significance of aquaporins in benign and malignant human prostate tissue.

BACKGROUND: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. METHODS: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. RESULTS: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = - 0.354; p = 0.013), D'Amico risk stratification (ρ = - 0.336; p = 0.012), ISUP grade (ρ = - 0.321; p = 0.017) and Gleason score (ρ = - 0.342; p = 0.011). CONCLUSIONS: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

Holmium Laser Enucleation of the Prostate Provides Similar Incidental Prostate Cancer Detection Rates as Open Prostatectomy: A Matched Pair Analysis.

INTRODUCTION: Whereas the excellent functional outcomes after Holmium laser enucleation of the prostate (HoLEP) and its equivalency to open prostatectomy (OP) have been studied in detail in the past years, the oncological equivalency has yet to be investigated. Therefore, we conducted a matched pair analysis to evaluate and compare incidental prostate cancer detection rates after HoLEP and OP. PATIENTS AND METHODS: Preoperative patient age, total prostate-specific antigen (PSA), and prostate volume were used as primary matching criteria. Descriptive statistics were used to confirm matching quality. Statistical analyses were performed using Fisher´s exact test and T-test or Mann-Whitney U-test for dichotomous and continuous variables, respectively. RESULTS: After the matching procedure, 72 out of 145 patients after HoLEP and 72 out of 477 patients after OP were included. Mean patient age (70 vs. 71 years), median prostate volume (106 vs. 107 mL), and median preoperative total PSA (4.32 vs. 4.36 ng/mL) were almost identical. The amount of removed tissue did not differ between HoLEP and OP. Incidental prostate cancer detection rate was similar with 9.7% after HoLEP and 8.3% after OP (p = 1.000). CONCLUSION: This first matched pair analysis shows that HoLEP does not have a disadvantage regarding cancer detection rate during desobstructive surgery for large prostates.

Prospective Evaluation of Predictive Parameters for Urinary Tract Infection in Patients with Acute Renal Colic.

BACKGROUND: Acute renal colic (ARC) is an emergency that can mostly be treated conservatively, but can be life threatening in combination with urinary tract infection (UTI). Assessment for infection includes white blood cell (WBC) count and C-reactive protein (CRP), but these parameters are often unspecifically elevated and might lead to antibiotic over-therapy. In times of increasing antibiotic resistance, however, unnecessary antibiotic therapy should be avoided. OBJECTIVES: The goal of the study was to investigate the prevalence of UTI proven by urine culture (UC) in patients with ARC and to identify predictive factors in the emergency setting. PATIENTS AND METHODS: We prospectively enrolled 200 consecutive patients with ARC and evaluated blood test results, urinalysis, UC, symptoms suspicious for UTI, and time between symptom onset and admission, as well as body temperature. Logistic regression analyses were performed to identify predictive factors. RESULTS: There were 196 patients eligible for statistical analysis. UTI proven by positive UC was detected in 26 patients (13%). On multivariate logistic regression analysis, suspicious urinalysis (positive nitrite or bacteria > 20/high-power field [hpf] or WBC > 20/hpf), patient age ≥ 54 years and CRP ≥ 1.5 mg/dL (fivefold increase) were significant predictors for the presence of UTI. Neither elevated WBC count nor typical UTI symptoms were associated with UTI. CONCLUSIONS: Based on our results, a routine antibiotic prophylaxis in patients with ARC does not seem to be appropriate. Patient age and CRP can help to decide if antibiotic treatment might be indicated, even in case of a not clearly suspicious urinalysis.

Mutated olfactomedin 1 in the interphotoreceptor matrix of the mouse retina causes functional deficits and vulnerability to light damage.

Olfactomedin 1 (OLFM1) is a secreted glycoprotein and member of the olfactomedin protein family, which is preferentially expressed in various areas throughout the central nervous system. To learn about the functional properties of OLFM1 in the eye, we investigated its localization in the mouse and pig eye. In addition, we analyzed the ocular phenotype of Olfm1 mutant mice in which 52 amino acids were deleted in the central part (M2 region) of OLFM1. OLFM1 was detected in cornea, sclera, retina, and optic nerve of both wild-type and Olfm1 mutant littermates. By immunohistochemistry and double labeling with the lectin peanut agglutinin, OLFM1 was found in the interphotoreceptor matrix (IPM) of mouse and pig retina where it was directly localized to the inner segments of photoreceptors. Western blotting confirmed the presence of the OLFM1 isoforms pancortin 1 (BMY) and pancortin 2 (BMZ) in the IPM. The retinal phenotype of Olfm1 mutant mice did not obviously differ from that of wild-type littermates. In addition, outer nuclear layer (ONL) and total retinal thickness were not different, and the same was true for the area of the optic nerve in cross sections. Functional changes were observed though by electroretinography, which showed significantly lower a- and b-wave amplitudes in Olfm1 mutant mice when compared to age-matched wild-type mice. When light damage experiments were performed as an experimental paradigm of photoreceptor apoptosis, significantly more TUNEL-positive cells were observed in Olfm1 mutant mice 30 h after light exposure. One week after light exposure, the ONL was significantly thinner in Olfm1 mutant mice than in wild-type littermates indicating increased photoreceptor loss. No differences were observed when rhodopsin turnover or ERK1/2 signaling was investigated. We conclude that OLFM1 is a newly identified IPM molecule that serves an important role for photoreceptor homeostasis, which is significantly compromised in the eyes of Olfm1 mutant mice.

