Device-Assisted Therapy in Non-Muscle-Invasive Bladder Cancer.

Intravesical therapy is a critical component in the management of non-muscle-invasive bladder cancer (NMIBC), as it reduces rates of disease recurrence and progression. However, the presence of physiologic barriers in the urothelium reduces the penetration and distribution of intravesical chemotherapy, thereby limiting the therapeutic potential. Much progress to overcome this challenge has been made in the realm of intravesical device-assisted therapy. Novel device-assisted treatments include hyperthermia, the radiofrequency-induced thermochemotherapy effect, electromotive drug administration, and implantable drug delivery systems. Notably, chemotherapy enhanced by these device-assisted systems has shown improved oncologic efficacy relative to standard intravesical chemotherapy and comparable outcomes relative to Bacillus Calmette-Guérin (BCG) therapy in patients with intermediate- or high-risk NMIBC. Recent studies also support the utility of device-assisted therapy as a salvage treatment option in patients with BCG-unresponsive disease. Ongoing randomized controlled trials and prospective investigations will further help clarify indications and long-term safety outcomes of these treatment modalities in NMIBC. Herein, we present a comprehensive review of device-assisted therapies and discuss their clinical utilities for the management of NMIBC in the modern era.

Comparison of Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) and Prostate Imaging after Focal Ablation (PI-FAB) for Detecting Recurrent Prostate Cancer at Prostate MRI.

RATIONALE AND OBJECTIVES: The increasing use of focal therapy (FT) in localized prostate cancer (PCa) management requires a standardized MRI interpretation system to detect recurrent clinically significant PCa (csPCa). This pilot study evaluates the novel Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) and compares its performance to that of the Prostate Imaging after Focal Ablation (PI-FAB) system. MATERIALS AND METHODS: This retrospective study included 38 patients who underwent primary FT for localized PCa, with follow-up multiparametric MRI (mpMRI) and biopsy. Two radiologists assessed the mpMRIs using both PI-FAB and TARGET independently. Diagnostic performance metrics and area under the receiver operating characteristic curve (AUC) were calculated. Inter-reader and intrareader agreement were assessed using Cohen's κ and Kendall's τ. RESULTS: 14 patients had recurrent csPCa. PI-FAB showed high sensitivity (92.9% for both readers) and NPV (reader 1: 93.8%, reader 2: 92.9%) but moderate specificity (reader 1: 62.5%, reader 2: 54.2%). TARGET demonstrated lower sensitivity for one reader (reader 1: 78.6%, reader 2: 92.9%) but higher specificity (reader 1: 79.2%, reader 2: 62.5%) for both readers. Both systems displayed moderate inter-reader agreement (κ = 0.56 for PI-FAB, 0.57 for TARGET). CONCLUSION: PI-FAB and TARGET exhibit similar performances in post-FT MRI. While PI-FAB had consistently high sensitivity, TARGET offered higher specificity for one reader. Moderate agreement levels demonstrate the viability of these systems in clinical settings and a promise for improvement.

Castration Levels of Testosterone Results in Atrophy of Androgen-Sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism.

OBJECTIVES: To evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship. METHODS: Data was prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width. RESULTS: Thirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dl, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (p<0.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (p=0.032). CONCLUSIONS: Androgen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.

External Validation of a Previously Developed Deep Learning-based Prostate Lesion Detection Algorithm on Paired External and In-House Biparametric MRI Scans.

