Transperineal laser ablation as treatment for benign prostatic obstruction: Safety, feasibility and functional outcomes-A pilot study.

Background: Standard surgical treatment for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) requires anaesthesia and hospitalization. Transperineal laser ablation (TPLA) is a novel minimally invasive treatment for BPO, which has been performed using local anaesthetics and conscious sedation. Objectives: The aim of this study is to assess safety, feasibility and functional outcomes of TPLA for the treatment of LUTS in men fit also for standard surgery. Methods: This prospective, multicentre, interventional pilot study included 20 patients. Eligible patients were men ≥40 years of age, with urodynamically proven bladder outlet obstruction, a peak urinary flow of 5-15 mL/s and a prostate volume of 30-120 cc. All subjects underwent Soractelite™ TPLA using the Echolaser® X4 system. Two to four fibres were placed in the prostate, whereafter laser light induced coagulative necrosis. Twelve months of follow-up included uroflowmetry, an ultrasound of the prostate and PROMs (IPSS and IIEF). Results: Twenty patients were treated with TPLA using local anaesthetics and optional sedation. Sixteen patients were treated in an outpatient setting, using only local anaesthetics in 12 of them; four were treated in the operating room, whereof two under general anaesthesia. No device related adverse events occurred, nor did any grade ≥3 adverse events during follow-up. Post-TPLA, 10 men continued spontaneous voiding, and 10 men developed a urinary retention treated by a temporary indwelling catheter for 15.2 ± 3.5 days. At 12 months, Qmax improved from 9.7 ± 3.5 to 14.9 ± 6.0 (p = 0.015), IPSS improved from 21.3 ± 5.2 to 10.9 ± 5.5 (p < 0.0001), QoL improved from 4.9 ± 0.9 to 1.9 ± 1.1 (p < 0.0001), IIEF-15 total score remained stable and 11/13 patients (85%) preserved antegrade ejaculation. Conclusions: TPLA is a safe and feasible treatment for men with LUTS due to BPO. TPLA can be performed in an outpatient setting under only local anaesthetics. Functional and quality of life outcomes improved significantly at 12 months, and erectile function remained stable.

Using prostate-specific membrane antigen positron-emission tomography to guide prostate biopsies and stage men at high-risk of prostate cancer.

OBJECTIVE: To assess whether a diagnostic pathway in which prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is used as a single imaging modality is feasible to guide targeted biopsy and to detect clinically significant prostate cancer (csPCa) in biopsy-naïve men at high-risk of disease. PATIENTS AND METHODS: A total of 60 men with a prostate-specific antigen (PSA) level of 20-50 ng/mL underwent 18 F-PSMA(DCFPyL)-PET/CT prior to prostate biopsies in this prospective, non-randomised cohort study. Magnetic resonance imaging (MRI) was not performed. Using a 12-segment mapping model of the prostate, PSMA-guided targeted biopsy was performed along with systematic biopsies. The detection rate of PCa and csPCa was assessed for combined systematic and targeted biopsy, and for targeted biopsy only. csPCa was defined as a prostate biopsy with an International Society of Uropathology (ISUP) Grade Group ≥2. RESULTS: Lesions suspicious for PCa in the prostate gland were observed on all PSMA-PET/CTs. A total of 27/60 men (45%) already had metastatic disease on staging 18 F-PSMA(DCFPyL)-PET/CT. Combined PSMA-guided targeted and systematic biopsies detected PCa in 56/60 (93.3%) patients, with 52 of them (92.9%) having csPCa. PSMA-guided targeted biopsy, if performed as a single biopsy modality, identified PCa in 52/60 men (86.7%) and in 27/27 men (100%) men with metastases. CONCLUSIONS: Using the PSMA-driven single imaging modality pathway in biopsy-naïve men at high-risk of PCa, a substantial number of diagnostic MRI scans could be avoided while at the same time obtaining adequate targeting, staging, and detection of csPCa.