Myocilin modulates programmed cell death during retinal development.

Mutations in the myocilin gene (MYOC) are causative for 10% of cases with juvenile open-angle glaucoma and 3-4% of those with primary open-angle glaucoma. Myocilin is a secreted protein with relatively ill-defined matricellular properties. Despite its high expression in the eye, myocilin-deficient mice have originally been reported to have no obvious ocular phenotype. Here we revisited the ocular phenotype of myocilin-deficient mice and detected a higher number of neurons in their inner (INL) and outer (ONL) nuclear layers, as well as a higher number of retinal ganglion cells (RGC) and their axons. The increase in retinal neurons appears to be caused by a decrease in programmed developmental cell death, as apoptosis of retinal neurons between postnatal days 4 and 10 was found to be attenuated when compared to that of wildtype littermates. In contrast, when Myoc(-/-) mice were crossed with ßB1-crystallin-MYOC mice with ectopic overexpression of myocilin in the eye, no differences in developmental apoptosis, RGC number and INL thickness were observed when compared to wildtype littermates. The amounts of the anti-apoptotic Bcl-2-like protein 1 (BCL2L1, Bcl-xL) and its mRNA were increased in retinae of Myoc(-/-) mice, while lower amounts of BCL2L1 and its mRNA were detected in mixed Myoc(-/-)/ßB1-crystallin-MYOC mice. The structural differences between Myoc(-/-) mice and wildtype littermates did not result in functional differences as measured by electroretinography. Noteworthy though mixed Myoc(-/-)/ßB1-crystallin-MYOC mice with ocular overexpression of myocilin had significant cone function deficits. Myocilin appears to modulate apoptotic death of retinal neurons likely by interacting with the intrinsic apoptotic pathway.

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract.

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02-3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18-3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification.

Oncological Long-term Outcome After Whole-gland High-intensity Focused Ultrasound for Prostate Cancer-21-yr Follow-up.

BACKGROUND: Owing to the morbidity of established radical treatment options for prostate cancer, alternative whole-gland and focal treatment strategies have emerged. High-intensity focused ultrasound (HIFU) is one of the most studied sources for tissue ablation and has been used since the 1990s. OBJECTIVE: To provide 21-yr oncological long-term follow-up data of an unselected series of patients who underwent whole-gland HIFU for nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 674 patients were treated between November 1997 and November 2012 in one university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The oncological outcome was assessed by biopsy failure-free survival (BFFS), salvage treatment-free survival (STFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazard regression analyses were performed to estimate the prognostic relevance of clinical variables. RESULTS AND LIMITATIONS: In total, 560 patients were included into the evaluation and the median follow-up was 15.1 yr, with a range up to 21.4 yr. At 15 yr, CSS rates for low-, intermediate-, and high-risk patients were 95%, 89%, and 65%, respectively; MFS, STFS-1 (salvage treatment other than HIFU), STFS-2 (salvage treatment including repeat HIFU), and BFFS rates were 91%, 85%, and 58%; 77%, 63%, and 29%; 67%, 52%, and 28%; and 82%, 73%, and 47%, respectively. Preoperative high-risk category was an independent predictor of inferior OS, CSS, MFS, STFS, and BFFS. CONCLUSIONS: Although whole-gland HIFU achieved good long-term cancer control in low- and intermediate-risk patients, high-risk patients should not be treated routinely by HIFU. Intermediate-risk patients achieve high CSS and MFS rates, but a relevant salvage treatment rate has to be reckoned with. Long-term data after whole-gland therapy might help derive implications for focal treatment sources and patient selection. PATIENT SUMMARY: Long-term data after whole-gland high-intensity focused ultrasound (HIFU) therapy are crucial to prove its oncological efficacy, and may help derive implications for focal treatment strategies and patient selection. In this context, whole-gland HIFU achieved good long-term cancer control up to 21 yr in low- and intermediate-risk prostate cancer (PCa) patients. Owing to considerably inferior long-term cancer control, it should not routinely be used in high-risk PCa patients.