Purpose To evaluate the performance of an artificial intelligence (AI) model in detecting overall and clinically significant prostate cancer (csPCa)-positive lesions on paired external and in-house biparametric MRI (bpMRI) scans and assess performance differences between each dataset. Materials and Methods This single-center retrospective study included patients who underwent prostate MRI at an external institution and were rescanned at the authors' institution between May 2015 and May 2022. A genitourinary radiologist performed prospective readouts on in-house MRI scans following the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 or 2.1 and retrospective image quality assessments for all scans. A subgroup of patients underwent an MRI/US fusion-guided biopsy. A bpMRI-based lesion detection AI model previously developed using a completely separate dataset was tested on both MRI datasets. Detection rates were compared between external and in-house datasets with use of the paired comparison permutation tests. Factors associated with AI detection performance were assessed using multivariable generalized mixed-effects models, incorporating features selected through forward stepwise regression based on the Akaike information criterion. Results The study included 201 male patients (median age, 66 years [IQR, 62-70 years]; prostate-specific antigen density, 0.14 ng/mL2 [IQR, 0.10-0.22 ng/mL2]) with a median interval between external and in-house MRI scans of 182 days (IQR, 97-383 days). For intraprostatic lesions, AI detected 39.7% (149 of 375) on external and 56.0% (210 of 375) on in-house MRI scans (P < .001). For csPCa-positive lesions, AI detected 61% (54 of 89) on external and 79% (70 of 89) on in-house MRI scans (P < .001). On external MRI scans, better overall lesion detection was associated with a higher PI-RADS score (odds ratio [OR] = 1.57; P = .005), larger lesion diameter (OR = 3.96; P < .001), better diffusion-weighted MRI quality (OR = 1.53; P = .02), and fewer lesions at MRI (OR = 0.78; P = .045). Better csPCa detection was associated with a shorter MRI interval between external and in-house scans (OR = 0.58; P = .03) and larger lesion size (OR = 10.19; P < .001). Conclusion The AI model exhibited modest performance in identifying both overall and csPCa-positive lesions on external bpMRI scans. Keywords: MR Imaging, Urinary, Prostate Supplemental material is available for this article. © RSNA, 2024.

A novel pathogenic germline chromosome 3 inversion in von Hippel-Lindau disease.

von Hippel-Lindau (VHL) is an autosomal-dominant hereditary tumour susceptibility disease associated with pathogenic germline variants in the VHL tumour suppressor gene. VHL patients are at increased risk of developing multiple benign and malignant tumours. Current CLIA-based genetic tests demonstrate a very high detection rate of germline VHL variants in patients with clinical manifestations of VHL. In this report, we describe a large family with canonical VHL manifestations, for which no germline alteration had been detected by conventional germline testing. We identified a novel 291 kb chromosomal inversion involving chromosome 3p in affected family members. This inversion disrupts the VHL gene between exon 2 and exon 3 and is thereby responsible for the disease observed in this family.

Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis.

Background: Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a subset of cancers and have been shown to confer sensitivity to immune checkpoint inhibition (ICI); however, there is a lack of prospective data in urothelial carcinoma (UC). Methods and analysis: We performed a systematic review to estimate the prevalence of dMMR and MSI-H in UC, including survival and clinical outcomes. We searched for studies published up to 26 October 2022 in major scientific databases. We screened 1745 studies and included 110. Meta-analyses were performed if the extracted data were suitable. Results: The pooled weighted prevalences of dMMR in bladder cancer (BC) and upper tract UC (UTUC) were 2.30% (95% CI 1.12% to 4.65%) and 8.95% (95% CI 6.81% to 11.67%), respectively. The pooled weighted prevalences of MSI-H in BC and UTUC were 2.11% (95% CI 0.82% to 5.31%) and 8.36% (95% CI 5.50% to 12.53%), respectively. Comparing localised versus metastatic disease, the pooled weighted prevalences for MSI-H in BC were 5.26% (95% CI 0.86% to 26.12%) and 0.86% (95% CI 0.59% to 1.25%), respectively; and in UTUC, they were 18.04% (95% CI 13.36% to 23.91%) and 4.96% (95% CI 2.72% to 8.86%), respectively. Cumulatively, the response rate in dMMR/MSI-H metastatic UC treated with an ICI was 22/34 (64.7%) compared with 1/9 (11.1%) with chemotherapy. Conclusion: Both dMMR and MSI-H occur more frequently in UTUC than in BC. In UC, MSI-H occurs more frequently in localised disease than in metastatic disease. These biomarkers may predict sensitivity to ICI in metastatic UC and resistance to cisplatin-based chemotherapy.

