Close proximity risk assessment for SARS-CoV-2 infection.

Although the interpersonal distance represents an important parameter affecting the risk of infection due to respiratory viruses, the mechanism of exposure to exhaled droplets remains insufficiently characterized. In this study, an integrated risk assessment is presented for SARS-CoV-2 close proximity exposure between a speaking infectious subject and a susceptible subject. It is based on a three-dimensional transient numerical model for the description of exhaled droplet spread once emitted by a speaking person, coupled with a recently proposed SARS-CoV-2 emission approach. Particle image velocimetry measurements were conducted to validate the numerical model. The contribution of the large droplets to the risk is barely noticeable only for distances well below 0.6 m, whereas it drops to zero for greater distances where it depends only on airborne droplets. In particular, for short exposures (10 s) a minimum safety distance of 0.75 m should be maintained to lower the risk below 0.1%; for exposures of 1 and 15 min this distance increases to about 1.1 and 1.5 m, respectively. Based on the interpersonal distances across countries reported as a function of interacting individuals, cultural differences, and environmental and sociopsychological factors, the approach presented here revealed that, in addition to intimate and personal distances, particular attention must be paid to exposures longer than 1 min within social distances (of about 1 m).

Customized Tool for the Validation of Optical Coherence Tomography in Differentiation of Prostate Cancer.

OBJECTIVE: To design and demonstrate a customized tool to generate histologic sections of the prostate that directly correlate with needle-based optical coherence tomography pullback measurements. MATERIALS AND METHODS: A customized tool was created to hold the prostatectomy specimens during optical coherence tomography measurements and formalin fixation. Using the tool, the prostate could be sliced into slices of 4 mm thickness through the optical coherence tomography measurement trajectory. In this way, whole-mount pathology slides were produced in exactly the same location as the optical coherence tomography measurements were performed. Full 3-dimensional optical coherence tomography pullbacks were fused with the histopathology slides using the 3-dimensional imaging software AMIRA, and images were compared. RESULTS: A radical prostatectomy was performed in a patient (age: 68 years, prostate-specific antigen: 6.0 ng/mL) with Gleason score 3 + 4 = 7 in 2/5 biopsy cores on the left side (15%) and Gleason score 3 + 4 = 7 in 1/5 biopsy cores on the right side (5%). Histopathology after radical prostatectomy showed an anterior located pT2cNx adenocarcinoma (Gleason score 3 + 4 = 7). Histopathological prostate slides were produced using the customized tool for optical coherence tomography measurements, fixation, and slicing of the prostate specimens. These slides correlated exactly with the optical coherence tomography images. Various structures, for example, Gleason 3 + 4 prostate cancer, stroma, healthy glands, and cystic atrophy with septae, could be identified both on optical coherence tomography and on the histopathological prostate slides. CONCLUSION: We successfully designed and applied a customized tool to process radical prostatectomy specimens to improve the coregistration of whole mount histology sections to fresh tissue optical coherence tomography pullback measurements. This technique will be crucial in validating the results of optical coherence tomography imaging studies with histology and can easily be applied in other solid tissues as well, for example, lung, kidney, breast, and liver. This will help improve the efficacy of optical coherence tomography in cancer detection and staging in solid organs.

Surveillance following focal therapy interventions / Seguimiento tras el tratamiento focal en el cáncer de próstata localizado

OBJECTIVE: Focal therapy (FT) is a tissuesparing treatment paradigm for localized prostate cancer (PCa) with the potential to improve functional outcomes while maintaining oncologic safety. This paper aims to provide an overview of important considerations and practical recommendations relating to the follow-up after FT. METHODS: Literature review of papers related to FT in PCa derived from Medline/Pubmed database. Arch. Esp. Urol. 2016; 69 (6): 364-374 364 RESULTS: The recommended minimum follow-up period after FT is 5 years. Standard history taking should include: signs of disease progression, treatment-related complications and psychological aspects. Oncological outcome is based on serial prostate specific antigen monitoring, follow-up imaging (most commonly with multiparametric magnetic resonance imaging) and repeat biopsies (systematic from entire gland or targeted from treated zone). Significant PCa has been found at biopsy in up to 17% of patients after FT. Functional outcomes are evaluated using standardized questionnaires that relate to urinary function, erectile function and quality of life. A systematic review reports urinary continence in 83-100% of patients, erections sufficient for penetration in 54-100%. Outcomes differ between ablative energies and treatment templates. The most common side effects after FT are urinary retention (0-17%), urinary tract infection (UTI) (0-17%) and urinary stricture (0-5%). Rectal fistula is a rare complication occurring in up to 0.1-2% of patients. Clavien-Dindo Grade 3-4 complications are reported in 0-4% of patients. Type and rate vary with treatment modality. Complications should be reported using standardized reporting systems. Most data on FT outcomes come from small heterogeneous trials. Pooling of standardized data is necessary to advance the field of FT. CONCLUSION: Stringent follow-up after FT is required to confirm oncologic safety of the individual patient. Standardized data gathering and data pooling is necessary to evaluate whether FT can live up to its promise of improving functional outcomes while maintaining oncological safety

