Morphologische und molekulare Untersuchungen zur Funktion von Myocilin und Olfactomedin-1 (Pancortin) in der Netzhaut

Myocilin und Olfactomedin-1 (Pancortin) sind Proteine der Olfactomedin-Familie, deren Funktionen bisher weitgehend unbekannt sind. In der vorliegenden Arbeit wurde daher mit Hilfe von Myocilin⁻l⁻-Mäusen versucht, Erkenntnisse über deren Funktion zu gewinnen. Da beide Proteine in der Netzhaut lokalisiert sind und im Falle von Myocilin Gen-Mutationen beim Menschen zur schwerwiegenden Glaukom-Erkrankung führen können, die mit einer Schädigung der Netzhaut einhergeht, wurde ein besonderes Augenmerk auf dieses Gewebe gelegt. Morphologische Untersuchungen von Myocilin⁻l⁻-Mäusen deckten einen neuen, bisher unbekannten Phänotyp auf: So enthalten deren Sehnerven mehr Axone und deren Netzhäute mehr Neuronen in allen Schichten im Vergleich zu den Wildtypen. Der Grund für diesen Befund scheint eine Modulierung des ontogenetischen Zelltods zu sein. TUNEL-Färbungen zeigten, dass Myocilin⁻l⁻-Mäuse zu verschiedenen Zeitpunkten weniger apoptotische Zellen in der Netzhaut aufweisen als die Wildtypen. In weiteren Versuchen wurde deutlich, dass sich die Myocilin-Defizienz nicht nur in der Entwicklung protektiv auswirkt, sondern auch nach Schädigung der retinalen Ganglienzellen durch NMDA und der Photorezeptoren durch Licht. Die Vermutung, dass Myocilin eine pro-apoptotische Rolle spielen könnte, wurde durch in vitro-Experimente bestätigt, in denen RGC-5-Zellen mit Myocilin-haltigem Überstand aus HEK293-Zellen behandelt wurden und dabei in höherem Maße in Apoptose eintraten als die Zellen mit Kontrollbehandlungen. Der Versuch, Signalwege zu identifizieren, die während der Entwicklung für das Überleben der Neurone in den Myocilin⁻l⁻-Tieren verantwortlich sind, blieb insgesamt ohne eindeutiges Ergebnis. Im Gegensatz zu Myocilin⁻l⁻-Mäusen zeigen Pancortin-defiziente Mäuse, die eine mutierte Form des Proteins exprimieren, keine morphologischen Auffälligkeiten in der Netzhaut. Vorversuche der Arbeitsgruppe legen allerdings nahe, dass diese Tiere sensibler auf eine Licht-induzierte Schädigung der Photorezeptoren reagieren als Wildtypen. Dieser Befund wurde anhand von TUNEL-Färbungen voll bestätigt. Die Vermutung, dass Pancortin aufgrund seiner Lokalisation in der Interphotorezeptor-matrix die Rhodopsin-Regeneration beeinflusst, konnte nicht bestätigt werden. Insgesamt wurde in der Arbeit deutlich, dass die beiden untersuchten Olfactomedine unterschiedliche, aber spezifische Wirkungen auf die Netzhaut aufweisen

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

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

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. (C) 2018 S. Karger AG, Basel

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

PurposeHolmium 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.MethodsPreoperative 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.Results60 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 70.3years in the HoLEP and bTURP group, respectively. Median preoperative total PSA was 4.42ng/ml for HoLEP and 4.33ng/ml for bTURP patients. Median preoperative prostate volume was 75.0cc 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.ConclusionsIn 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

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 = 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

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. (C) 2018 Elsevier Inc. All rights reserved

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 (R) 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