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

PURPOSE: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts. METHODS: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208). RESULTS: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.

Deep learning-based image quality assessment: impact on detection accuracy of prostate cancer extraprostatic extension on MRI.

OBJECTIVE: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm. MATERIALS AND METHODS: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE. RESULTS: A total of 773 consecutive patients (median age 61 [IQR 56-67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67-76%] vs. 63% [95% CI 56-69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62-80%] vs. 75% [95% CI 63-85%]), positive predictive value (44% [95% CI 39-49%] vs. 38% [95% CI 32-43%]), or negative predictive value (89% [95% CI 86-92%] vs. 89% [95% CI 85-93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54-5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63-4.24; P = 0.24). CONCLUSION: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology.

Cumulative Impact of Serial Partial Nephrectomy for the Treatment of Recurrent Renal Masses.

PURPOSE: Reoperative partial nephrectomy (RePN) offers several advantages for the treatment of recurrent, multifocal renal masses. RePN has been previously demonstrated to be technically feasible and delay the need for renal replacement therapy. However, there is still inherent complexity and known risks to reoperative nephrectomy. We studied the largest population of RePNs to characterize renal functional outcomes and the likelihood of intra- and postoperative complications. MATERIALS AND METHODS: Query of an institutional surgical registry was conducted. Demographic data, serum creatinine for estimated glomerular filtration rate (eGFR), and protein dipstick results were assessed within 1 week prior to surgery, and postoperative function assessments were studied within a year of surgery. RePN was defined as serial surgical resection of the ipsilateral renal unit. RESULTS: A total of 1131 partial nephrectomies performed on 663 patients at a single center were retrospectively evaluated. In reoperative cases, median number of operations per renal unit was 2 (range: 2-6). There was a stepwise decline in eGFR with an average decline of 6.1 with each RePN. With each subsequent nephrectomy, surgical duration, estimated blood loss, and incidence of preoperative anemia increased. Postoperative eGFR showed a significant positive association with preoperative eGFR, while negative associations were found with age, number of previous ipsilateral partial nephrectomies, number of tumors, and largest tumor size. High-grade complications were associated with the number of ipsilateral partial nephrectomies, tumor count, and tumor size. Robotic or laparoscopic procedures exhibited a likelihood of grade 3 or greater complications compared to open surgery. CONCLUSIONS: RePN contributes to renal dysfunction and an increased risk of surgical complications. Intraoperative blood loss and surgical duration increase with subsequent nephrectomy. Such risks are dependent on the number of prior operative interventions on the kidney, suggesting a stepwise progression of surgical morbidity.

Evaluation of a Cascaded Deep Learning-based Algorithm for Prostate Lesion Detection at Biparametric MRI.

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results. Materials and Methods This secondary analysis of a prospective registry included consecutive patients with suspected or known PCa who underwent mpMRI, US-guided systematic biopsy, or combined systematic and MRI/US fusion-guided biopsy between April 2019 and September 2022. All lesions were prospectively evaluated using Prostate Imaging Reporting and Data System version 2.1. The lesion- and participant-level performance of a previously developed cascaded deep learning algorithm was compared with histopathologic outcomes and radiologist readings using sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC). Results A total of 658 male participants (median age, 67 years [IQR, 61-71 years]) with 1029 MRI-visible lesions were included. At histopathologic analysis, 45% (294 of 658) of participants had lesions of International Society of Urological Pathology (ISUP) grade group (GG) 2 or higher. The algorithm identified 96% (282 of 294; 95% CI: 94%, 98%) of all participants with clinically significant PCa, whereas the radiologist identified 98% (287 of 294; 95% CI: 96%, 99%; P = .23). The algorithm identified 84% (103 of 122), 96% (152 of 159), 96% (47 of 49), 95% (38 of 40), and 98% (45 of 46) of participants with ISUP GG 1, 2, 3, 4, and 5 lesions, respectively. In the lesion-level analysis using radiologist ground truth, the detection sensitivity was 55% (569 of 1029; 95% CI: 52%, 58%), and the PPV was 57% (535 of 934; 95% CI: 54%, 61%). The mean number of false-positive lesions per participant was 0.61 (range, 0-3). The lesion segmentation DSC was 0.29. Conclusion The AI algorithm detected cancer-suspicious lesions on biparametric MRI scans with a performance comparable to that of an experienced radiologist. Moreover, the algorithm reliably predicted clinically significant lesions at histopathologic examination. ClinicalTrials.gov Identifier: NCT03354416 © RSNA, 2024 Supplemental material is available for this article.

