Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy

Purpose: The design, conduct and completion of randomized trials for curative prostate cancer (PCa) treatments are challenging. To evaluate the effect of robot-assisted radical prostatectomy (RARP) versus focal irreversible electroporation (IRE) on patient-reported quality of life (QoL) and early oncological control using propensity-scored matching. Methods: Patients with T1c–cT2b significant PCa (hig

Numerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue in vivo with IRE. Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy. In 13 patients, numerical models of the electrical field were generated and compared with the ablation zone volume on whole-mount pathology and T2-weighted magnetic resonance imaging (MRI) sequences. Volume-generating software was used to calculate the ablation zone volumes on histology and MRI. The electric field threshold to ablate prostate tissue was determined for each patient. Results: A total of 13 patients were included for histological and simulation analysis. The median electrical field threshold was 550 V/cm (interquartile range 383-750 V/cm) for the software-generated histology volumes. The median electrical field threshold was 500 V/cm (interquartile range 386-580 V/cm) when the ablation zone volumes were used from the follow-up MRI. Conclusions: The electrical field threshold to ablate human prostate tissue in vivo was determined using whole-mount pathology and MRI. These thresholds may be used to develop treatment planning or monitoring software for IRE prostate ablation; however, further optimization of simulation methods are required to decrease the variance that was observed between patients

MRI and CT in the follow-up after irreversible electroporation of small renal masses

PURPOSE Ablation plays a growing role in the treatment of small renal masses (SRMs) due to its nephron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the potential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow-up after renal IRE in humans. Objectives are to assess the use of computed tomography (CT) and magnetic resonance imaging (MRI) to determine the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE. METHODS This was a prospective phase 2 study of IRE in 9 patients with 10 SRMs. MRI was performed pre-IRE, 1 week, 3 months, 6 months, and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months, and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and their relation with the needle configuration volume (NCV; indicating planned AZV) were evaluated based on CT and MRI measurements. RESULTS Eight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a nondiagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (16.8 cm(3) and 6.2 cm(3), respectively) compared with the NCV (4.8 cm(3)). On MRI, median AZV increased 1 week post-IRE until 3 months post-IRE (14.5 cm(3) and 4.6 cm(3), respectively) compared with the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm(3); MRI 3.0 cm(3)), continuing at 12 months (CT 4.2 cm(3), MRI 1.1 cm(3)). Strong correlation was demonstrated between the planned and the post-treatment volumes. Inter-observer agreement was excellent (CT: 95% CI 0.82-0.95; MRI: 95% CI 0.86-0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumor. Subtraction images confirmed non-enhancement on MRI in cases with unclear enhancement (3/9). Directly after IRE, gas bubbles, perinephric stranding, and edema were observed in all cases. CONCLUSION Both CT and MRI findings indicate increase of AZV until 3 months post-IRE, followed by gradual decrease in AZV from 6 to 12 months post-IRE. Enhancement is absent in cases with complete ablation. Gas bubbles, perinephric stranding, and edema are normal findings directly post-IRE.Netherlands Organization for Health Research and Developmen

Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?

Objective: To provide a summary and discussion of international guidelines, position statements and consensus statements in relation to focal therapy (FT) for prostate cancer (PCa). Methods: The European Association of Urology-European Association of Nuclear Medicine-European Society for Radiotherapy and Oncology-European Society of Urogential Radiology-International Society of Urological Pathology-International Society of Geriatric Oncology and American Urological Association-American Society for Radiation Oncology-Society of Urologic Oncology guidelines were interrogated for recommendations for FT. PubMed and Ovid Medline were searched for consensus statements. Only studies in English since 2015 were included. Reference lists of the included articles were also interrogated and a manual search for studies was also performed. Results: Our results showed a lack of long-term randomised data for FT. International Urological guidelines emphasised the need for more high-quality clinical trials with robust oncological and toxicity outcomes. Consensus and positions statements were heterogenous. Conclusion: A globally accepted guideline for FT planning, technique and follow-up are still yet to be determined. Well-designed studies with long-term follow-up and robust clinical and toxicity endpoints are needed to improve our understanding of FT and create uniform guidelines to streamline management and follow-up

Superior Biochemical Recurrence and Long-term Quality-of-life Outcomes Are Achievable with Robotic Radical Prostatectomy After a Long Learning Curve-Updated Analysis of a Prospective Single-surgeon Cohort of 2206 Consecutive Cases

Our earlier analysis suggested that robot-assisted radical prostatectomy (RARP) achieved superiority over open radical prostatectomy (ORP) in terms of positive surgical margin (PSM) rates and functional outcomes. With larger sample size and longer follow-up, the objective of this study update is to assess whether our previous findings are upheld and whether the improved PSM rates for RARP after an initial learning curve compared with ORP-as observed in our earlier analysis-ultimately resulted in improved biochemical control. Prospective observational study comparing two surgical techniques; 2271 consecutive men underwent RARP (1520) or ORP (751) at a single centre from 2006 to 2016. Demographic and clinicopathological data were prospectively collected. The EPIC-QOL questionnaire was administered at baseline and 1.5, 3, 6, 12, and 24 mo. Multivariate linear regression modelled the difference in quality of life (QOL) domains against case number; logistic and Cox regression modelled the differences in PSM and biochemical recurrence (BCR) hazard ratios (HR), respectively. A total of 2206 men were included in BCR/PSM analysis and 1045 consented for QOL analysis. Superior pT2 surgical margins, early and late sexual outcomes, and early urinary outcomes were upheld and became more robust (narrowing of 95% confidence intervals [CIs]). The risk of BCR was initially higher for RARP, improved after 191 RARPs, and was 35% lower (hazard ratio [HR] 0.65, 95% CI 0.47-0.90) at final RARP, plateauing after 226 RARPs. Improved late (12-24 mo) urinary bother scores (adjusted mean difference [AMD]=4.7, 95% CI 1.3-8.0) and irritative-obstructive scores (AMD=3.8, 95% CI 0.9-5.6) at final RARP were demonstrated. Limitations include observational single surgeon data, possible residual confounding, and short follow-up. The results from this updated analysis demonstrate that RARP can be beneficial for patients of high-volume surgeons, although more randomised studies and studies with survival outcomes are needed. Robot-assisted radical prostatectomy was able to improve functional and oncological outcomes in this single surgeon's learning curv