OBJETIVO: La terapia focal (TF) es una paradigma de tratamiento conservador de tejido para el cáncer de próstata (CaP) localizado con el potencial de mejorar los resultados funcionales manteniendo a la vez la seguridad oncológica. Este artículo tiene como objetivo ofrecer una visión de conjunto de consideraciones importantes y recomendaciones prácticas en relación con el seguimiento después de TF. MÉTODOS: Revisión bibliográfica de los artículos relacionados con TF en CaP derivados de la base de datos Medline/Pubmed. RESULTADOS: El periodo mínimo de seguimiento recomendado después de TF es de 5 años. La historia clínica estándar debe incluir: signos de progresión de la enfermedad, complicaciones relacionada con el tratamiento y aspectos psicológicos. El resultado oncológico se basa en monitorización seriada del PSA, seguimiento con pruebas de imagen (lo más frecuente con RMN multiparamétrica) y biopsias repetidas (sistemáticas de la glándula entera o dirigidas de la zona tratada). El CaP significativo se ha encontrado en la biopsia hasta en el 17% de los pacientes después de TF. Los resultados funcionales se evalúan utilizando cuestionarios estandarizados relacionados con la función urinaria, función eréctil y calidad de vida. Una revisión sistemática comunica continencia urinaria en 83-100% de los pacientes, erección suficiente para la penetración en 54-100%. Los resultados difieren entre las energías ablativas y las plantillas de tratamiento. Los efectos secundarios más frecuentes después de la TF son retención urinaria (0-17%), infección del tracto urinario (ITU) (0-17%) y estenosis urinaria (0-5%). La fistula rectal es una complicación rara que ocurre hasta en 0,1-2% de los pacientes. Las complicaciones grado 3-4 de Clavien- Dindo se reportan en 0,4% de los pacientes. El tipo y la tasa varían con la modalidad de tratamiento. Las complicaciones deberían comunicarse utilizando sistemas de comunicación. La mayoría de los datos de resultados de TF vienen de ensayos clínicos pequeños heterogéneos. Es necesario reunir datos estandarizados para avanzar en el campo de la TF. CONCLUSIONES: Es necesario un seguimiento estricto después de la TF para confirmar la seguridad oncológica del paciente individual. Es necesaria a recogida y reunión de datos estandarizados para evaluar si la TF puede mantener viva su promesa de mejoría de los resultados funcionales a la vez que mantiene la seguridad oncológica

Surveillance following Focal Therapy interventions.

OBJECTIVE: Focal therapy (FT) is a tissuesparing treatment paradigm for localized prostate cancer (PCa) with the potential to improve functional outcomes while maintaining oncologic safety. This paper aims to provide an overview of important considerations and practical recommendations relating to the follow-up after FT. METHODS: Literature review of papers related to FT in PCa derived from Medline/Pubmed database. RESULTS: The recommended minimum follow-up period after FT is 5 years. Standard history taking should include: signs of disease progression, treatment-related complications and psychological aspects. Oncological outcome is based on serial prostate specific antigen monitoring, follow-up imaging (most commonly with multiparametric magnetic resonance imaging) and repeat biopsies (systematic from entire gland or targeted from treated zone). Significant PCa has been found at biopsy in up to 17% of patients after FT. Functional outcomes are evaluated using standardized questionnaires that relate to urinary function, erectile function and quality of life. A systematic review reports urinary continence in 83-100% of patients, erections sufficient for penetration in 54-100%. Outcomes differ between ablative energies and treatment templates. The most common side effects after FT are urinary retention (0-17%), urinary tract infection (UTI) (0-17%) and urinary stricture (0-5%). Rectal fistula is a rare complication occurring in up to 0.1-2% of patients. Clavien-Dindo Grade 3-4 complications are reported in 0-4% of patients. Type and rate vary with treatment modality. Complications should be reported using standardized reporting systems. Most data on FT outcomes come from small heterogeneous trials. Pooling of standardized data is necessary to advance the field of FT. CONCLUSION: Stringent follow-up after FT is required to confirm oncologic safety of the individual patient. Standardized data gathering and data pooling is necessary to evaluate whether FT can live up to its promise of improving functional outcomes while maintaining oncological safety.

