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Item The orchestration of gene expression and the editing role of microRNA(Elsevier, 2023-06) Fossum, M.; Kaefer, M.; Herbst, K. W.; Harper, L.; Beckers, G. M. A.; Nelson, C. P.; Garriboli, M.; Nieuwhof-Leppink, A.; Bagli, D.; Kalfa, N.; ESPU Research Committee; Urology, School of MedicineIn this short educational communication the ESPU Research Committee presents the role of non-coding RNA and how these can affect gene expression. In particular we discuss the role of microRNA on post transcriptional changes and how these may cause pathological conditions within Pediatric Urology and how microRNA could be useful in future clinical practice.Item Optimal management of testicular cancer: from self-examination to treatment of advanced disease(Dove Press, 2010-08-12) Beck, Stephen D. W.; Urology, School of MedicineGerm-cell cancer is the most common solid tumor in men aged 15 to 35 years and has become the model for curable neoplasm. Over the last 3 decades, the cure rate has increased from 15% to 85%. This improved cure rate has been largely attributed to the introduction of cisplatin-based chemotherapy. In stage I seminoma and nonseminoma, cure rates approach 100% and treatment is governed by patient choice based on the perceived morbidities of each therapy and personal preferences. For seminoma, treatments include surveillance, radiotherapy, and single course carboplatin. For nonseminoma, treatments include surveillance, retroperitoneal lymph node dissection (RPLND), and adjuvant chemotherapy. Low volume (<3 cm) stage II seminoma is typically managed with radiotherapy while higher volume (>3 cm) stage II and stage III disease treated with chemotherapy. Positron emission tomography (PET) imaging can differentiate active cancer versus necrosis for postchemotherapy residual masses. PET-positive masses are managed with either surgery or second-line chemotherapy. Low volume (<5 cm) stage II nonseminoma with normal serum tumor markers may be managed with either RPLND or chemotherapy. Patients with persistently elevated serum tumor markers and larger volume stage II and stage III disease are managed with systemic chemotherapy. As with seminoma, good risk patients are typically treated with 3 courses of bleomycin, etoposide, and cisplatin (BEP) and intermediate and poor risk patients are treated with 4 courses. Residual postchemotherapy masses should be resected due to the uncertainty of the histology with 50% to 60% harboring residual teratoma or active cancer. The majority of patients completing initial therapy who relapse do so within 2 years. A minority of patients (2%-3%) recur after 2 years and this phenomenon is termed late relapse. Excluding chemonaïve patients, late relapse disease is typically managed surgically with 50% being cured of disease. Current therapeutic challenges in testis cancer include the accurate prediction of postchemotherapy histology to avoid surgery in patients harboring fibrosis only, improved therapy in platinum-resistant and platinum-refractory disease, and the understanding of the biology of late relapse.Item Advances in Robotic-Assisted Radical Prostatectomy over Time(Hindawi, 2013) Jacobs, Emma F. P.; Boris, Ronald; Masterson, Timothy A.; Urology, School of MedicineSince the introduction of robot-assisted radical prostatectomy (RALP), robotics has become increasingly more commonplace in the armamentarium of the urologic surgeon. Robotic utilization has exploded across surgical disciplines well beyond the fields of urology and prostate surgery. The literature detailing technical steps, comparison of large surgical series, and even robotically focused randomized control trials are available for review. RALP, the first robot-assisted surgical procedure to achieve widespread use, has recently become the primary approach for the surgical management of localized prostate cancer. As a result, surgeons are constantly trying to refine and improve upon current technical aspects of the operation. Recent areas of published modifications include bladder neck anastomosis and reconstruction, bladder drainage, nerve sparing approaches and techniques, and perioperative and postoperative management including penile rehabilitation. In this review, we summarize recent advances in perioperative management and surgical technique for RALP.Item What are validated questionnaires and which ones measure quality of life?