Prospective close monitoring of the effect of vascular-targeted photodynamic therapy and high intensity focused ultrasound of localized prostate cancer by multiparametric magnetic resonance imaging.

PURPOSE: The aim of this study is to describe the anatomical and functional changes observed in multiparametric magnetic resonance imaging (mpMRI) during follow-up after focal therapy (FT) for localized prostate cancer (PCa). MATERIALS AND METHODS: In this prospective study, we analyzed pre- and postoperatively acquired mpMRI of 10 patients after FT (7 days; 3, 6, 9, 12 months). 7/10 (70%) patients underwent vascular-targeted photodynamic therapy (VTP). 3/10 (30%) patients underwent high-intensity focused ultrasound (HIFU). MpMR image analysis was performed using a semi-automatic software for segmentation of the prostate gland (PG) and tumor zones. Signal intensities (SI) of T2-weighted (T2w), T1-weighted (T1w),diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) images as well as volumes of the prostate gland (PGV) and tumor volumes (TV) were evaluated at each time point. RESULTS: The results showed a significant increase of PGV 7 days after FT (p = 0.042) and a significant reduction of PGV between 7 days and 6, 9 and 12 months after FT (p < 0.001). The TV increased significantly 7 days after FT (p < 0.001) and decreased significantly between 7 days and 12 months after FT (p < 0.001). There was a significant increase in SI of the ADC in the ablation zone after 6, 9 and 12 months after FT (p < 0.001). 1/9 patients (11%) had recurrent tumor on rebiopsy characterized as a a small focal lesion on mpMRI with strong diffusion restriction (low SI on ADC map and high SI on b-value DWI). CONCLUSION: MpMRI is able to represent morphologic changes of the ablated zone after FT and might be helpful to detect recurrent tumor.

Salvage High-Intensity Focused Ultrasound for Prostate Cancer after Radiation Failure: A Narrative Review.

For patients diagnosed with localized prostate cancer, there are multiple treatment options available. The traditional treatment modalities include radical prostatectomy and radiotherapy. Nevertheless, focal therapy, including high-intensity focused ultrasound (HIFU) and cryotherapy, has emerged as a less-invasive method in this setting. Some patients undergoing primary radiation therapy experience recurrence, but there is currently no consensus on the optimal approach for salvage treatment in such cases. The lack of robust data and randomized controlled trials comparing different whole-gland and focal salvage therapies presents a challenge in determining the ideal treatment strategy. This narrative review examines the prospective and retrospective data available on salvage HIFU following radiation therapy. Based on the literature, salvage HIFU for radio-recurrent prostate cancer has promising oncological outcomes, with an overall 5-year survival rate of around 85%, as well as incontinence rates of about 30% based on the patient's risk group, follow-up times, definitions used, and other aspects of the study. Salvage HIFU for prostate cancer proves to be an effective treatment modality for select patients with biochemical recurrence following radiotherapy.

Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer.

INTRODUCTION: Food and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients' perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. MATERIALS AND METHODS: Preferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. RESULTS: About 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. CONCLUSIONS: Results may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Combined holmium laser enucleation of the prostate with high-intensity focused ultrasound in treating patients with localized prostate cancer in a prostate with volume > 60 g: Oncological and functional outcomes from single-institution study.

OBJECTIVE: To assess the efficacy and safety of combined High-Intensity Focused Ultrasound (HIFU) and Holmium Laser Enucleation of the Prostate (HoLEP) in treating patients with both localized prostate cancer (PCa) and prostate > 60 g. METHODS: All patients who underwent HIFU for treatment of localized PCa were prospectively enrolled in our study. We reviewed records of patients undergoing procedures from January 2016 to January 2023. For patients with prostate sizes > 60 g, HoLEP was offered before HIFU to prevent worsened urinary symptoms post-treatment. Oncological outcomes-prostatic-specific (PSA) kinetics, recurrence rates, treatment failure - and functional results-Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS), and urinary complications were compared between patients undergoing combined HoLEP and HIFU with those underwent HIFU-monotherapy. RESULTS: Among 100 patients, 74 underwent HIFU-monotherapy and 26 underwent the combined HoLEP and HIFU. The majority had intermediate-risk PCa (67%). Pathologic assessment of HoLEP specimens showed no tumor evidence in 57% of cases. In comparison to the HIFU-only group, the combined group exhibited significantly lower PSA metrics across various intervals, however, no differences were found regarding overall and infield recurrences and treatment failure rates. While the combined treatment initially resulted in higher incontinence rates and shorter catheterization durations (P < 0.001), no significant difference in IPSS was observed during subsequent follow-ups. CONCLUSION: HoLEP and HIFU can be safely combined for the treatment of PCa in patients with >60 g prostate volume without compromising early oncological outcomes thereby expanding the therapeutic scope of HIFU in treating patients with localized PCa and large adenomas.