Reliable Visualization of the Treatment Effect of Transperineal Focal Laser Ablation in Prostate Cancer Patients by Magnetic Resonance Imaging and Contrast-enhanced Ultrasound Imaging.

Background: Transperineal focal laser ablation (TPLA) treatment for prostate cancer (PCa) is an experimental focal ablative therapy modality with low morbidity. However, a dosimetry model for TPLA is lacking. Objective: To determine (1) the three-dimensional (3D) histologically defined ablation zone of single- and multifiber TPLA treatment for PCa correlated with magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) and (2) a reliable imaging modality of ablation zone volumetry. Design setting and participants: This was a prospective, multicenter, and interventional phase I/II pilot study with an ablate-and-resect design. TPLA was performed in 12 patients with localized prostate cancer divided over four treatment regimens to evaluate potential variation in outcomes. Intervention: TPLA was performed approximately 4 wk prior to robot-assisted radical prostatectomy (RARP) in a daycare setting using local anesthesia. Outcome measurements and statistical analysis: Four weeks after TPLA, ablation zone volumetry was determined on prostate MRI and CEUS by delineation and segmentation into 3D models and correlated with whole-mount RARP histology using the Pearson correlation index. Results and limitations: Twelve office-based TPLA procedures were performed successfully under continuous transrectal ultrasound guidance using local perineal anesthesia. No serious adverse events occurred. A qualitative analysis showed a clear demarcation of the ablation zone on T2-weighted MRI, dynamic contrast-enhanced MRI, and CEUS. On pathological evaluation, no remnant cancer was observed within the ablation zone. Ablation zone volumetry on CEUS and T2-weighted MRI compared with histology had a Pearson correlation index of r = 0.94 (95% confidence interval [CI] 0.74-0.99, p < 0.001) and r = 0.93 (95% CI 0.73-0.98, p < 0.001), respectively. Conclusions: CEUS and prostate MRI could reliably visualize TPLA ablative effects after minimally invasive PCa treatment with a high concordance with histopathological findings and showed no remnant cancer. Patient summary: The treatment effects of a novel minimally invasive ablation therapy device can reliably be visualized with radiological examinations. These results will improve planning and performance of future procedures.

Novel minimally invasive treatments for lower urinary tract symptoms: a systematic review and network meta-analysis

ABSTRACT Purpose: To review and compare the effectivity of novel minimally invasive treatments (MITs) to transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) in men. Methods: Medline, Embase, and Cochrane databases were searched from January 2010 to December 2022 for randomized controlled trials (RCTs) evaluating MITs, compared to TURP or sham, in men with LUTS. Studies were assessed by risk of bias tool, and evidence by GRADE. Functional outcomes by means of uroflowmetry and IPSS were the primary outcomes, safety and sexual function were secondary outcomes. As part of this review, a network meta-analysis (NMA) was conducted. MITs were ranked based on functional outcome improvement probability. Results: In total, 10 RCTs were included, evaluating aquablation, prostatic urethral lift, prostatic artery embolization (PAE), convective water vapor thermal treatment or temporary implantable nitinol device. All MITs showed a better safety profile compared to TURP. Functional outcome improvement following aquablation were comparable to TURP. In the NMA, aquablation was ranked highest, PAE followed with the second highest probability to improve functional outcomes. Other novel MITs resulted in worse functional outcomes compared to TURP. Level of evidence was low to very low. Conclusions: Five MITs for treatment of LUTS were identified. Aquablation is likely to result in functional outcomes most comparable to TURP. Second in ranking was PAE, a technique that does not require general or spinal anesthesia. MITs have a better safety profile compared to TURP. However, due to high study heterogeneity, results should be interpreted with caution.

Novel minimally invasive treatments for lower urinary tract symptoms: a systematic review and network meta-analysis.

