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Item 1021. VP22 Mediates Tumor Vasculature Specific Targeting(Elsevier, 2004-05-01) Raikwar, Sudhanshu P.; Gardner, Thomas A.; Kao, Chinghai; Urology, School of MedicineItem A Call to Action to Review the USPSTF's Recommendation for Testicular Self-Examination(Sage, 2022) Rovito, Michael J.; Allen, Keri; Nangia, Ajay; Craycraft, Mike; Cary, Clint; Lutz, Michael; Lyon, Timothy; Fadich, Ana; Baird, Bryce; Welch, Morgan Garrett; Alcantara, Alexie; Urology, School of MedicineWe urge the United States Preventive Services Task Force (USPSTF) to call for a formal review of the evidence regarding testicular self-examination (TSE). Twelve years have since passed since the evidence was last formally analyzed where normally re-reviews occur in 5-year cycles. If they would decide to move forward with this action, we ask for the USPSTF to review their methods for establishing recommendations to optimize their rating system operationalization process. Finally, emerging evidence demonstrates a net positive effect of TSE. This stands in contrast to the assertions of TSE's supposed harm that is prevalent in the literature as well as the rationale behind the USPSTF's "D" rating of TSE.Item A Cost Comparison of Holmium Laser Enucleation of the Prostate with and without Moses(American Urological Association, 2021) Lee, Matthew S.; Assmus, Mark; Agarwal, Deepak; Large, Tim; Krambeck, Amy; Urology, School of MedicineIntroduction: Holmium laser enucleation of the prostate (HoLEP) is a size-independent treatment option for the treatment of benign prostatic hyperplasia. HoLEP has been shown to have excellent improvements in prostate symptom scores and maximum flow rates that have been durable for 2 decades. However, the steep learning curve associated with HoLEP has prevented its widespread adoption. New advancements in lasers, specifically the Moses™ pulse-modulation technology, have resulted in improvements in hemostasis and achieving same-day discharges and catheter removals. We aimed to perform a cost-comparison to analyze if Moses-augmented HoLEP (m-HoLEP) resulted in cost-savings. Methods: A retrospective review was performed of a single expert surgeon's experience from May 2018 to November 2020, comparing m-HoLEP with HoLEP. Perioperative and postoperative variables were abstracted from the medical record. Univariate and multivariate analyses were performed using SAS® 9.4. Two-sided significance was set at p <0.05. Results: A total of 312 men underwent HoLEP during the study period (192 in m-HoLEP group and 120 in HoLEP group). The m-HoLEP group had more same-day discharges (p <0.001) and emergency department visits (6.3% vs 1.7%, p=0.0071). m-HoLEP resulted in hospital cost savings of $840 for the initial surgical episode (p=0.0297). When factoring in emergency department visits/readmissions, the cost savings decreased to $747 per case (p=0.0574). Conclusions: m-HoLEP was associated with same-day discharge and hospital cost savings of $840 for the initial surgical episode. Further study in other institutions with surgeons of varying experience levels will need to be performed to see if these findings can be replicated.Item A Cross-Sectional Analysis of Testicular Cancer Symptom Recognition and Stage of Diagnosis(Sage, 2022) Rovito, Michael J.; Craycraft, Mike; Adams, Wesley B.; Maresca, Michael; Saab, Mohamad M.; Cary, Clint; Gooljar, Chayna; Martinez, Sydney; Zanet, Rama Abu; Urology, School of MedicineThere is a need to further explore the relationship between atypical symptom reporting and stage diagnosis to help develop a clearer defined list of possible testicular cancer (TC) symptoms that could assist physicians diagnose the disease earlier. A cross-sectional study was employed to explore possible associations between TC symptom presentation and stage of diagnosis. An original 40-item survey was distributed among 698 TC survivors to determine the potential impact of several risk factors, experiences, and behaviors upon diagnosis. This analysis aimed to explore how certain patient-driven experiences (e.g., symptoms, perceptions, and behaviors) could serve as catalysts for seeking medical care for testicular health concerns. Experiencing hot flashes or having no symptoms had a positive association with later-stage diagnosis while change in shape had a significant negative association with later-stage diagnosis. While the logistic regression model explained relatively low variance in the data (R2 = .1415), it was statistically significant (χ2p < .001). Pain (odds ratio [OR] = 1.6524, p < .05), hot flashes (OR = 5.7893, p < .01), and no symptoms experienced (OR = 12.4836, p < .01) were all significant predictors of a more advanced stage diagnosis. The concern around uncommon/atypical symptoms are that they are indistinct and do not serve as clear signs that TC is present. However, perhaps in tandem with other more overt symptoms, their discovery can serve in a more confirmatory role for a suspect case. If observed with other uncommonly reported symptoms, these uncommon symptoms could provide another pathway in the TC diagnostic process. Clinical and patient education is warranted to increase awareness of uncommon TC symptoms.Item A novel, safe, fast and efficient treatment for Her2-positive and negative bladder cancer utilizing an EGF-anthrax toxin chimera(Wiley, 2020) Jack, Sherwin; Madhivanan, Kayalvizhi; Ramadesika, Swetha; Subramanian, Sneha; Edwards, Daniel