Clinical relevance of the bile acid receptor TGR5 in metabolism

The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus on the translation of preclinical studies into clinically applicable findings. Studies in rodents suggest an important role for Tgr5 in Glp-1 secretion, insulin sensitivity, and energy expenditure. However, evidence of effects on these processes from human studies is less convincing. Ultimately, safe and selective human TGR5 agonists are needed to test the therapeutic potential of TGR

Confocal laser endomicroscopy and optical coherence tomography for the diagnosis of prostate cancer: A needle-based, in vivo feasibility study protocol (Ideal phase 2a)

WOS: 000433883200033PubMed ID: 29784633Background: Focal therapy for prostate cancer has been proposed as an alternative treatment to whole-gland therapies in selected men to diminish side effects in localized prostate cancer. As nowadays imaging cannot offer complete prostate cancer disease characterization, multicore systematic biopsies are recommended (transrectal or transperineal). Optical imaging techniques such as confocal laser endomicroscopy and optical coherence tomography allow in vivo, high-resolution imaging. Moreover, they can provide real-time visualization and analysis of tissue and have the potential to offer additive diagnostic information. Objective: This study has 2 separate primary objectives. The first is to assess the technical feasibility and safety of in vivo focal imaging with confocal laser endomicroscopy and optical coherence tomography. The second is to identify and define characteristics of prostate cancer and normal prostate tissue in confocal laser endomicroscopy and optical coherence tomography imaging by comparing these images with the corresponding histopathology. Methods: In this prospective, in vivo feasibility study, needle-based confocal laser endomicroscopy and optical coherence tomography imaging will be performed before transperineal template mapping biopsy or radical prostatectomy. First, confocal laser endomicroscopy and optical coherence tomography will be performed in 4 patients (2 for each imaging modality) undergoing transperineal template mapping biopsy to assess the feasibility and safety of confocal laser endomicroscopy and optical coherence tomography. If proven to be safe and feasible, confocal laser endomicroscopy and optical coherence tomography will be performed in 10 patients (5 for each imaging modality) undergoing radical prostatectomy. Confocal laser endomicroscopy and optical coherence tomography images will be analyzed by independent, blinded observers. Confocal laser endomicroscopy-and optical coherence tomography-based qualitative and quantitative characteristics and histopathology will be compared. The study complies with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) stage2a recommendations. Results: At present, the study is enrolling patients and results and outcomes are expected in 2019. Conclusions: Confocal laser endomicroscopy and optical coherence tomography are promising optical imaging techniques that can visualize and analyze tissue structure, possible tumor grade, and architecture in real time. They can potentially provide real-time, high-resolution microscopic imaging and tissue characteristics of prostate cancer in conjunction with magnetic resonance imaging or transrectal ultrasound fusion-guided biopsy procedures. This study will provide insight into the feasibility and tissue-specific characteristics of confocal laser endomicroscopy and optical coherence tomography for real-time optical analysis of prostate cancer.STWFunding for this trial was obtained within STW. The funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results

MRI and CT in the follow-up after irreversible electroporation of small renal masses

PURPOSE Ablation plays a growing role in the treatment of small renal masses (SRMs) due to its neph-ron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the po-tential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow-up after renal IRE in humans. Objectives are to assess the use of computed tomography (CT) and magnetic resonance imaging (MRI) to determine the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE. METHODS This was a prospective phase 2 study of IRE in 9 patients with 10 SRMs. MRI was performed pre-IRE, 1 week, 3 months, 6 months, and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months, and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and their relation with the needle configuration volume (NCV; indicating planned AZV) were evaluated based on CT and MRI measurements. RESULTS Eight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a nondiagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (16.8 cm3 and 6.2 cm3, respectively) compared with the NCV (4.8 cm3). On MRI, median AZV increased 1 week post-IRE until 3 months post-IRE (14.5 cm3 and 4.6 cm3, respectively) compared with the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm3; MRI 3.0 cm3), continuing at 12 months (CT 4.2 cm3, MRI 1.1 cm3). Strong correlation was demonstrated between the planned and the post-treatment volumes. Inter-observer agreement was excellent (CT: 95% CI 0.82–0.95; MRI: 95% CI 0.86–0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumor. Subtraction images confirmed non-enhancement on MRI in cases with unclear enhancement (3/9). Directly after IRE, gas bubbles, perinephric stranding, and edema were observed in all cases. CONCLUSION Both CT and MRI findings indicate increase of AZV until 3 months post-IRE, followed by grad-ual decrease in AZV from 6 to 12 months post-IRE. Enhancement is absent in cases with com-plete ablation. Gas bubbles, perinephric stranding, and edema are normal findings directly post-IRE