PURPOSE: To review and compare the effectivity of novel minimally invasive treatments (MITs) to transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) in men. METHODS: Medline, Embase, and Cochrane databases were searched from January 2010 to December 2022 for randomized controlled trials (RCTs) evaluating MITs, compared to TURP or sham, in men with LUTS. Studies were assessed by risk of bias tool, and evidence by GRADE. Functional outcomes by means of uroflowmetry and IPSS were the primary outcomes, safety and sexual function were secondary outcomes. As part of this review, a network meta-analysis (NMA) was conducted. MITs were ranked based on functional outcome improvement probability. RESULTS: In total, 10 RCTs were included, evaluating aquablation, prostatic urethral lift, prostatic artery embolization (PAE), convective water vapor thermal treatment or temporary implantable nitinol device. All MITs showed a better safety profile compared to TURP. Functional outcome improvement following aquablation were comparable to TURP. In the NMA, aquablation was ranked highest, PAE followed with the second highest probability to improve functional outcomes. Other novel MITs resulted in worse functional outcomes compared to TURP. Level of evidence was low to very low. CONCLUSIONS: Five MITs for treatment of LUTS were identified. Aquablation is likely to result in functional outcomes most comparable to TURP. Second in ranking was PAE, a technique that does not require general or spinal anesthesia. MITs have a better safety profile compared to TURP. However, due to high study heterogeneity, results should be interpreted with caution.

An optimized prostate biopsy strategy in patients with a unilateral lesion on prostate magnetic resonance imaging avoids unnecessary biopsies.

Purpose: The introduction of magnetic resonance imaging (MRI)-targeted biopsy (TBx) besides systematic prostate biopsies has resulted in a discussion on what the optimal prostate biopsy strategy is. The ideal template has high sensitivity for clinically significant prostate cancer (csPCa), while reducing the detection rate of clinically insignificant prostate cancer (iPCa). This study evaluates different biopsy strategies in patients with a unilateral prostate MRI lesion. Methods: Retrospective subgroup analysis of a prospectively managed database consisting of patients undergoing prostate biopsy in two academic centres. Patients with a unilateral lesion (PI-RADS ⩾ 3) on MRI were included for analysis. The primary objective was to evaluate the diagnostic performance for different biopsy approaches compared with bilateral systematic prostate biopsy (SBx) and TBx. Detection rates for csPCa (ISUP ⩾ 2), adjusted csPCa (ISUP ⩾ 3) and iPCa (ISUP = 1) were determined for SBx alone, TBx alone, contralateral SBx combined with TBx and ipsilateral SBx combined with TBx. A subgroup analysis was performed for biopsy-naive patients. Results: A total of 228 patients were included from October 2015 to September 2021. Prostate cancer (PCa) detection rate of combined SBx and TBx was 63.5% for csPCa, 35.5% for adjusted csPCa, and 14% for iPCa. The best performing alternative biopsy strategy was TBx and ipsilateral SBx, which reached a sensitivity of 98.6% (95% CI: 95.1-99.6) for csPCa and 98.8% (95% CI: 96.3-99.9) for adjusted csPCa, missing only 1.4% of csPCa, while reducing iPCa detection by 15.6% compared with SBx and TBx. TBx or SBx alone missed a significant amount of csPCa, with sensitivities of 90.3% (95% CI: 84.4-94.2) and 86.8% (95% CI: 80.4-91.4) for csPCa. Subgroup analysis on biopsy-naive patients showed similar results as the overall group. Conclusion: This study shows that performing TBx with ipsilateral SBx and omitting contralateral SBx is the optimal biopsy strategy in patients with a unilateral MRI lesion. With this strategy, a very limited amount of csPCa is missed and iPCa detection is reduced.

Image-guided in-Vivo Needle-Based Confocal Laser Endomicroscopy in the Prostate: Safety and Feasibility Study in 2 Patients.

