Department of Urology

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1021. VP22 Mediates Tumor Vasculature Specific Targeting
(Elsevier, 2004-05-01) Raikwar, Sudhanshu P.; Gardner, Thomas A.; Kao, Chinghai; Urology, School of Medicine
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 Medicine
We 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.
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 Medicine
Introduction: 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.
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 Medicine
There 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.
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 Medicine
Bladder 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.
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 Medicine
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 Medicine
Kidney 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.
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 Medicine
Introduction 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.
Accuracy of Daily Fluid Intake Measurements Using a "Smart" Water Bottle
(Springer, 2017) Borofsky, Michael S.; Dauw, Casey A.; York, Nadya; Terry, Colin; Lingeman, James E.; Urology, School of Medicine
High fluid intake is an effective preventative strategy against recurrent kidney stones but is known to be challenging to achieve. Recently, a smart water bottle (Hidrate Spark™, Minneapolis, MN) was developed as a non-invasive fluid intake monitoring system. This device could help patients who form stones from low urine volume achieve sustainable improvements in hydration, but has yet to be validated in a clinical setting. Hidrate Spark™ uses capacitive touch sensing via an internal sensor. It calculates volume measurements by detecting changes in water level and sends data wirelessly to users’ smartphones through an application. A pilot study was conducted to assess accuracy of measured fluid intake over 24 h periods when used in a real life setting. Subjects were provided smart bottles and given short tutorials on their use. Accuracy was determined by comparing 24-h fluid intake measurements calculated through the smart bottle via sensor to standard volume measurements calculated by the patient from hand over the same 24 h period. Eight subjects performed sixty-two 24-h measurements (range 4–14). Mean hand measurement was 57.2 oz/1692 mL (21–96 oz/621–2839 mL). Corresponding mean smart bottle measurement underestimated true fluid intake by 0.5 ozs. (95% CI −1.9, 0.9). Percent difference between hand and smart bottle measurements was 0.0% (95% CI − 3%, 3%). Intraclass correlation coefficient (ICC), calculated to assess consistency between hand measures and bottle measures, was 0.97 (0.95, 0.98) indicating an extremely high consistency between measures. 24-h fluid intake measurements from a novel fluid monitoring system (Hidrate Spark™) are accurate to within 3%. Such technology may be useful as a behavioral aide and/or research tool particularly among recurrent stone formers with low urinary volume.
Addition of Sodium Bicarbonate to Irrigation Solution May Assist in Dissolution of Uric Acid Fragments During Ureteroscopy
(Liebert, 2018) Paonessa, Jessica E.; Williams, James C., Jr.; Lingeman, James E.; Urology, School of Medicine
Introduction: We hypothesized that adding sodium bicarbonate (bicarb) to normal saline (NS) irrigation during ureteroscopy in patients with uric acid (UA) nephrolithiasis may assist in dissolving small stone fragments produced during laser lithotripsy. In vitro testing was performed to determine whether dissolution of UA fragments could be accomplished within 1 hour. Materials and Methods: In total 100% UA renal calculi were fragmented, filtered, and separated by size. Fragment sizes were <0.5 mm and 0.5 to 1 mm. Similar amounts of stone material were agitated in solution at room temperature. Four solutions were tested (NS, NS +1 ampule bicarb/L, NS +2, NS +3). Both groups were filtered to remove solutions after fixed periods. Filtered specimens were dried and weighed. Fragment dissolution rates were calculated as percent removed per hour. Additional testing was performed to determine whether increasing the temperature of solution affected dissolution rates. Results: For fragments <0.5 mm, adding 2 or 3 bicarb ampules/L NS produced a dissolution rate averaging 91% ± 29% per hour. This rate averaged 226% faster than NS alone. With fragments 0.5 to 1 mm, addition of 2 or 3 bicarb ampules/L NS yielded a dissolution rate averaging 22% ± 7% per hour, which was nearly five times higher than NS alone. There was a trend for an increase in mean dissolution rate with higher temperature but this increase was not significant (p = 0.30). Conclusions: The addition of bicarbonate to NS more than doubles the dissolution rate of UA stone fragments and fragments less than 0.5 mm can be completely dissolved within 1 hour. Addition of bicarb to NS irrigation is a simple and inexpensive approach that may assist in the dissolution of UA fragments produced during ureteroscopic laser lithotripsy. Further studies are needed to determine whether a clinical benefit exists.

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