Oncological and Functional Outcomes of Whole-Gland HIFU as the Primary Treatment for Localized Prostate Cancer: A Systematic Review.

INTRODUCTION: High-intensity focused ultrasound (HIFU) is regarded as a promising alternative treatment option for localized prostate cancer (PCa) as it has been proposed to offer similar oncologic control to the standard of care, but with significantly reduced treatment-related side effects. This systematic literature review assesses the available evidence of whole-gland HIFU as primary treatment for localized PCa. METHODS: MEDLINE (PubMed) was searched for studies investigating oncological and functional outcomes following whole-gland HIFU as primary treatment for localized PCa. Our primary outcomes for the review were biochemical disease-free survival rates (BDFS), overall and PCa-specific survival rates as well as negative biopsy rates. Our secondary outcomes were functional results and complications of the treatment. RESULTS: A total of 375 articles were identified, of which 35 were included in the present review. All 35 articles were prospective or retrospective case series. Mean/median duration of follow-up across studies was 10.9 to 94 months, and 6618 patients were included in the review. The BDFS rate varied greatly across studies from 21.7% to 89.2% during follow-up. The 10-year PCa-specific survival rate following HIFU was 90%, 99%, and 100% in 3 studies. Negative biopsy rates post-HIFU ranged from 20% to 92.7% across studies. Common side effects to HIFU included urinary incontinence (grade 1: 0%-22.7%), erectile dysfunction (11.6%-77.1%), urinary tract infections (1.5%-47.9%), and bladder outlet obstruction mainly as urethral strictures (7%-41.2%). CONCLUSION: Great variation in oncological and functional outcomes was seen across studies. More prospective trials are needed before whole-gland HIFU can be considered as a treatment option for localized PCa.

High-Intensity Focused Ultrasound (Sonablate®) for Prostate Cancer: Preliminary Outcomes in Taiwan.

PURPOSE: We reported preliminary outcomes of high-intensity focused ultrasound (HIFU) [Sonablate®] in the combination of transurethral resection of the prostate for localized prostate cancer in Taiwan. METHODS: Seventy-seven patients using Sonablate® HIFU for localized prostate cancer were enrolled in this study from April 2021 to December 2022. Prostate-specific antigen biochemical recurrence, International Index of Erectile Function (IIEF)-5 scores, International Prostate Symptom Score (IPSS), quality of life (QoL) scores, and postoperative complications were recorded during follow-up. RESULTS: Overall, 19.5% of patients were low-risk, 36.4% were intermediate-risk, and 44.1% were high-risk according to the D'Amico risk classification. The median follow-up was 12.09 ± 5.85 months, and the biochemical-free survival rates for the low-, intermediate-, and high-risk groups were 100% (15/15), 96.4% (27/28), and 79.4% (27/34), respectively. Four patients (5.2%) received salvage radiotherapy and all maintained biochemical-free survival. The mean IPSS and QoL scores before versus after HIFU were 10.4 versus 6.8 (p = 0.003) and 3.2 versus 3.0 (p = 0.096), respectively. There was no statistically significant change in preoperative and postoperative IIEF scores (20.6 vs. 19; p = 0.062) in patients who had an IIEF score of >15 at baseline and received nerve-sparing procedures (subtotal ablation). CONCLUSIONS: The results of Sonablate® HIFU in Taiwan indicated adequate short-term cancer control, excellent potency, and continence preservation. HIFU can achieve improvement of IPSS with low complication rates.