Purpose: To assess the safety and technical feasibility of in-vivo needle-based forward-looking confocal laser endomicroscopy in prostate tissue. Methods: For this feasibility study, 2 patients with a suspicion of prostate cancer underwent transperineal needle-based confocal laser endomicroscopy during ultrasound-guided transperineal template mapping biopsies. After intravenous administration of fluorescein, needle-based confocal laser endomicroscopy imaging was performed with a forward-looking probe (outer diameter 0.9 mm) in 2 trajectories during a manual push-forward and pullback motion. A biopsy was taken in a coregistered parallel adjacent trajectory to the confocal laser endomicroscopy trajectory for histopathologic comparison. Peri- and postprocedural adverse events, confocal laser endomicroscopy device malfunction and procedural failures were recorded. Needle-based confocal laser endomicroscopy image quality assessment, image interpretation, and histology were performed by an experienced confocal laser endomicroscopy rater and uro-pathologist, blinded to any additional information. Results: In both patients, no peri- and post-procedural adverse events were reported following needle-based confocal laser endomicroscopy. No confocal laser endomicroscopy device malfunction nor procedural failures were reported. Within 1.5 min after intravenous administration of fluorescein, needle-based confocal laser endomicroscopy image quality was sufficient for interpretation for at least 14 min, yielding more than 5000 confocal laser endomicroscopy frames per patient. The pullback confocal laser endomicroscopy recordings and most of the push-forward recordings almost only visualized erythrocytes, being classified as non-representative. During the push-forward recordings, prostate tissue was occasionally visualized in single frames, insufficient for histopathologic comparison. Prostate carcinoma was identified by biopsy in one patient (Gleason score 4 + 3 = 7, >50%), while the biopsy from the other patient showed no malignancy. Conclusion: Needle-based confocal laser endomicroscopy imaging of in-vivo prostate tissue with a forward-looking confocal laser endomicroscopy probe is safe without device malfunctions or procedural failures. Needle-based confocal laser endomicroscopy is technically feasible, but the acquired confocal laser endomicroscopy datasets are non-representative. The confocal laser endomicroscopy images' non-representative nature is possibly caused by bleeding artifacts, movement artifacts and a lack of contact time with the tissue of interest. A different confocal laser endomicroscopy probe or procedure might yield representative images of prostatic tissue.

Safety and Feasibility of Soractelite Transperineal Focal Laser Ablation for Prostate Cancer and Short-term Quality of Life Analysis from a Multicenter Pilot Study.

Background: Soractelite™ transperineal focal laser ablation (TPLA) for the treatment of localized prostate cancer (PCa) using the Echolaser® system is a novel minimally invasive technique that has the potential to induce tissue ablation, while reducing treatment-related morbidity, when compared with robot-assisted radical prostatectomy (RARP) and radiotherapy. Objective: To determine the short-term safety and feasibility of single or multifiber TPLA, its functional outcomes, and quality of life (QoL). Design setting and participants: TPLA was performed in 12 patients, consecutively assigned to four treatment regimens, with localized PCa who were scheduled for RARP ("ablate and resect design"). The treatment regimens were as follows: (1) a single fiber at 3 W, (2) two fibers at 5 mm distance at 3 W, (3) two fibers at 10 mm distance at 3 W, and (4) a single fiber at 5 W. TPLA was scheduled 4 wk prior to RARP. Intervention: TPLA using the Echolaser® system under local anesthesia at the outpatient clinic. Outcome measurements and statistical analysis: Safety and feasibility were determined by the assessment of device-related peri- and postoperative adverse events (AEs), and length of hospital stay. Functional outcomes and QoL were measured using validated questionnaires. Feasibility of RARP was assessed by a questionnaire for the urologist. Results and limitations: Patients were dismissed after a median (interquartile range) hospital admission of 3.25 (1.25) h. No device-related AEs occurred. AEs that occurred were mostly related to lower urinary tract symptoms and were mild (grade 1-2). Most AEs resolved within 1 wk. A QoL analysis showed no significant differences for all treatment regimens. Functional outcomes remained unchanged, except for erectile function after 1 wk, which returned to baseline after 4 wk. TPLA treatment did not compromise RARP, based on the questionnaires. Conclusions: TPLA for the treatment of PCa at the outpatient clinic appears to be safe and feasible with good short-term QoL and functional outcomes; oncological results are awaited. Patient summary: Focal treatment of localized prostate cancer can safely be performed in a daycare setting using a new technique, based on laser ablation, without compromising quality of life.

