Which Men Do or Do Not Achieve Long-Term Symptom Relief After Holmium Laser Enucleation of the Prostate (HoLEP): 11 Years of HoLEP Experience.

Purpose: Apart from the existing level-one evidence, few centers have reported on long-term outcomes after Holmium Laser Enucleation of the Prostate (HoLEP). Against this backdrop we aimed to report on our treatment experience and identify predictors of persistent/recurrent lower urinary tract symptoms (LUTS) after the procedure. Materials and Methods: From 2006 to 2017, 2566 men underwent HoLEP at our institution. Only patients with available, cross-sectional follow-up (F/u) ≥6 months were included. Perioperative and F/u characteristics were compared by duration of F/u in months (quartiles). Multivariable logistic regression models (MVAs) were used to identify predictors of persistent/recurring symptoms, defined as International Prostate Symptom Score (IPSS) >7 at F/u. Results: A total of 774 patients with a median age of 70 years (interquartile range [IQR] = 66-75), prostate volume of 80 mL (IQR = 60-105), American Society of Anesthesiologists score 2 (IQR = 2-3), IPSS of 19 (IQR = 14-24), and quality of life (QoL) of 4 (3-5) at the time of operation were analyzed. Median F/u was 52 months (IQR = 32-77), overall current median prostate-specific antigen was 0.91 mg/dL (0.5-1.8), median IPSS and QoL were 3 (IQR = 1-7) and 1 (IQR 0-2), respectively. LUTS medication was present in 20 patients (2.6%), 15 (2%) patients required reoperation, and permanent urinary incontinence was present in 17 (2.2%) patients. On MVA age at operation (odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.1; p = 0.013), prostate volume (OR = 0.99 [95% CI, 0.98-0.99;], p = 0.003), body mass index (OR = 1.06 [95% CI, 1.0-1.1], p = 0.043), presence of indwelling catheter (OR = 0.51 [95% CI, 0.32-0.81], p = 0.004), and anticholinergics before procedure (OR = 1.74 [95% CI, 1.01-3.0], p = 0.046) were predictors of persistent/recurring symptoms. Conclusions: Our HoLEP experience confirms durable and profound symptom relief in the vast majority men. A small fraction of patients complained about subjective persistent/recurring LUTS stressing the need for proper patient selection and timing of surgical intervention.

The significance of the extent of tissue embedding for the detection of incidental prostate carcinoma on transurethral prostate resection material: the more, the better?

The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium-aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1-38) vs. a median of 15 (range 2-74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.

Nomogram Predicting Downgrading in National Comprehensive Cancer Network High-risk Prostate Cancer Patients Treated with Radical Prostatectomy.

BACKGROUND: Some high-risk prostate cancer (PCa) patients may show more favorable Gleason pattern at radical prostatectomy (RP) than at biopsy. OBJECTIVE: To test whether downgrading could be predicted accurately. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results database (2010-2016), 6690 National Comprehensive Cancer Network (NCCN) high-risk PCa patients were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: We randomly split the overall cohort between development and validation cohorts (both n = 3345, 50%). Multivariable logistic regression models used biopsy Gleason, prostate-specific antigen, number of positive prostate biopsy cores, and cT stage to predict downgrading. Accuracy, calibration, and decision curve analysis (DCA) tested the model in the external validation cohort. RESULTS AND LIMITATIONS: Of 6690 patients, 50.3% were downgraded at RP, and of 2315 patients with any biopsy pattern 5, 44.1% were downgraded to RP Gleason pattern ≤4 + 4. Downgrading rates were highest in biopsy Gleason pattern 5 + 5 (84.1%) and lowest in 3 + 4 (4.0%). In the validation cohort, the logistic regression model-derived nomogram predicted downgrading with 71.0% accuracy, with marginal departures (±3.3%) from ideal predictions in calibration. In DCA, a net benefit throughout all threshold probabilities was recorded, relative to treat-all or treat-none strategies and an algorithm based on an average downgrading rate of 50.3%. All steps were repeated in the subgroup with any biopsy Gleason pattern 5, to predict RP Gleason pattern ≤4 + 4. Here, a second nomogram (n = 2315) yielded 68.0% accuracy, maximal departures from ideal prediction of ±5.7%, and virtually the same DCA pattern as the main nomogram. CONCLUSIONS: Downgrading affects half of all high-risk PCa patients. Its presence may be predicted accurately and may help with better treatment planning. PATIENT SUMMARY: Downgrading occurs in every second high-risk prostate cancer patients. The nomograms developed by us can predict these probabilities accurately.

Cancer-specific mortality after radical prostatectomy vs external beam radiotherapy in high-risk Hispanic/Latino prostate cancer patients.

PURPOSE: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT). METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage). RESULTS: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19-0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21-1.39, p = 0.2). CONCLUSION: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome.

Assessing the Outcome of Holmium Laser Enucleation of the Prostate by Age, Prostate Volume, and a History of Blood Thinning Agents: Report from a Single-Center Series of >1800 Consecutive Cases.