[Oncological and functional results of focal treatment of localized prostate cancer with HIFU]. / Résultats oncologiques et fonctionnels du traitement focal du cancer de prostate localisé par HIFU.

INTRODUCTION: In recent years, improved diagnosis of prostate cancer has allowed the development of focal therapy, in order to reduce the morbidity of treatments. Our study assesses the medium-term oncological and functional results of FocalOne® HIFU treatment in localized prostate cancer. METHODS: This is a retrospective, multicentre study including patients with low- or intermediate-risk localized prostate cancer treated with Focal one HIFU between November 2014 and December 2019. The primary endpoint was the retreatment rate and subgroup analyses were performed to identify predictive factors of retreatment. RESULTS: One hundred and thirty-seven patients were included with a median follow-up of 25.5 months. Seventy percent of patients had clinical stage T2, 64% had an ISUP score of 2 or 3 on initial biopsies and 38% were treated with hemi-ablation. Follow-up biopsies were performed in 76.6% of patients during follow-up with 21.8% having clinically significant cancers. The retreatment rate at 24 months was 37.2%, with positive biopsies being the primary criterion for retreatment. Patients with a PSA>8ng/mL had a significantly higher retreatment rate. Finally, morbidity remained acceptable with 5.8% of patients requiring reoperation for complications and 21% for de novo erectile dysfunction. CONCLUSION: Our results are in agreement with those of the literature, seeming to indicate a lower morbidity of the focal treatment by HIFU compared to the radical treatments while offering an acceptable oncological control. Prospective randomized trials are ongoing.

External validation of biochemical recurrence definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound.

PURPOSE: This is an external validation of several biochemical recurrence definitions based on prostate specific antigen criteria (PSA). The purpose is to predict the need of additional treatment and failure after focal therapy using high intensity focused ultrasound (HIFU) for localized prostate cancer (PCa). MATERIALS AND METHODS: A total of 343 consecutive patients who underwent HIFU with Ablatherm® and Focal One® devices between June 2001 and November 2020 were identified. Treatment failure was defined as clinically significant PCa on postoperative biopsy, the need for salvage radical or systematic treatment, metastasis, or PCa-related death. The biochemical recurrence definitions tested were PSA nadir, time to PSA nadir, percentage of PSA reduction, Huber et al. criteria defined as PSA nadir + 1 ng/mL at 12 months or PSA nadir + 1.5 ng/mL at 24-36 months. Multivariable Cox regression analysis and decision-curve analysis were used to validate and compare criteria. Kaplan-Meier analysis was used to assess criteria associated with the highest accuracy. RESULTS: One hundred seventy-eight patients met the inclusion criteria and were analyzed. Overall, 61 (34%) and 41 (23%) patients had an additional treatment and failure with a median follow-up of 52 months. At multivariable analysis, model including Huber et al. criteria exhibited the highest Harrell's C-index for the prediction of the need of additional treatment (hazard ratio [HR]: 10, p < 0.001, c-index: 84%) and treatment failure (HR: 9.1, p < 0.001, c-index: 82%) as well as higher net benefit. The 60-months need of additional treatment and treatment failure-free survival were 89% and 98% compared to 26% and 49%, respectively, when stratified according to Huber et al. criteria (Log-rank test, p < 0.001). Similar results were found after excluding patient with non-clinically significant PCa at initial biopsy. CONCLUSIONS: We report an external validation of biochemical recurrence definitions predicting the need of additional treatment and failure after focal therapy using HIFU for localized PCa. Huber et al. criteria were identified as the most accurate and could be used to guide clinicians toward further evaluation and salvage treatments.

