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Background: Prostate cancer is the most common solid-organ malignancy in adult men. Early detection and treatment of prostate cancer with radical prostatectomy (RP) has improved cancer-specific survival but is associated with penile shortening and erectile dysfunction. Penile traction therapy (PTT) has been demonstrated to increase stretched penile length (SPL) prior to penile prosthesis placement and may improve erectile function (EF) in patients with Peyronie's disease. We aimed to evaluate the efficacy of PTT in preserving penile length and EF after bilateral cavernous nerve crush injury (BCNI) in a rat model., Methods: Twenty-four male Sprague-Dawley rats aged 11-13 weeks were randomly assigned to three groups (n=8, each): sham operation with no PTT (Sham), BCNI without PTT (Crush), and BCNI with PTT (Traction). PTT was started on postoperative day 3. A traction force of 1 Newton was applied to the penis for 30 minutes each day for 28 days. After 28 days of traction, the cavernous nerve was stimulated while recording the intracavernosal pressure (ICP) and the mean arterial pressure (MAP) simultaneously. Cavernosal tissue was excised, and western blot analysis for endothelial nitric oxide synthase (eNOS) was performed. Significance was determined by using ANOVA with Tukey-Kruger post-hoc testing., Results: At 4 weeks after nerve injury, the Traction group had significantly greater SPL compared to the Sham and Crush groups (30 vs. 28 and 27 mm, respectively). The Sham group had significantly greater EF (ΔICP/MAP) compared to the Crush group at 2.5, 5, and 7.5 V. The EF of the Traction group was between that of the Sham and Crush groups and was not significantly different from the Sham group at any voltages. Further downstream analysis revealed that the Traction group had significantly greater eNOS expression in cavernosal tissue compared to the Crush group, which was confirmed on western blot analysis and immunohistochemistry (IHC) staining., Conclusions: Findings from this animal study suggest that PTT has the potential to mitigate penile retraction after RP. While more studies are needed to determine the effect of PTT on preservation of EF, the increased eNOS expression observed in the Traction group offers a potential protective mechanism of action., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-53/coif). BD reports has received a grant to fund this project from the Sexual Medicine Society of North America. WJGH is an advisor for Coloplast, Boston Scientific, and a speaker for Endo. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Context: Despite the benefits of digital pathology, data storage and management of digital whole slide images introduces new logistical and infrastructure challenges to traditionally analog pathology labs., Aims: Our goal was to analyze pathologist slide diagnosis patterns to determine the minimum number of pixels required during the diagnosis., Methods: We developed a method of using pathologist viewing patterns to vary digital image resolution across virtual slides, which we call variable resolution images. An additional pathologist reviewed the variable resolution images to determine if diagnoses could still be rendered., Results: Across all slides, the pathologists rarely zoomed in to the full resolution level. As a result, the variable resolution images are significantly smaller than the original whole slide images. Despite the reduction in image sizes, the final pathologist reviewer could still proide diagnoses on the variable resolution slide images., Conclusions: Future studies will be conducted to understand variability in resolution requirements between and within pathologists. These findings have the potential to dramatically reduce the data storage requirements of high-resolution whole slide images., (© 2022 The Authors.)

To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 51.5% of cases; of these, 48.6% had the T1a/b stage. Analysis showed upregulation of miR-221-3p and miR-222-3p and downregulation of miR-204-5p in 68 paired cancer tissues ( p < 0.001). These three miRNAs were not differentially expressed in RAI and non-RAI groups. The ATA risk score showed poor discriminative ability (AUC = 0.518, p = 0.80). In contrast, the microRNA-based risk score showed high accuracy in predicting tumor progression in the whole cohorts (median = 1.87 vs. 0.39, AUC = 0.944) and RAI group (2.23 vs. 0.37, AUC = 0.979) at the cutoff >0.86 (92.6% accuracy, 88.6% sensitivity, 97% specificity) in the whole cohorts (C-statistics = 0.943/Brier = 0.083) and RAI subgroup (C-statistic = 0.978/Brier = 0.049). The high-score group had a three-fold increased progression risk (hazard ratio = 2.71, 95%CI = 1.86-3.96, p < 0.001) and shorter survival times (17.3 vs. 70.79 months, p < 0.001). Our prognostic microRNA signature and nomogram showed excellent predictive accuracy for progression-free survival in DTC.

Background: Accurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer., Methods: The pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables., Results: The CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis [Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10 -6 ] after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10 -21 ). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%)., Conclusions: Both CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.