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Detect Residual Prostate Cancer Following Irreversible Electroporation-A Multicenter Validation Study.

BACKGROUND: Accurate monitoring following focal treatment of prostate cancer (PCa) is paramount for timely salvage treatment or retreatment. OBJECTIVE: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) to detect residual PCa in the short-term follow-up of focal treatment with irreversible electroporation (IRE) using transperineal or transrectal template ± targeted biopsies. DESIGN, SETTING, AND PARTICIPANTS: A retrospective international multicenter study of men with biopsy-proven PCa, treated with focal IRE, and followed by mpMRI (index-test) and template biopsies (reference-test) between February 2013 and January 2021, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI were calculated for in- and outfield residual disease based on two definitions of significant PCa: University College London (UCL) 1-International Society of Urological Pathology (ISUP) ≥3 or ISUP ≥1 with maximum cancer core length (MCCL) ≥6 mm, and UCL2-ISUP ≥2 or ISUP ≥1 with MCCL ≥4 mm. RESULTS AND LIMITATIONS: A total of 303 patients from five focal therapy centers were treated with primary IRE. The final analysis was performed on 217 men (median age 67, median prostate-specific antigen 6.2, 81% ISUP 2/3) who underwent both mpMRI and template biopsies. Multiparametric MRI missed 38/57 (67%) positive biopsy locations (UCL1) in 22 patients. Sensitivity, specificity, PPV, and NPV of mpMRI to detect whole gland residual disease (UCL1) were 43.6% (95% confidence interval [CI]: 28-59), 80.9% (95% CI: 75-86), 33.3% (95% CI: 21-47), and 86.7% (95% CI: 81-91), respectively. Based on UCL2, sensitivity, specificity, PPV, and NPV were 35.8% (95% CI: 25-48), 82.0% (95% CI: 75-88), 47.1% (95% CI: 34-61), and 74.1% (95% CI: 67-80), respectively. Limitations are the retrospective nature and short follow-up. CONCLUSIONS: The diagnostic accuracy of mpMRI to detect residual clinically significant PCa following IRE was low. Follow-up template biopsies should be performed, regardless of mpMRI results. PATIENT SUMMARY: We investigated the accuracy of magnetic resonance imaging (MRI) to detect residual prostate cancer after treatment with irreversible electroporation. The accuracy of MRI is insufficient, and we emphasize the importance of confirmatory prostate biopsies.

Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer.

OBJECTIVE: To evaluate: (i) safety, (ii) feasibility, and medium-term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE). PATIENTS AND METHODS: An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life. RESULTS: In four participating centres, a total of 39 patients with a median (interquartile range [IQR]) age 64 (60-67) years were identified. No serious adverse events occurred during or following sRP and surgery was deemed feasible without difficulties. The median (IQR) time to recurrence following IRE was 14.3 (9.1-38.8) months. Pathology results showed localised disease in 21 patients (53.8%) and locally-advanced disease in 18 (46.2%). Positive surgical margins (PSMs) were observed in 10 patients (25.6%), of which six (15.4%) had significant PSMs. A persistent detectable prostate-specific antigen level was found in one case after sRP, caused by metastatic disease. One patient had a biochemical recurrence 6 months after sRP. These two cases, together with a PSM case, required additional therapy after sRP. After a median (IQR) follow-up of 17.7 (11.8-26.4) months, urinary continence and erectile function were preserved in 34 (94.4%) and 18 patients (52.9%), respectively, while quality of life remained stable. CONCLUSIONS: Salvage RP is safe and feasible for patients with recurrent localised PCa following initial IRE treatment. The medium-term oncological and functional outcomes are similar to primary RP. Strict patient selection for focal therapy and standardised follow-up is needed as some patients developed high-grade disease.