Diagnóstico ecográfico de la neoplasia prostática y su relación histológica / Ultrasound diagnosis of prostatic neoplasia and histological relationship

Introducción: El desarrollo de la tecnología con el ultrasonido transrectal ha permitido obtener imágenes diagnósticas de la glándula prostática; su interés deriva de la inmensa frecuencia de problemas clínicos, tanto benignos como malignos. El medio diagnóstico del cáncer de próstata se basa en una biopsia dirigida por ultrasonido transrectal en la mayoría de los casos. Objetivo: Determinar los hallazgos ultrasonográficos y su relación con estudios histopatológico en el diagnóstico de la neoplasia prostática, de los pacientes con sospecha, atendidos en la consulta de urooncología. Métodos: Se realizó un estudio descriptivo transversal en pacientes con sospecha clínica de cáncer prostático, procedentes del servicio de urología en el Hospital Celia Sánchez Manduley en el período comprendido entre julio de 2019 a julio de 2021; que acudieron a consulta con indicación de ultrasonido transrectal. El universo estuvo constituido por 105 pacientes. Se utilizaron criterios de inclusión y exclusión para la selección del universo, previo consentimiento informado de los pacientes. Las variables estudiadas fueron: edad, color de la piel, síntomas clínicos, hallazgos del ultrasonido transrectal, relación ecosonográfica- anatomopatológico. Resultados: Predominó el grupo de edad de 60 a 79 años, de la raza negra, con síntomas urinarios obstructivos bajos, con presencia del nódulo hipoecoico. Predominó la localización ultrasonográfica periférica, así como el adenocarcinoma prostático como hallazgos anatomopatológico encontrado a través de la biopsia. Conclusiones: Se demostró correlación ecográfica-histológica y anatomopatológica(AU)

Introduction: The development of transrectal ultrasound technology has made it possible to obtain diagnostic images of the prostate gland; its interest derives from the massive frequency of clinical problems, both benign and malignant. The diagnosis of prostate cancer is based on a transrectal ultrasound-guided biopsy in most cases. Objective: To determine the ultrasonographic findings and the how they relate with histopathological studies in the diagnosis of prostatic neoplasia in suspected patients treated in the uro-oncology clinic. Methods: A cross-sectional descriptive study was carried out in patients with clinical suspicion of prostate cancer, in the urology service at Celia Sánchez Manduley Hospital from July 2019 to July 2021; they attended the consultation with an indication for transrectal ultrasound. The universe consisted of 105 patients. Inclusion and exclusion criteria were used for the selection of the universe, with the prior informed consent of the patients. The variables studied were age, skin color, clinical symptoms, transrectal ultrasound findings, echosonographic-pathological relationship. Results: Predominance was observed of subjects from the age group of 60 to 79 years, black race, with lower obstructive urinary symptoms, and presence of hypoechoic nodule. Peripheral ultrasonographic location prevailed, as well as prostatic adenocarcinoma as pathological findings found through biopsy. Conclusions: Ultrasound-histological and pathological correlation was demonstrated(AU)

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience.

BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

High-intensity Focused Ultrasound for the Treatment of Prostate Cancer: A National Cohort Study Focusing on the Development of Stricture and Fistulae.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a novel therapy for prostate cancer. Owing to a lack of long-term data, HIFU is recommended for use only in the context of research. OBJECTIVE: To examine the trend for HIFU use nationally and rates of strictures and fistulae. DESIGN, SETTING, AND PARTICIPANTS: Patients undergoing HIFU for prostate cancer between April 2007 and March 2018 were studied in an English national database (Hospital Episode Statistics). Data on complications were included for patients with a minimum of 1-yr follow-up. Analysis of complications was controlled for other interventions. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Descriptive analyses of HIFU rates and the incidence of strictures and fistulae were carried out. Cox and logistic regression models were built for urethral stricture incidence. RESULTS AND LIMITATIONS: A total of 2320 HIFU treatments among 1990 patients were identified. The median age was 67yr (interquartile range 61-72). Some 1742 patients met the criteria for follow-up analysis. The highest-volume centre performed 1513 HIFU procedures, followed by 194 at the second highest. The number of HIFU procedures increased annually, rising from 196 to 283 per year. There were 208 patients (11.9%) who went on to have radiotherapy and 102 (5.9%) radical prostatectomy after HIFU. Following HIFU, stricture developed in 133/1290 patients (10.3%) and urinary fistula in 16/1240 (1.3%) before any further intervention. More recent years for HIFU were associated with a lower likelihood of stricture formation (2016/2017 vs 2007/2008: hazard ratio 0.30, 95% confidence interval 0.11-0.79; p=0.015). Limitations include the lack of staging information and unknown rates of HIFU outside of publicly funded health care. CONCLUSIONS: HIFU is performed at a large number of low-volume centres and complication rates do not differ from those for established therapies. PATIENT SUMMARY: This report highlights the trend for provision of high-intensity focused ultrasound treatment for prostate cancer in England. The results suggest that the rate of urethral structural complications may not be lower than that for established prostate cancer treatments.