F., II; Elzey, Bennett D.; Dhawan, Deepika; McCluskey, Andrew; Kischuk, Erin M.; Loftis, Alexander R.; Truex, Nicholas; Santos, Michael; Lu, Mike; Rabideau, Amy; Pentelute, Bradley; Collier, John; Kaimakliotis, Hristos; Koch, Michael; Ratliff, Timothy L.; Knapp, Deborah W.; Aguilar, Ruben C.; Urology, School of MedicineBladder cancer is the sixth most common cancer in the United States, and it exhibits an alarming 70% recurrence rate. Thus, the development of more efficient antibladder cancer approaches is a high priority. Accordingly, this work provides the basis for a transformative anticancer strategy that takes advantage of the unique characteristics of the bladder. Unlike mucin-shielded normal bladder cells, cancer cells are exposed to the bladder lumen and overexpress EGFR. Therefore, we used an EGF-conjugated anthrax toxin that after targeting EGFR was internalized and triggered apoptosis in exposed bladder cancer cells. This unique agent presented advantages over other EGF-based technologies and other toxin-derivatives. In contrast to known agents, this EGF-toxin conjugate promoted its own uptake via receptor microclustering even in the presence of Her2 and induced cell death with a LC50 < 1 nM. Furthermore, our data showed that exposures as short as ≈3 min were enough to commit human (T24), mouse (MB49) and canine (primary) bladder cancer cells to apoptosis. Exposure of tumor-free mice and dogs with the agent resulted in no toxicity. In addition, the EGF-toxin was able to eliminate cells from human patient tumor samples. Importantly, the administration of EGF-toxin to dogs with spontaneous bladder cancer, who had failed or were not eligible for other therapies, resulted in ~30% average tumor reduction after one treatment cycle. Because of its in vitro and in vivo high efficiency, fast action (reducing treatment time from hours to minutes) and safety, we propose that this EGF–anthrax toxin conjugate provides the basis for new, transformative approaches against bladder cancer.Item A review of the literature and proposed algorithm for penile fracture management(Oxford, 2024-01) Hardesty, Juliet; Burns, Ramzy T.; Soyster, Mary E.; Mellon, Matthew; Bernie, Helen L.; Urology, School of MedicineIntroduction In the management of penile fractures, immediate surgical repair has resulted in better outcomes when compared with a conservative approach; however, there is currently no consensus on the treatment of patients presenting beyond the immediate period (>24 hours) following injury. Objectives To examine the latest literature on management strategies in penile fracture and propose an optimal algorithm for the treatment of patients with delayed presentation. Methods A comprehensive search was conducted following the PRISMA-P 2020 guidelines. A search was performed in several databases with the following strategy: (“Penile fracture” OR “fracture of penis” OR “rupture of corpora cavernosa” OR “rupture of tunica albuginea”) AND (management OR treatment OR surgery OR “surgical reconstruction” OR “surgical repair”). This resulted in 108 relevant articles. Two independent reviewers screened these articles according to the inclusion criteria. Full-text review of 56 articles was performed, and ultimately 20 studies were selected. Measures included the use of diagnostic imaging, timing of surgical repair (immediate, <24 hours after injury; delayed, >24 hours), surgical approach, and long-term complications (ie, erectile dysfunction and penile curvature). Results The review highlighted the benefits of immediate surgical repair in penile fractures, demonstrating improved patient outcomes. Furthermore, it found that surgical repair should be considered even in cases with delayed presentation (>24 hours after injury). To better evaluate the long-term impact of delayed surgical intervention on patient outcomes, we recommend standardized postoperative follow-up, with routine assessments of erectile function and penile curvature. Conclusion Contemporary literature suggests that immediate and delayed surgical repair of penile fractures leads to adequate postoperative outcomes, and patients presenting >24 hours after injury should still be considered for surgery.Item A Simplified Diagnostic Approach on TFE3 Gene Fusion-Associated Renal Cell Carcinoma(Allen Press, 2020-11-04) Akgul, Mahmut; Cheng, Liang; Idrees, Muhammad; Urology, School of MedicineItem A single-institution experience with the Optilume Urethral Drug Coated Balloon for management of urethral stricture disease(AME, 2024) Mahenthiran, Ashorne K.; Burns, Ramzy T.; Soyster, Mary E.; Black, Morgan; Arnold, Peter J.; Love, Harrison L.; Mellon, Matthew J.; Urology, School of MedicineBackground: Urethral stricture disease is detrimental to quality of life. The Optilume Urethral Drug Coated Balloon (DCB) offers a solution utilizing a paclitaxel-coated balloon to expand strictures and prevent recurrence. Following the ROBUST trials, it has been proposed that DCB is more effective than conventional endoscopic management for recurrent, small anterior urethral strictures. Our study provides insights into practical applications and outcomes using DCB for urethral stricture disease. Methods: A retrospective review was performed of patients who underwent DCB for urethral strictures at our institution from November 2022 to August 2023 with follow-up evaluated through January 2024. Demographics, stricture characteristics, operative