Predictors of clinically significant prostate cancer in biopsy-naïve and prior negative biopsy men with a negative prostate MRI: improving MRI-based screening with a novel risk calculator.

Purpose: A pre-biopsy decision aid is needed to counsel men with a clinical suspicion for clinically significant prostate cancer (csPCa), despite normal prostate magnetic resonance imaging (MRI). Methods: A risk calculator (RC) for csPCa (International Society of Urological Pathology grade group (ISUP) ⩾ 2) presence in men with a negative-MRI (Prostate Imaging-Reporting and Data System (PI-RADS) ⩽ 2) was developed, and its performance was compared with RCs of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Prostate Biopsy Collaborative Group (PBCG), and Prospective Loyola University mpMRI (PLUM). All biopsy-naïve and prior negative biopsy men with a negative-MRI followed by systematic prostate biopsy were included from October 2015 to September 2021. The RC was developed using multivariable logistic regression with the following parameters: age (years), family history of PCa (first- or second-degree family member), ancestry (African Caribbean/other), digital rectal exam (benign/malignant), MRI field strength (1.5/3.0 Tesla), prior negative biopsy status, and prostate-specific antigen (PSA) density (ng/ml/cc). Performance of RCs was compared using receiver operating characteristic (ROC) curve analysis. Results: A total of 232 men were included for analysis, of which 18.1% had csPCa. Parameters associated with csPCa were family history of PCa (p < 0.0001), African Caribbean ancestry (p = 0.005), PSA density (p = 0.002), prior negative biopsy (p = 0.06), and age at biopsy (p = 0.157). The area under the curve (AUC) of the developed RC was 0.76 (95% CI 0.68-0.85). This was significantly better than the RCs of the ERSPC (AUC: 0.59; p = 0.001) and PBCG (AUC: 0.60; p = 0.002), yet similar to PLUM (AUC: 0.69; p = 0.09). Conclusion: The developed RC (Prostate Biopsy Cohort Amsterdam ('PROBA' RC), integrated predictors for csPCa at prostate biopsy in negative-MRI men and outperformed other widely used RCs. These findings require external validation before introduction in daily practice.

Focal therapy for localized cancer: a patent review.

INTRODUCTION: Conventional cancer treatments such as radical surgery and systemic therapy targeting the organ or organ system might have side effects because of damage to the surrounding tissue. For this reason, there is a need for new instruments that focally treat cancer. AREAS COVERED: This review provides a comprehensive overview of the patent literature on minimally and noninvasive focal therapy instruments to treat localized cancer. The medical section of the Google Patents database was scanned, and 128 patents on focal therapy instruments published in the last two decades (2000-2021) were retrieved and classified. The classification is based on the treatment target (cancer cell or network of cancer cells), treatment purpose (destroy the cancerous structure or disable its function), and treatment means (energy, matter, or a combination of both). EXPERT OPINION: We found patents describing instruments for all groups, except for the instruments that destroy a cancer cell network structure by applying matter (e.g. particles) to the network. The description of the different treatment types may serve as a source of inspiration for new focal therapy instruments to treat localized cancer.

Transperineal Laser Ablation Treatment for Lower Urinary Tract Symptoms Due to Benign Prostatic Obstruction: Protocol for a Prospective In Vivo Pilot Study.