Outcomes of a universal germline screening program in a community urology practice.

The role of germline genetic testing in urologic oncology has expanded in recent years. However, implementation of genetic testing in community practices remains a challenge, often due to limited access to qualified genetics trained providers. In this study, we report outcomes of a universal germline screening program in a community urology practice. Between November 2021 and September 2022, all patients referred for urology clinic visits at Frederick Health (Frederick, MD, USA) were provided an online genetics screening questionnaire prior to the visit. Responses were compared against National Comprehensive Cancer Network (NCCN) criteria for germline testing. Those who met criteria were provided educational materials at the end of the questionnaire, and then counseled by a trained urologic oncologist (HC) in the clinic or referred to a genetic counselor prior to testing. Testing was performed with a 36-gene pan-cancer panel (CancerNext) or a 14-gene targeted prostate cancer panel (ProstateNext), with or without additional RNA analysis (RNAinsight) (Ambry Genetics, CA, USA). Demographic and clinical parameters, as well as genetic testing results, were retrospectively collected under IRB approval. In the study period, 765 patients were seen over 1370 clinic visits. Of these, 505 patients (66.0%) completed the screening questionnaire. The majority were completed via email (54.5%) with the remainder (45.5%) via text message. Of the patients who completed screening, 125/505 (24.7%) met NCCN criteria for germline testing. 58/125 patients (46.4%) who met criteria underwent germline testing, of whom 5/58 (8.6%) had distinct pathogenic mutations identified. These included actionable mutations in BRCA1, BRCA2, and CHEK2, as well as an additional pathogenic mutation in NBN. Variants of unknown significance were identified in 8/58 patients (13.8%) in 11 total genes. Challenges to implementation of this program included meeting institutional requirements for genetic testing consent, facilitating specimen collection in clinic, and integration of results into the electronic health record. Genetic risk assessment for high-risk individuals is feasible as part of a universal screening program in a community urology practice. Approximately 8% of tested patients were found to have pathogenic germline mutations, which is consistent with contemporary tertiary referral cohorts.

Reducing False-Positives Due to Urinary Stagnation in the Prostatic Urethra on 18 F-DCFPyL PSMA PET/CT With MRI.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeting PET radiotracers reveal physiologic uptake in the urinary system, potentially misrepresenting activity in the prostatic urethra as an intraprostatic lesion. This study examined the correlation between midline 18 F-DCFPyL activity in the prostate and hyperintensity on T2-weighted (T2W) MRI as an indication of retained urine in the prostatic urethra. PATIENTS AND METHODS: Eighty-five patients who underwent both 18 F-DCFPyL PSMA PET/CT and prostate MRI between July 2017 and September 2023 were retrospectively analyzed for midline radiotracer activity and retained urine on postvoid T2W MRIs. Fisher's exact tests and unpaired t tests were used to compare residual urine presence and prostatic urethra measurements between patients with and without midline radiotracer activity. The influence of anatomical factors including prostate volume and urethral curvature on urinary stagnation was also explored. RESULTS: Midline activity on PSMA PET imaging was seen in 14 patients included in the case group, whereas the remaining 71 with no midline activity constituted the control group. A total of 71.4% (10/14) and 29.6% (21/71) of patients in the case and control groups had urethral hyperintensity on T2W MRI, respectively ( P < 0.01). Patients in the case group had significantly larger mean urethral dimensions, larger prostate volumes, and higher incidence of severe urethral curvature compared with the controls. CONCLUSIONS: Stagnated urine within the prostatic urethra is a potential confounding factor on PSMA PET scans. Integrating PET imaging with T2W MRI can mitigate false-positive calls, especially as PSMA PET/CT continues to gain traction in diagnosing localized prostate cancer.