details, and postoperative outcomes were collected. Primary endpoint was need for repeat intervention as determined by symptomatic burden and subsequently postoperative post-void residual if obtained. Secondary endpoint was complication rate. Statistical analysis was conducted using STATA/BE17.0 software to create Kaplan-Meier curves for time to repeat intervention after treatment with DCB. Results: Of 43 patients, 16 had no prior treatment. The other 27 had endoscopic treatment and of this group, 11 also had additional urethroplasty. Stricture etiologies included 20 iatrogenic, 14 idiopathic, 5 radiation-related, 2 inflammatory, and 2 traumatic. Stricture locations were 2 fossa navicularis, 7 pendulous, 17 bulbar, 7 membranous, 3 prostatic, and 7 bladder neck contractures. Mean balloon dilation lasted 8.4±2.7 minutes. All patients had a minimum follow-up of 150 days postoperatively and the mean duration of follow-up for the cohort was 290.3±87.0 days. The average postoperative post-void residual was 33.4±90.6 milliliters. Two patients had immediate complications: 1 with urinary retention after catheter removal requiring suprapubic tube placement and 1 with urinary tract infection requiring antibiotics. Four patients required repeat interventions: 1 endoscopic dilation, 1 graft urethroplasty, and 2 repeat DCB procedures. Mean time to repeat intervention was 203.5±82.6 days, and no patient required repeat intervention within 145 days of initial surgery. Conclusions: DCB offers a safe and less invasive treatment for both treatment-naïve and recurrent urethral strictures with paclitaxel coating to prevent recurrence. Repeat intervention was not required for 90.7% of our cohort within an average follow-up duration of 9 months postoperatively. As DCB grows in clinical use, investigation into its long-term efficacy is justified.Item A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease(Nature, 2023-07-19) Canela, Victor Hugo; Bowen, William S.; Ferreira, Ricardo Melo; Syed, Farooq; Lingeman, James E.; Sabo, Angela R.; Barwinska, Daria; Winfree, Seth; Lake, Blue B.; Cheng, Ying-Hua; Gaut, Joseph P.; Ferkowicz, Michael; LaFavers, Kaice A.; Zhang, Kun; Coe, Fredric L.; Worcester, Elaine; Jain, Sanjay; Eadon, Michael T.; Williams, James C., Jr.; El-Achkar, Tarek M.; Urology, School of MedicineKidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.Item The ability of a limited metabolic assessment to identify pediatric stone formers with metabolic abnormalities(Elsevier, 2018) Chan, Katherine H.; Moser, Elizabeth A.; Whittam, Benjamin M.; Misseri, Rosalia; Cain, Mark P.; Krambeck, Amy; Urology, School of MedicineIntroduction American Urological Association guidelines recommend a urinary metabolic evaluation after the first stone event in all pediatric stone patients. Prior studies identified hypercalciuria and urine hypovolemia as the most common abnormalities in children with urolithiasis. Recent data suggest that hypocitraturia is most prevalent. It was hypothesized that a limited evaluation would detect the majority of clinically significant metabolic abnormalities in pediatric stone formers. Material and methods A retrospective analysis of all children (<18 years of age) with renal/ureteral calculi evaluated at the study institution from 2005 to 2015 was performed. Children with ≥ one 24-h urinary metabolic profile after a clinical visit for renal/ureteral calculi were included. Those with bladder stones and those with undercollection or overcollection or missing urinary creatinine were excluded. Demographics and data from the first urinary metabolic profile and stone analyses were collected. The sensitivity, specificity, and positive and negative predictive value (NPV) of a limited urinary metabolic evaluation consisting of four parameters (24-h calcium, citrate, and oxalate and low urinary volume) were compared to a complete urinary metabolic profile. The number and type of metabolic abnormalities that would have been missed with this limited evaluation weredetermined. Results Of 410 patients, 21 were excluded for age ≥18 years, 13 for bladder stones, 248 for overcollections, 38 for undercollections, and 10 for missing creatinine. This left 80 patients for inclusion: median age 11.4 years, 60% female, and 96.3% white. Of the entire cohort, 69.6% had hypocitraturia, 52.5% had low urine volume, and 22.5% had hypercalciuria. Sensitivity was 87.5%. Specificity could not be calculated because no patients had a normal complete metabolic evaluation. The NPV was zero, and the positive predictive value was 100%, but these are artifacts resulting from the absence of patients with a normal complete metabolic evaluation. Of the 80 patients, 10 had at least one abnormality missed by a limited metabolic evaluation (Table 1). The missed abnormalities were high pH (n = 6), abnormal 24-h phosphorus (low in 1 patient and high in 1 patient), low 24-h magnesium (n = 3), low 24-h potassium (n = 3), and high 24-h sodium (n = 4). Discussion A limited urinary metabolic evaluation would have detected the vast majority of clinically significant metabolic abnormalities in the study sample. Approximately two-thirds of the study patients submitted inadequate 24-h urine specimens. Conclusions A simplified approach to metabolic evaluation in first-time stone formers with a stone analysis available was proposed. This streamlined approach could simplify the metabolic evaluation and reduce health care costs.