BACKGROUND: Standard surgical treatments for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) use a transurethral approach. Drawbacks are the need for general or spinal anesthesia and complications such as hematuria, strictures, and cloth retention. Therefore, a minimal invasive technique under local anesthesia is desired to improve patient safety. Recently, SoracteLite transperineal laser ablation (TPLA) has been introduced as a novel minimal invasive treatment for BPO. The system used is unique because 4 laser sources are independently available. This 1064-nm diode laser induces coagulative necrosis. Moreover, TPLA is unique because it has a transperineal approach and can be performed under local anesthesia in an outpatient setting. OBJECTIVE: The primary objective of this study is to determine the safety and feasibility of TPLA treatment for men, who are fit for standard surgery, with LUTS due to BPO. The secondary objectives are to determine functional outcomes by flowmetry and patient-reported outcome measures (PROMs), side effects, and tissue changes observed on imaging. METHODS: This study is a prospective, single center, interventional pilot study IDEAL framework stage 2a and will include 20 patients. Eligible patients are men ≥40 years of age, with a prostate volume of 30 to 120 cc, have urodynamically proven bladder outlet obstruction, and have a peak urinary flow of 5 to 15 mL per second. All patients will undergo TPLA of their prostate under local anesthesia by using the EchoLaser system. Depending on the prostate volume, 2 to 4 laser fibers will be placed bilaterally into the prostate. Patient follow-up consists of uroflowmetry, PROMs, and imaging by using contrast-enhanced ultrasound. Total follow-up is 12 months following treatment. RESULTS: Presently, recruitment of patients is ongoing. Publication of first results is expected by early 2020. CONCLUSIONS: TPLA offers the potential to be a novel minimal invasive technique for treatment of LUTS due to BPO in men fit for standard desobstruction. This study will evaluate the safety and feasibility of TPLA and report on functional outcomes and tissue changes observed on imaging following TPLA treatment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15687.

Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies.

Many neurodegenerative diseases, such as Huntington's disease, are hallmarked by the formation of intracellular inclusion bodies (IBs) that are decorated with ubiquitin, proteasomes and chaperones. The apparent enrichment of ubiquitin and components involved in protein quality control at IBs suggests local ubiquitin-dependent enzymatic activity. In this study, we examine recruitment of ubiquitin to IBs of polyglutamine-expanded huntingtin fragments (mHtt) by using synthesized TAMRA-labeled ubiquitin moieties. We show that intracellular TAMRA-ubiquitin is dynamic at mHtt IBs and is incorporated into poly-ubiquitin chains of intracellular substrates, such as mHtt, in a conjugation-dependent manner. Furthermore, we report that mHtt IBs recruit catalytically active enzymes involved in (de)-ubiquitination processes based on novel activity-based probes. However, we also find that the overexpression of the GFP-ubiquitin reporter, unlike the endogenous ubiquitin and TAMRA-ubiquitin, becomes irreversibly sequestered as a ring-like structure around the mHtt IBs, suggesting a methodical disadvantage of GFP-tagged ubiquitin. Our data provide supportive evidence for dynamic recruitment of ubiquitin and ubiquitin (de)-conjugating activity at mHtt initiated IBs.

Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome.

Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5 cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS, and that microcalcification serves as a marker for aortic disease severity. To address this hypothesis, we analysed MFS patient and mouse aortas. MFS patient aortic tissue showed enhanced microcalcification in areas with extensive elastic lamina fragmentation in the media. A causal relationship between medial injury and microcalcification was revealed by studies in vascular smooth muscle cells (SMCs); elastin peptides were shown to increase the activity of the calcification marker alkaline phosphatase (ALP) and reduce the expression of the calcification inhibitor matrix GLA protein in human SMCs. In murine Fbn1C1039G/+ MFS aortic SMCs, Alpl mRNA and activity were upregulated as compared with wild-type SMCs. The elastin peptide-induced ALP activity was prevented by incubation with lactose or a neuraminidase inhibitor, which inhibit the elastin receptor complex, and a mitogen-activated protein kinase kinase-1/2 inhibitor, indicating downstream involvement of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation. Histological analyses in MFS mice revealed macrocalcification in the aortic root, whereas the ascending aorta contained microcalcification, as identified with the near-infrared fluorescent bisphosphonate probe OsteoSense-800. Significantly, microcalcification correlated strongly with aortic diameter, distensibility, elastin breaks, and phosphorylated ERK1/2. In conclusion, microcalcification co-localizes with aortic elastin degradation in MFS aortas of humans and mice, where elastin-derived peptides induce a calcification process in SMCs via the elastin receptor complex and ERK1/2 activation. We propose microcalcification as a novel imaging marker to monitor local elastin degradation and thus predict aortic events in MFS patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.