Background: Better prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain., Objective: To evaluate the utility of both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population., Design, Setting, and Participants: Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. CCP scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components., Intervention: Active treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting., Outcome Measurements and Statistical Analysis: The primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests., Results and Limitations: The final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p<0.001), and there was no interaction with ancestry (p=0.20) or treatment (p=0.09). The CCR score was highly prognostic (HR 3.86; p<0.001), and as with the CCP score, there was no interaction with ancestry (p=0.24) or treatment (p=0.32). Limitations include the retrospective study design and the use of self-reported ancestry information., Conclusions: A CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables., Patient Summary: In this study we evaluated the ability of a combined molecular and clinical score to predict the progression of localized prostate cancer. We found that the combined molecular and clinical score predicted progression to metastasis regardless of patient ancestry or treatment. This suggests that the combined molecular and clinical score may be a valuable tool for determining the risk of metastasis in men with newly diagnosed prostate cancer in order to make appropriate treatment decisions., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph node stromal cells (HK cells). Mice were monitored weekly with bioluminescence imaging to assess tumor growth and metastasis. Primary tumors and organs were harvested for bioluminescence imaging, weight, and formalin-fixed for hematoxylin and eosin and immunohistochemistry staining. In this patient-derived orthotopic xenograft model, xenograft tumors showed better implantation rates than currently reported using other models. Xenograft tumors histologically resembled pre-implanted primary specimens from patients, presenting muscle-invasive growth patterns. In the presence of HK cells, tumor formation, tumor angiogenesis, and distant organ metastasis were significantly enhanced in both UM-UC-3 cells and patient-derived specimens. Thus, we established a unique, reproducible patient-derived orthotopic xenograft model using human high-grade urothelial cell carcinoma cells and lymph node stromal cells. It allows for investigating the mechanism involved in tumor formation and metastasis, and therefore it is useful for future testing the optimal sequence of conventional drugs or the efficacy of novel therapeutic drugs., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Multilocular cystic renal cell carcinoma (RCC) is an uncommon renal neoplasm composed of thin fibrous septa lining multiple cystic spaces and associated with an excellent prognosis. Clear cells with generally low-grade nuclear features line the cystic spaces and may be present within the fibrous septa, although solid mass-forming areas are by definition absent. Despite the excellent prognosis, molecular-genetic alterations are similar to those of clear cell RCC. Immunohistochemical staining characteristics, however, have not been well elucidated. We studied 24 cases of multilocular cystic RCC, classified according to the 2004 World Health Organization System. Immunohistochemical analysis was performed using an automated immunostainer for CD10, cytokeratin 7 (CK7), α-methylacyl-CoA-racemase, epithelial membrane antigen (EMA), cytokeratin CAM 5.2, carbonic anhydrase IX (CA-IX), estrogen/progesterone receptors, smooth muscle actin, PAX-2, and vimentin. Twenty-four cases of grade 1 to 2 clear cell RCC were stained for comparison. Multilocular cystic RCC and control cases of clear cell RCC showed the following results, respectively: CD10 (63%, 96%), CK7 (92%, 38%), α-methylacyl-CoA-racemase (21%, 67%), vimentin (58%, 33%), estrogen receptor (8%, 8%), CAM 5.2 (100%, 96%), EMA, CA-IX, PAX-2 (all 100%), and progesterone receptor (0%). Smooth muscle actin highlighted myofibroblastic cells within the septa of multilocular cystic RCC and the fine capillary vascular network of clear cell RCC. In summary, multilocular cystic RCC showed expression of common clear cell RCC markers CA-IX, EMA, and PAX-2, supporting the hypothesis that multilocular cystic RCC is a subtype of clear cell RCC. In contrast to clear cell RCC, tumors less frequently expressed CD10 (63% and often focal vs. 96% and diffuse) and more frequently expressed CK7 (92%), often diffusely (63%). Coexpression of CA-IX and CK7 represents a point of overlap with the recently described clear cell papillary RCC, which also may show a prominent cystic architecture. However, the latter lacks mutation of the VHL gene and deletion of chromosome 3p by molecular methodologies.

Aims: To evaluate the histological and immunohistochemical characteristics of ectopic prostatic tissue., Methods and Results: We studied 20 cases of ectopic prostate. In 85% (17/20) of the cases, the ectopic prostatic tissue was located in the bladder; in the remaining cases, it was located in the urethra. In 60% of the cases (12/20), no significant inflammatory or reactive/reparative changes were identified in the adjacent tissue. Immunohistochemical stains for prostate-specific antigen, prostate-specific acid phosphatase, and prostein were positive in the glandular epithelial cells of all cases. Stains for 34βE12 and p63 confirmed the presence of basal cells in all cases. There was no overexpression of α-methylacyl-CoA racemase in any of the cases. There was cytoplasmic luminal staining for CD10 and cytoplasmic staining for cytokeratin 18 in acinar cells in all cases. In cases in which followup data were available, no patient was found to have residual or recurrent ectopic prostatic tissue and none developed prostatic adenocarcinoma., Conclusions: Ectopic prostatic tissue is occasionally encountered in the lower urinary tract, most commonly in the bladder and urethra of males. Ectopic prostatic tissue has histological and immunohistochemical characteristics that are indistinguishable from those of normal prostatic tissue, and most likely represents the persistence of embryonic structures., (© 2011 Blackwell Publishing Limited.)

Multilocular cystic renal cell carcinoma is an uncommon low grade renal cell carcinoma with unique morphologic features. Its cytogenetic characteristics have not been fully investigated. Its relationship to typical clear cell renal cell carcinoma is uncertain. We evaluated 19 cases of multilocular cystic renal cell carcinoma diagnosed by strict morphologic criteria using the 2004 WHO classification system. The control group consisted of 19 low grade (Fuhrman grades 1 or 2) clear cell renal cell carcinomas. Chromosome 3p deletion status was determined by dual color interphase fluorescence in situ hybridization analysis. Chromosome 3p deletion was identified in 17 out of 19 (89%) of the clear cell renal cell carcinoma cases and 14 out of 19 (74%) of the multilocular cystic renal cell carcinoma cases, respectively. There was no difference in the status of chromosome 3p deletion between clear cell renal cell carcinoma and multilocular cystic renal cell carcinoma (P=0.40). These results support the concept that multilocular cystic renal cell carcinoma as a subtype of clear cell renal cell carcinoma.

We describe a young patient with acute myeloid leukemia who, having been treated with allogenic hematopoietic stem cell transplantation, presented with acute graft-versus-host disease. One year later, leukemia relapse was treated with donor lymphocyte infusion and was followed by a new episode of acute graft-versus-host disease. The patient died 18 months after the transplantation, with evidence of chronic graft-versus-host disease in multiple organs.