Purpose: To assess perioperative outcomes of holmium laser enucleation of the prostate (HoLEP) in a real-world scenario and with a focus on demanding patient factors, such as large prostate size, advanced patient age, and anticoagulation therapy (AT). Materials and Methods: We retrospectively analyzed HoLEP procedures at our institution between 2010 and 2016. After stratification by prostate volume, age, and AT, perioperative and early voiding characteristics were compared. A multivariable regression model was employed to identify predictors of prolonged time of catheterization (defined as being above group's median). Results: The study cohort consisted of 1816 men with a median age of 71 years (interquartile range [IQR]: 66-76), a median prostate volume of 80 mL (IQR: 58-105), and American Society of Anesthesiologists score ≥3 in 618 men (34%). Median time of enucleation and morcellation was 43 minutes (IQR: 31-60) and 10 minutes (IQR: 6-18), respectively. Perioperative blood transfusions were administered in 44 (2.4%) cases, severe postoperative complications (Clavien-Dindo grade ≥3b) occurred in 61 (3.3%) cases. The median time of catheterization was 2 days (IQR: 2-2), with prolonged catheterization occurring in 277 (15%) cases. After adjustment, large prostates (fourth volume quartile [106-280 mL]) (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.3-2.6, p = 0.001), therapeutic low-molecular-weight heparin bridging regimen (OR: 2.2, 95% CI: 1.4-3.6, p = 0.037), low-dose acetylsalicylic acid (OR: 1.5, 95% CI: 1.0-2.2, p = 0.015), and a history of direct oral anticoagulation (OR: 2.3, 95% CI: 1.2-4.0, p = 0.022), but not patient age, were independently associated with prolonged catheterization. Conclusions: We confirm HoLEP as safe and efficient; however, patients with large prostates and patients with a history of AT are at risk of prolonged catheterization.

Effects of neurofeedback on the dysregulation profile in children with ADHD: SCP NF meets SDQ-DP - a retrospective analysis.

BACKGROUND: As children with attention-deficit/hyperactivity disorder (ADHD) usually show psychopathological signs beyond their core symptoms (e.g. elevated scores of the dysregulation profile (DP) in 30-40%), treatments with a broader approach to self-regulation skills may be supportive. Neurofeedback (NF) may reflect such an option. Aim of the present analysis was to compare the effects of slow cortical potential (SCP) NF and θ/ß NF on the DP using data from a previous trial. METHODS: Thirty children with ADHD (aged 8-12 years) and a DP score in the Strengths and Difficulties Questionnaire (SDQ-DP) ⩾ 3 were included. NF treatment consisted of one block of SCP NF and one block of θ/ß NF (18 units per block) allowing an intraindividual comparison. Effects of the NF protocols were also contrasted to a control group (n = 18) that completed an attention skills training (between-group analysis). RESULTS: Regarding the SDQ-DP, SCP NF was superior to θ/ß NF and the control condition. Effects of SCP NF and θ/ß NF on ADHD symptom severity were not significantly different. The SDQ-DP score did not correlate with EEG-related measures previously found to be predictors for SCP NF on ADHD symptoms. CONCLUSIONS: SCP NF may reflect a more general approach to improve cognitive, emotional and behavioral self-regulation skills. If confirmed in a larger sample, the SDQ-DP score could be used as an indication criterion and contribute to the individualization of NF in ADHD. Overall, the differential effect provides further evidence for the specificity of NF effects.

Chronic fluoxetine treatment changes S100B expression during postnatal rat brain development.

BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, is approved for treatment of childhood depression. In rats, fluoxetine influences neuronal development, but it is unclear whether it also influences glia development. S100B is a glia-derived calcium-binding protein, which may influence the development of serotonergic fibers and, vice versa, serotonin may influence the expression of S100B. OBJECTIVES: The purpose of this study was to investigate whether fluoxetine treatment influences the expression of S100B during postnatal development, and whether potential changes are regionally dependent upon the time frame of drug administration. METHODS: S100B gene expression and S100B protein expression in three different brain regions (frontal cortex, hippocampus, and striatum) were studied by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. First, a short-term effect, 24 hours after a 14 day fluoxetine treatment (5 mg/kg/bw s.c.) of rats either from postnatal day (PD) 1 to 15, 21 to 35, or 50 to 64, was investigated. Then, the same treatment was used to analyze S100B gene and protein levels at PD 90 (long-term effect). RESULTS: At PD 90, a significant increase of gene and protein expression was observed in all regions if rats were treated during PDs 21-35, whereas treatment during other periods had no long-term effects. A short-term effect 24 hours after fluoxetine treatment was found for almost all development stages and regions, demonstrated by a significant increase of S100B. CONCLUSIONS: These results support recent research indicating a highly drug-sensitive period (i.e., periadolescence) of rat brain development. Therefore, further clinical studies should be performed to clarify whether such a sensitive period also exists in children.