Automated Detection and Grading of Extraprostatic Extension of Prostate Cancer at MRI via Cascaded Deep Learning and Random Forest Classification.

RATIONALE AND OBJECTIVES: Extraprostatic extension (EPE) is well established as a significant predictor of prostate cancer aggression and recurrence. Accurate EPE assessment prior to radical prostatectomy can impact surgical approach. We aimed to utilize a deep learning-based AI workflow for automated EPE grading from prostate T2W MRI, ADC map, and High B DWI. MATERIAL AND METHODS: An expert genitourinary radiologist conducted prospective clinical assessments of MRI scans for 634 patients and assigned risk for EPE using a grading technique. The training set and held-out independent test set consisted of 507 patients and 127 patients, respectively. Existing deep-learning AI models for prostate organ and lesion segmentation were leveraged to extract area and distance features for random forest classification models. Model performance was evaluated using balanced accuracy, ROC AUCs for each EPE grade, as well as sensitivity, specificity, and accuracy compared to EPE on histopathology. RESULTS: A balanced accuracy score of .390 ± 0.078 was achieved using a lesion detection probability threshold of 0.45 and distance features. Using the test set, ROC AUCs for AI-assigned EPE grades 0-3 were 0.70, 0.65, 0.68, and 0.55 respectively. When using EPE≥ 1 as the threshold for positive EPE, the model achieved a sensitivity of 0.67, specificity of 0.73, and accuracy of 0.72 compared to radiologist sensitivity of 0.81, specificity of 0.62, and accuracy of 0.66 using histopathology as the ground truth. CONCLUSION: Our AI workflow for assigning imaging-based EPE grades achieves an accuracy for predicting histologic EPE approaching that of physicians. This automated workflow has the potential to enhance physician decision-making for assessing the risk of EPE in patients undergoing treatment for prostate cancer due to its consistency and automation.

Timing, incidence and management of delayed bleeding after partial nephrectomy in patients at risk for recurrent, bilateral, multifocal renal tumors.

INTRODUCTION: Delayed bleeding is a potentially serious complication after partial nephrectomy (PN), with reported rates of 1%-2%. Patients with multiple renal tumors, including those with hereditary forms of kidney cancer, are often managed with resection of multiple tumors in a single kidney which may increase the risk of delayed bleeding, though outcomes have not previously been reported specifically in this population. The objective of this study was to evaluate the incidence and timing of delayed bleeding as well as the impact of intervention on renal functional outcomes in a cohort primarily made up of patients at risk for bilateral, multifocal renal tumors. METHODS: A retrospective review of a prospectively maintained database of patients with known or suspected predisposition to bilateral, multifocal renal tumors who underwent PN from 2003 to 2023 was conducted. Patients who presented with delayed bleeding were identified. Patients with delayed bleeding were compared to those without. Comparative statistics and univariate logistic regression were used to determine potential risk factors for delayed bleeding. RESULTS: A total of 1256 PN were performed during the study period. Angiographic evidence of pseudoaneurysm, AV fistula and/or extravasation occurred in 24 cases (1.9%). Of these, 21 were symptomatic presenting with gross hematuria in 13 (54.2%), decreasing hemoglobin in 4(16.7%), flank pain in 2(8.3%), and mental status change in 2 (8.3%), while 3 patients were asymptomatic. Median number of resected tumors was 5 (IQR 2-8). All patients underwent angiogram with super-selective embolization. Median time to bleed event was 13.5 days (IQR 7-22). Factors associated with delayed bleeding included open approach (OR 2.2, IQR(1.06-5.46), P = 0.04 and left-sided surgery (OR 4.93, IQR(1.67-14.5), P = 0.004. Selective embolization had little impact on ultimate renal functional outcomes, with a median change of 11% from the baseline eGFR after partial nephrectomy and embolization. One patient required total nephrectomy for refractory bleeding after embolization. CONCLUSIONS: Delayed bleeding after PN in a cohort of patients with multifocal tumors is an infrequent event, with similar rates to single tumor series. Patients should be counseled regarding timing and symptoms of delayed bleeding and multidisciplinary management with interventional radiology is critical for timely diagnosis and treatment.