Epidemiology and O-Serotypes of Extraintestinal Pathogenic Escherichia coli Disease in Patients Undergoing Transrectal Ultrasound Prostate Biopsy: A Prospective Multicenter Study.

PURPOSE: Extraintestinal pathogenic Escherichia coli (ExPEC) are a leading cause of invasive infections in adults. The study aimed to evaluate the incidence of microbiologically confirmed invasive ExPEC disease in patients undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), O-serotype distribution and antibiotic resistance profiles of associated E. coli isolates. MATERIALS AND METHODS: Adult men (≥18 years) undergoing TRUS-PNB were enrolled. The TRUS-PNB procedure was performed according to local standard of care, including preferences of prophylactic antibiotics. Clinical and microbiological data were collected. RESULTS: Of the 4,951 patients (mean age 66.9 years) enrolled 4,935 (99.7%) underwent TRUS-PNB (95.1% received prophylactic antibiotics); 98.9% completed the study. Overall incidence of invasive ExPEC disease was 0.67% (33/4,935 patients; 95% CI 0.46-0.94); highest incidence was in the U.S. (0.97%, 14/1,446; 95% CI 0.53-1.62). Prevalence of the 10 selected O-serotypes O1, O2, O4, O6, O8, O15, O16, O18, O25 and O75 was 52.0% (95% CI 31.3-72.2). E. coli isolates showed highest resistance rates to levofloxacin and ciprofloxacin (76%; 95% CI 54.8-90.6 for both). Among fluoroquinolone-resistant ExPEC isolates, prevalence of the 10 selected O-serotypes was 60%. CONCLUSIONS: This study provides an estimate of microbiologically confirmed invasive ExPEC disease incidence following TRUS-PNB. Information on E. coli O-serotype distribution and associated antibiotic resistance profiles from invasive ExPEC disease cases in the first 30 days following TRUS-PNB may help guiding antibiotic use and inform development of a prophylactic ExPEC vaccine.

A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice.

High-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV-2) vaccine. First, we observed that in HSV-2-positive cervical intraepithelial neoplasia (CIN) II patients, HIFU treatment induced significantly higher anti-HSV-2 neutralization response than surgical removal. Next, we tested the efficacy of HIFU-treated, UV-inactivated HSV-2-infected cells as a proof-of-concept vaccine in mice. Our data showed that HIFU-treated formulation significantly enhanced HSV-2 antibody titers and neutralization titers, compared to UV-, microwave (MW)-, or freeze-thaw (FT)-treated formulations. HIFU treatment also promoted the Th1/2 cell-mediated response. A long-term full protection was observed in mice that received the HIFU-treated formulation, and no weight loss was detected. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.IMPORTANCE High-intensity focused ultrasound (HIFU) is mainly used in tumor ablation and tumor vaccinology study. It has been shown to induce immune sensitization and enhance tumor responsiveness to other therapies. Our study has shown enhanced anti-HSV-2 response in HIFU-treated CIN II patients. Furthermore, in a murine model, we have demonstrated that HIFU-treated HSV-2 vaccine induced long-term protective immunity against lethal challenge. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.

Hybrid TRUS/CT with optical tracking for target delineation in image-guided adaptive brachytherapy for cervical cancer.