Irreversible electroporation, a new modality in Focal Therapy for prostate cancer.

The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols.

Irreversible electoporation, a new modality in focal therapy for prostate cáncer / Electroporación irreversible: una nueva modalidad en Terapia Focal del cáncer de próstata

The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on Arch. Esp. Urol. 2016; 69 (6): 337-344 337 the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols

El uso extensivo de la prueba del antígeno prostático específico (PSA) y la mejoría de las técnicas de imagen han dado como resultado un aumento del diagnóstico del cáncer de próstata. El diagnóstico precoz se acompaña con frecuencia de un número aumentado de tumores localizados (unifocales o unilaterales), de pequeño volumen y bajo grado. La terapia focal es una opción de tratamiento emergente en cáncer de próstata, dirigida a tratar áreas de cáncer individuales conservando importantes estructuras funcionales y anatómicas. La electroporación irreversible es una modalidad de tratamiento innovadora en terapia focal basada en el proceso de electroporación de membrana celular que limita el daño a los tejidos y estructuras vitales adyacentes. Los primeros ensayos clínicos de fase I-II en humanos han demostrado la seguridad de la electroporación irreversible para terapia ablativa focal del cáncer de próstata y mostraron resultados alentadores considerando la preservación funcional. Los análisis histológicos después de la electroporación mostraron fibrosis sin ductos glandulares y tejido necrótico con clara demarcación entre el tejido glandular prostático no afecto y la zona de ablación. Los resultados oncológicos a corto plazo son prometedores; sin embargo son necesarios más datos y resultados oncológicos a largo plazo. Se están iniciando nuevos estudios con electroporación irreversible y otras modalidades de tratamiento focal para explorar las oportunidades de terapia focal en cáncer de próstata y para optimizar los protocolos de tratamiento actuales

Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study.

PURPOSE: Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. MATERIALS AND METHODS: Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. RESULTS: The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. CONCLUSIONS: Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

The correlation between the electrode configuration and histopathology of irreversible electroporation ablations in prostate cancer patients.

PURPOSE: Irreversible electroporation (IRE) is a novel minimally invasive therapy for prostate cancer using short electric pulses to ablate prostate tissue. The purpose of this study is to determine the IRE effects in prostate tissue and correlate electrode configuration with the histology of radical prostatectomy (RP) specimens. We hypothesize that the area within the electrode configuration is completely ablated and that the area within the electrode configuration is predictive for the ablated area after treatment. METHODS: A prospective phase I/II study was conducted in 16 consecutive patients with histopathologically confirmed prostate cancer scheduled for RP. Focal or extended IRE treatment of the prostate was performed 4 weeks prior to RP. The locations of the electrodes were used to calculate the planned ablation zone. Following RP, the specimens were processed into whole-mount sections, histopathology (PA) was assessed and ablation zones were delineated. The area of the tissue alteration was determined by measuring the surface. The planned and the histological ablation zones were compared, analysed per individual patient and per protocol (focal vs. extended). RESULTS: All cells within the electrode configuration were completely ablated and consisted only of necrotic and fibrotic tissue without leaving any viable cells. The histological ablation zone was always larger than the electrodes configuration (2.9 times larger for the 3 electrodes configuration and 2.5 times larger for the ≥4 electrode configuration). These ablation effects extended beyond the prostatic capsule in the neurovascular bundle in 13 out of 15 cases. CONCLUSIONS: IRE in prostate cancer results in completely ablated, sharply demarcated lesions with a histological ablation zone beyond the electrode configuration. No skip lesions were observed within the electrode configuration. CLINICAL TRIALS: ClinicalTrials.gov Identifier: NCT01790451 https://clinicaltrials.gov/ct2/show/NCT01790451.