Automated prostate gland segmentation in challenging clinical cases: comparison of three artificial intelligence methods.

OBJECTIVE: Automated methods for prostate segmentation on MRI are typically developed under ideal scanning and anatomical conditions. This study evaluates three different prostate segmentation AI algorithms in a challenging population of patients with prior treatments, variable anatomic characteristics, complex clinical history, or atypical MRI acquisition parameters. MATERIALS AND METHODS: A single institution retrospective database was queried for the following conditions at prostate MRI: prior prostate-specific oncologic treatment, transurethral resection of the prostate (TURP), abdominal perineal resection (APR), hip prosthesis (HP), diversity of prostate volumes (large ≥ 150 cc, small ≤ 25 cc), whole gland tumor burden, magnet strength, noted poor quality, and various scanners (outside/vendors). Final inclusion criteria required availability of axial T2-weighted (T2W) sequence and corresponding prostate organ segmentation from an expert radiologist. Three previously developed algorithms were evaluated: (1) deep learning (DL)-based model, (2) commercially available shape-based model, and (3) federated DL-based model. Dice Similarity Coefficient (DSC) was calculated compared to expert. DSC by model and scan factors were evaluated with Wilcox signed-rank test and linear mixed effects (LMER) model. RESULTS: 683 scans (651 patients) met inclusion criteria (mean prostate volume 60.1 cc [9.05-329 cc]). Overall DSC scores for models 1, 2, and 3 were 0.916 (0.707-0.971), 0.873 (0-0.997), and 0.894 (0.025-0.961), respectively, with DL-based models demonstrating significantly higher performance (p < 0.01). In sub-group analysis by factors, Model 1 outperformed Model 2 (all p < 0.05) and Model 3 (all p < 0.001). Performance of all models was negatively impacted by prostate volume and poor signal quality (p < 0.01). Shape-based factors influenced DL models (p < 0.001) while signal factors influenced all (p < 0.001). CONCLUSION: Factors affecting anatomical and signal conditions of the prostate gland can adversely impact both DL and non-deep learning-based segmentation models.

Neuropathic pain in burn patients - A common problem with little literature: A systematic review.

BACKGROUND: The prevalence of neuropathic pain (NP) in burn patients is reported in the literature to be as high as 80%1. Given the complexity of NP in burn patients and the wide range of treatments available, a systematic review of the literature is warranted to summarize our current understanding of management and treatment of NP in this population. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The following databases were queried to identify relevant articles: PubMed, Cochrane, Embase, Scopus, Ovid, and Web of Science. The main outcome measures were incidence and management of NP. Secondary outcomes included risk factors for NP. RESULTS: Included articles presented findings from 11 different countries, capturing outcomes for 4366 patients. Risk factors for neuropathic pain in burn patients were identified, including older age, alcohol and substance abuse, current daily smoking, greater % total body surface area burns (TBSA), and longer hospitalizations. Pharmacologic treatments included gabapentin/pregabalin (n = 7), ascorbic acid (n = 1), and lidocaine (n = 1). Overall, the studies showed varied results regarding the efficacy of pharmacological treatments. While certain studies demonstrated gabapentanoids to be effective in reducing neuropathic symptoms, others found conflicting results. With regards to non-pharmacologic treatments, electroconvulsive therapy (n = 1), electropuncture (n = 1), nerve release/reconstruction (n = 2), and somatosensory feedback rehabilitation (n = 1) were used and demonstrated promise in reducing pain intensity and improving functionality. CONCLUSIONS: Despite NP afflicting the majority of burn patients long after their injury, this systematic review demonstrates insufficient evidence on the pathophysiology, outcomes, and risk factors in NP, as well as the efficacy of various therapies. Future prospective and randomized studies evaluating the etiology of these factors can substantially improve our treatment strategies. This can allow for the development of well-delineated and evidence-based protocols in NP management in hopes of improving quality of life and both psychological and physical function in burn patients.