OBJECTIVE: To prospectively compare the interobserver variability of combined transrectal ultrasound (TRUS)/computed tomography (CT)- vs. CT only- vs. magnetic resonance imaging (MRI) only-based contouring of the high-risk clinical target volume (CTVHR) in image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). METHODS: Five patients with LACC (FIGO stages IIb-IVa) treated with radiochemotherapy and IGABT were included. CT, TRUS, and T2-weighted MRI images were performed after brachytherapy applicator insertion. 3D-TRUS image acquisition was performed with a customized ultrasound stepper device and software. Automatic applicator reconstruction using optical tracking was performed in the TRUS dataset and TRUS and CT images were fused with rigid image registration with the applicator as reference structure. The CTVHR (based on the GEC-ESTRO recommendations) was contoured by five investigators on the three modalities (CTVHR_CT, CTVHR_TRUS-CT, and CTVHR_MRI). A consensus reference CTVHR_MRI (MRIref) was defined for each patient. Descriptive statistics and overlap measures were calculated using RTslicer (SlicerRT Community and Percutaneous Surgery Laboratory, Queen's University, Canada), comparing contours of every observer with one another and with the MRIref. RESULTS: The interobserver coefficient of variation was 0.18 ± 0.05 for CT, 0.10 ± 0.04 for TRUS-CT, and 0.07 ± 0.03 for MRI. Interobserver concordance in relation to the MRIref expressed by the generalized conformity index was 0.75 ± 0.04 for MRI, 0.51 ± 0.10 for TRUS-CT, and 0.48 ± 0.06 for CT. The mean CTVHR_CT volume of all observers was 71% larger than the MRIref volume, whereas the mean CTVHR_TRUS-CT volume was 15% larger. CONCLUSION: Hybrid TRUS-CT as an imaging modality for contouring the CTVHR in IGABT for LACC is feasible and reproducible among multiple observers. TRUS-CT substantially reduces overestimation of the CTVHR volume of CT alone while maintaining similar interobserver variability.

MRI-Targeted Prostate Biopsy: What Radiologists Should Know.

Transrectal ultrasound (TRUS)-guided systematic biopsy, the current gold standard for the detection of prostate cancer, suffers from low sensitivity for clinically significant cancer. The use of diagnostic multiparametric MRI has increased the relevance of targeted biopsy techniques such as MRI-TRUS fusion biopsy and direct (in-bore) MRI-guided biopsy, which have higher detection rate for clinically significant cancer. Although primarily used in patients who remain at high clinical suspicion for prostate cancer despite a negative systematic biopsy, with the increasing use of upfront diagnostic MRI, these biopsies are expected to replace routine systematic biopsies. This pictorial essay aims to enhance our understanding of the concepts of these biopsy techniques so that they can be performed safely and provide maximum diagnostic yield.

Prediction of prostate cancer Gleason score upgrading from biopsy to radical prostatectomy using pre-biopsy multiparametric MRI PIRADS scoring system.

An increase or 'upgrade' in Gleason Score (GS) in prostate cancer following Transrectal Ultrasound (TRUS) guided biopsies remains a significant challenge to overcome. to evaluate whether MRI has the potential to narrow the discrepancy of histopathological grades between biopsy and radical prostatectomy, three hundred and thirty men treated consecutively by laparoscopic radical prostatectomy (LRP) between July 2014 and January 2019 with localized prostate cancer were included in this study. Independent radiologists and pathologists assessed the MRI and histopathology of the biopsies and prostatectomy specimens respectively. A multivariate model was constructed using logistic regression analysis to assess the ability of MRI to predict upgrading in biopsy GS in a nomogram. A decision-analysis curve was constructed assessing impact of nomogram using different thresholds for probabilities of upgrading. PIRADS scores were obtained from MRI scans in all the included cases. In a multivariate analysis, the PIRADS v2.0 score significantly improved prediction ability of MRI scans for upgrading of biopsy GS (p = 0.001, 95% CI [0.06-0.034]), which improved the C-index of predictive nomogram significantly (0.90 vs. 0.64, p < 0.05). PIRADS v2.0 score was an independent predictor of postoperative GS upgrading and this should be taken into consideration while offering treatment options to men with localized prostate cancer.