Prognostic Role of mRNA-Expression of Aquaporins (AQP) 3, 4, 7 and 9 in Stage pT1 Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: AQP proteins show a variety of functions in human cell metabolism. The role of different AQP subtypes in tumor metabolism and prognosis are subject of ongoing research. OBJECTIVE: To investigate the mRNA expression of Aquaporin (AQP) 3, 4, 7 and 9 in pT1 non-muscle-invasive bladder cancer (NMIBC) and its prognostic value in therapeutic decision making. METHODS: Formalin-fixed-paraffin-embedded (FFPE) tissues from transurethral resection of the bladder (TURB) from 112 patients with initial diagnosis of stage pT1 NMIBC were analyzed retrospectively together with clinical data and therapeutic approaches. mRNA expression of AQP3, 4, 7 and 9 was measured and quantified using RT-qPCR. RESULTS: Of the 112 patients (83.9%male, median age 72 years), 40 had a recurrence (35.7%), 16 a progression (14.3%) and 14 patients (12.5%) died tumor-related. mRNA expression for AQP3 was detected in 99.1%, AQP4 in 46.4%, AQP7 in 86.6%and AQP9 in 97.3%. Spearman analysis revealed statistically significant correlations between AQP3, AQP7 and AQP9 mRNA expression with adverse clinical and histopathological parameters (WHO1973 grade 3, concomitant Cis or multifocality). High AQP9 mRNA expression was associated with worse PFS in the total cohort (p = 0.034) and in Grade 3 tumors (p = 0.003) in Kaplan-Meier analysis. In patients with bladder sparing approach, high AQP3 mRNA expression was significantly associated with worse CSS in patients receiving BCG therapy (p = 0.029). CONCLUSIONS: mRNA expression of AQP3, 7 and 9 correlates with adverse clinical and pathological parameters. AQP3 and 9 may help to identify a subgroup of highest risk patients who may be considered for early cystectomy.

Peritoneal Flap in Robot-Assisted Radical Prostatectomy.

BACKGROUND: Lymphocele is the most common complication arising after pelvic lymph node dissection (PLND) in the setting of robot-assisted radical prostatectomy (RARP). The only data available until now on the utility of a peritoneal flap to prevent lymphocele were retrospectively acquired. METHODS: A randomized, controlled, multi-center trial with blinded assessment of endpoints was carried out on 232 patients with prostate cancer who underwent RARP with PLND. The patients in the intervention group were given a peritoneal flap; in the control group, surgery was performed without this modification. The two joint primary endpoints were the rates of symptomatic lymphocele during the same hospitalization as the operative procedure (iT1) and within 90 days of surgery (iT2). The secondary endpoints were lymphocele volume, the need for treatment of lymphocele, complications requiring an intervention, and the degree of postoperative stress incontinence. German Clinical Trials Register number: DRKS00011115. RESULTS: The data were evaluated in an intention-to-treat analysis, which, in this trial, was identical to an as-treated analysis. 108 patients (46.6%) were allotted to the intervention group. There were no statistically significant intergroup differences with respect to any clinical or histopathological criteria. A median of 16 lymph nodes were removed (interquartile range, 11-21). A symptomatic lymphocele arose in 1.3% (iT1) and 9.1% (iT2) of the patients, without any statistically significant difference between the two trial groups (p = 0.599 and p = 0.820, respectively). Nor did the groups differ significantly with respect to lymphocele volume (p = 0.670 on hospital discharge [T1], p = 0.650 90 days after surgery [T2]) or the type and frequency of need for subsequent surgical intervention (p = 0.535; iT2). 81.5% of all patients (n = 189) had no complications at all in the first three months after surgery. Nor were there any intergroup differences at 90 days with respect to the degree of stress urinary incontinence (p = 0.306) or complications (p = 0.486). CONCLUSION: A peritoneal flap after RARP was not found to influence the rate of postoperative lymphocele, whether asymptomatic or requiring treatment.

Obesity leads to a higher rate of positive surgical margins in the context of robot-assisted radical prostatectomy. Results of a prospective multicenter study.

INTRODUCTION: Current results concerning the effect of body mass index (BMI) on positive surgical margins (PSMs) after robot-assisted radical prostatectomy (RARP) in patients with localized prostate cancer are inconsistent. Therefore, the aim of this study was to further analyse the association between BMI and PSMs after RARP. MATERIAL AND METHODS: Between March 2017 and December 2017 a multicentre, prospective, randomised, single-blind series with a blinded outcome assessment of 232 RARP patients was performed. Multivariate logistical regression models were used to analyse the independent effect of obesity, with body-mass-index (BMI) dichotomised at 30 kg/m2 (model-1) and at 90th percentile (model-2), on PSMs. RESULTS: Median BMI was 27.2 kg/m2, PSMs were found in 15.5% (n = 36). In multivariate model-1, obesity did not have a significant effect on PSMs (OR 2.34, p = 0.061). However, if BMI was dichotomized at the 90th percentile (BMI ≥33.7 kg/m²), patients with a higher BMI showed PSMs four-times more frequently (OR 3.99, p = 0.013). In both models, preoperative prostate-specific antigen (PSA) levels and pathological tumour stage had a significant effect on PSMs. There was no significant correlation between BMI and the extent of PSMs, nor a significant difference between the BMI groups and the localisation of PSMs. There was a higher percentage of posteriolateral PSM localisation in obese patients compared to patients with a BMI of less than 30 kg/m2 (58.3% and 25.3% of the localisations were posterolateral in obese and non-obese patients, respectively), however this effect was not statistically significant (p = 0.175). CONCLUSIONS: In addition to a longer operation time and about twice as many complications, patients with a BMI of ≥33.7 kg/m² had a higher PSM rate after RARP. Differences in localization of PSMs in relation to obesity should be evaluated in future research.