Critical Prognostic Factors in Cerebral Venous Sinus Thrombosis: An Observational Study.

Background: Cerebral venous sinus thrombosis (CVST) presents with a wide variety of neurological symptoms in various combinations and has a high mortality rate of up to 50%. Recent advances in neuroimaging and therapeutic interventions have brought it down to 10%-20%. The study aims to identify critical prognostic factors associated with poor outcomes in patients with CVST. Materials and Methods: All cases of CVST aged >18 years from July 2015 to July 2020 who were not terminally ill and bedridden before the illness were evaluated at the entry point for various risk factors and after 30 days for outcome assessment with the modified Rankin scale (mRS). The outcome was dichotomized, applying mRS <3 as a good outcome, and analyzed with the Chi-square test or the Fischer's exact test in a bivariate analysis to identify associated variables. Results: A total of 149 subjects were studied. Glasgow Comma Scale (GCS) <9 (P<0.001), focal neurological deficits (P = 0.05), the presence of a mass effect (P<0.001), and the need for decompressive hemicraniectomy (P<0.001) were associated with poor outcomes. Age, gender, diagnostic delay, seizures at onset, papilledema, parenchymal lesions, deep sinus involvement, and multiple sinus thrombosis were not associated with a poor outcome. Conclusion: In our study, early diagnosis and treatment of CVST is associated with an overall favorable outcome even in the presence of traditional poor prognostic factors such as age, seizures at onset, deep sinus involvement, and multiple sinus involvement in the face of conventional risk factors. A large country-wide prospective study might help in elucidating the poor prognostic factors.

Evaluating Diagnostic Accuracy and Inter-reader Agreement of the Prostate Imaging After Focal Ablation Scoring System.

Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen's kappa (κ), and the system's efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

Near-infrared photoimmunotherapy targeting Nectin-4 in a preclinical model of bladder cancer.

Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) that targets Nectin-4, has shown promising results in the treatment of bladder cancer. However, multiple resistance mechanisms that are unique to ADCs limit the therapeutic potential of EV in clinical practice. Here, we developed and tested a Nectin-4-targeted near-infrared photoimmunotherapy (NIR-PIT) that utilizes the same target as EV but utilizes a distinct cytotoxic and immunotherapeutic pathway in preclinical models of bladder cancer. NIR-PIT was effective in vitro against luminal subtype human bladder cancer cell lines (RT4, RT112, MGH-U3, SW780, and HT1376-luc), but not against other subtype cell lines (UMUC3 and T24). In vivo, the tumor site was clearly visible by Nectin-4-IR700 fluorescence 24 h after its administration, suggesting the potential as an intraoperative imaging modality. NIR-PIT significantly suppressed tumor growth and prolonged survival in SW780 and RT112 xenograft models. Weekly treatment with NIR-PIT further improved tumor control in RT112 xenograft models. The effectiveness of NIR-PIT was also confirmed in HT1376-luc orthotopic xenograft models. Histological analysis verified that NIR-PIT induced a significant pathologic response. Taken together, Nectin-4-targeted NIR-PIT shows promise as a treatment for luminal subtype bladder cancers.