A pilot study of the shapes of ablation lesions in the canine prostate by laser, radiofrequency and microwave and their clinical significance.

To explore the shape characteristics of ablation lesions created via laser ablation (LA), radiofrequency ablation (RFA) and microwave ablation (MWA) in canine prostates and the clinical significance of these characteristics, six adult male beagles were randomly assigned to the LA, RFA, and MWA groups. These ablations were performed with common parameters applied in clinical practice (LA, 3 W/1200 J; RFA and MWA, 30 W/120 s). One ablation lesion was created in each lobe of the prostate via the ablation technique, resulting in a total of twelve ablation lesions. Transrectal ultrasound (TRUS) was used as guidance during puncture and to monitor changes in the ablation lesions. Finally, the ablation efficacy was assessed using transrectal contrast-enhanced ultrasonography (CEUS), and the transverse diameter (TRD), anteroposterior diameter (APD) and longitudinal diameter (LD) of each ablation lesion were measured. The volume (V) and the ratio (R) value were calculated. R reflects the shape characteristic of the ablation lesion (the R value close to 1.0 indicates a more spherical shape). The R values of the ablation lesions were 0.89 ± 0.02, 0.72 ± 0.01, and 0.65 ± 0.03 for RFA, MWA and LA, respectively, and they were significantly different (P = 0.027). The volumes of the ablation lesions were 2.17 ± 0.10 ml, 1.51 ± 0.20 ml, and 0.79 ± 0.07 ml for MWA, LA and RFA, respectively, and they were also significantly different (P = 0.001). The three abovementioned thermal ablation techniques with common parameters in clinical practice can be used for ablation in the prostate. The shapes and volumes of the ablation lesions of the three techniques were varied: The RFA-created lesions had the lowest volumes and were more spherical in shape, demonstrating that RFA could be used for the treatment of relatively small lesions or tumours adjacent to vital organs. The MWA lesions had the largest size with a spherical shape, which could be advantageous for the ablation of tumours with relatively large sizes. The sizes of the ablation lesions created via LA were between those of RFA and MWA but presented more oval in shape, suggesting that this method is highly appropriate for the ablation of benign prostatic hyperplasia (BPH).

Implications of faecal ESBL carriers undergoing TRUS-guided prostate biopsy (TRUSPB): role of screening prior to TRUSPB.

INTRODUCTION: Modification of antibiotic prophylaxis prior to transrectal ultrasound-guided prostate biopsy (TRUSPB) based on pre-procedure rectal culture results is effective for prevention of infection from fluoroquinolone (FQ)-resistant and extended-spectrum beta-lactamase (ESBL) Escherichia coli strains. This has several implications for service delivery and cost. Our aim was to audit sepsis rates after introduction of ESBL screening and to identify risk factors for FQ resistance in ESBL strains and factors for sepsis risk. METHODS: This was a prospective cohort study from 2013 to 2016. TRUSPB patients underwent pre-procedure rectal swabs. ESBL-positive patients received amikacin in addition to ciprofloxacin prophylaxis. Patients filled a formal risk assessment questionnaire prior to biopsy. RESULTS: Sepsis rate after introduction of targeted prophylaxis reduced from 3.1% (2009-2012) to 1.4% (2013-2016). Of 38 ESBL patients, n = 5 (13%) developed severe post-TRUSPB sepsis. Among the FQ-resistant ESBL producers, the sepsis rate was 24%. Predictive factor for FQ resistance in ESBL producers included-antibiotic use in the last 3 months (OR 15). The logistic regression analysis did not identify any significant factor for post-TRUSPB sepsis in ESBL-positive patients once they had received additional prophylaxis. CONCLUSION: In the face of rising TRUSPB sepsis and higher sepsis rates with ESBL carriers despite additional prophylaxis, introduction of a targeted antibiotic prophylaxis prior to TRUSPB sepsis prostate biopsies based on rectal swabs or urine cultures may reduce sepsis rates or clinicians may find themselves leaning towards increasingly performing transperineal biopsies with lower sepsis rates supporting the 'trexit' initiative.