Follow-up modalities in focal therapy for prostate cancer: results from a Delphi consensus project.

INTRODUCTION: Focal therapy can offer the middle ground for treatment between active surveillance and radical therapy in patients with low- and intermediate-risk prostate cancer. Factors that prohibit focal therapy from being standard of care are numerous. Several consensus projects have been conducted to position the utilization of imaging and trial design in focal therapy. However, the literature is still scarce on patient follow-up after focal therapy. For these reasons, an international multidisciplinary consensus project was established in order to reach consensus about a uniform follow-up protocol after focal therapy. OBJECTIVE: To standardize patient follow-up after focal therapy. MATERIALS AND METHODS: A literature study was performed, and a questionnaire was constructed. The questionnaire was sent out to 76 participants (70 % urologists, 28 % radiologists and 2 % biomedical engineers) in three consecutive rounds according to the Delphi method. In each round, the panelists were presented with the results of the previous round. Participants each had the opportunity to adapt, delete or add questions. The topics discussed pertaining to follow-up after focal therapy were as follows: (1) general,(2) biopsies, (3) PSA, (4) digital rectal examination (DRE), (5) imaging, (6) quality of life (QoL) and (7) registration and pooling of data. The project was concluded with a face-to-face meeting in which final conclusions were formulated. RESULTS: The follow-up after focal therapy should be a minimum of 5 years. The following modalities should be included in assessing post-treatment outcomes: multiparametric MRI (mpMRI), biopsies, assessment of erectile function, QoL, urinary symptoms and incontinence. A systematic 12-core TRUS biopsy combined with 4-6 targeted biopsy cores of the treated area and any suspicious lesion(s) should be performed after 1 year, and thereafter only when there is suspicion on imaging. The ideal way to perform targeted biopsies is to use TRUS-MRI fusion technology. PSA should be performed for research purposes, in the first year, every 3 months, and after the first year, every 6 months. mpMRI is the optimal imaging modality for follow-up after focal therapy. On a 1.5T scanner, an endorectal coil is strongly advised by the panel, whereas on a 3T machine, it is optional, however, it will improve image quality. The following sequences should be included: T2WI, DWI including high b values of >1,000 and ADC maps of DWI, DCE and T1WI. Imaging should be performed at 6 months and at 1 year following treatment; after the first year post-treatment, it should be performed every year until 5 years following treatment. All data should ideally be pooled in a common global database. CONCLUSION: Focal therapy is a relatively new form of treatment for prostate cancer. In order to include focal therapy as a standard of care treatment, consistent follow-up is necessary. By implementing the results of this consensus study, focal therapy users will be able to provide important and standardized outcome data.

The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol.

INTRODUCTION: Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. METHODS AND ANALYSIS: In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. ETHICS AND DISSEMINATION: The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. CONCLUSIONS: This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov database: NCT01790451.

Visual illusions and plate design: the effects of plate rim widths and rim coloring on perceived food portion size.

OBJECTIVE: The Delboeuf Illusion affects perceptions of the relative sizes of concentric shapes. This study was designed to extend research on the application of the Delboeuf illusion to food on a plate by testing whether a plate's rim width and coloring influence perceptual bias to affect perceived food portion size. DESIGN AND METHODS: Within-subjects experimental design. Experiment 1 tested the effect of rim width on perceived food portion size. Experiment 2 tested the effect of rim coloring on perceived food portion size. In both experiments, participants observed a series of photographic images of paired, side-by-side plates varying in designs and amounts of food. From each pair, participants were asked to select the plate that contained more food. Multilevel logistic regression examined the effects of rim width and coloring on perceived food portion size. RESULTS: Experiment 1: participants overestimated the diameter of food portions by 5% and the visual area of food portions by 10% on plates with wider rims compared with plates with very thin rims (P<0.0001). The effect of rim width was greater with larger food portion sizes. Experiment 2: participants overestimated the diameter of food portions by 1.5% and the visual area of food portions by 3% on plates with rim coloring compared with plates with no coloring (P=0.01). The effect of rim coloring was greater with smaller food portion sizes. CONCLUSION: The Delboeuf illusion applies to food on a plate. Participants overestimated food portion size on plates with wider and colored rims. These findings may help design plates to influence perceptions of food portion sizes.