(Elsevier, 2023-08) Szymanski, Konrad M.; Kaefer, Martin; Fossum, Magdalena; Kalfa, Nicolas; Herbst, Kathy; Braga, Luis H.; Cascio, Salvatore; Garriboli, Massimo; Nelson, Caleb P.; Nieuwhoff-Leppink, Anka; Bagli, Darius; Harper, Luke; ESPU Research Committee; Urology, School of MedicineItem Risk of residual cancer after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumour and International Germ Cell Cancer Cooperative Group intermediate/poor prognosis: A multi-institutional retrospective cohort study(Elsevier, 2023-03) Antonelli, Luca; Ardizzone, Davide; Ravi, Praful; Bagrodia, Aditya; Mego, Michal; Daneshmand, Siamak; Nicolai, Nicola; Nazzani, Sebastiano; Giannatempo, Patrizia; Franza, Andrea; Heidenreich, Axel; Paffenholz, Pia; Saoud, Ragheed; Eggener, Scott; Ho, Matthew; Oswald, Nathaniel; Olson, Kathleen; Tryakin, Alexey; Fedyanin, Mikhail; Naoun, Natacha; Javaud, Christophe; Fizazi, Karim; King, Jennifer M.; Adra, Nabil; Douglawi, Antoin; Cary, Clint; Sweeney, Christopher; Fankhauser, Christian D.; Urology, School of MedicineIntroduction Current guidelines recommend surveillance in metastatic non-seminomatous germ cell tumour patients treated with first-line-chemotherapy and a complete clinical response (normalisation of serum tumour markers and residual masses <1 cm). However, this recommendation is based on a series including patients with good prognosis according to International Germ Cell Cancer Cooperative Group prognostic group (IGCCCG-PG). The aim of this study was to analyse the proportion of residual teratoma and survival among patients with intermediate/poor IGCCCG-PG and a complete clinical response after first-line-chemotherapy. Material & methods This is a retrospective study of men with intermediate/poor IGCCCG-PG, who had a complete clinical response after first-line chemotherapy. Patients were either followed by surveillance or treated with post-chemotherapy retroperitoneal lymph node dissection (pcRPLND). Results Between 2009 and 2018, 143 men with intermediate (n = 83) or poor (n = 60) IGCCCG-PG were treated at 11 international centres. Among 33 patients treated with pcRPLND, the specimen showed teratoma and viable cancer in 16 (48%) and 4 (12%). During a median a 7-year follow-up, 20/110 (18%) patients managed with surveillance relapsed, of whom seven (6%) had a retroperitoneal-only relapse versus 2/33 patients managed with pcRPLND relapsed. No difference was observed regarding overall survival (OS) among men treated with pcRPLND or surveillance (5-year OS, 93% and 89%, p-value = 0.35). The median time-to-recurrence among men on surveillance was 1.3 years (range: 0.3–9.1), and the most common sites of relapses included retroperitoneum (11%), chest (5%), and bones (4%). Conclusions While most men with intermediate/poor IGCCCG-PG harbour teratoma/cancer in the retroperitoneum despite a complete response to first-line-chemotherapy, only 6% managed with surveillance relapsed in the retroperitoneum. There was no significant difference in OS between the two groups.Item Increased oscillation rate may improve morcellation efficiency in HoLEP(Canadian Urological Association, 2025) McClaine, Cameron; Shelton, Thomas M.; Slade, Austen; Adeola, Andrew; Rivera, Marcelino E.; Urology, School of MedicineIntroduction: Tissue morcellation has become increasingly efficient, yet remains a rate-limiting step in holmium enucleation of the prostate (HoLEP). Limited data exists on how the rate of oscillation by the morcellator blades affects morcellation efficiency (ME). Methods: We undertook a retrospective review of HoLEP procedures performed by two surgeons from July 1, 2019, to August 25, 2022. All morcellation was performed with the Wolf Piranha device and enucleation was performed with Moses 2.0 technology. Surgeon 1 routinely uses 1500 oscillations/min (low rate [LR]) and surgeon 2 uses a rate of 6000 oscillations/min (high rate [HR]). These rates were confirmed upon electronic medical record review of each case. The primary endpoint was ME (g/minute). Secondary endpoints included enucleation efficiency (EE), mean tissue specimen weight, and preoperative prostate volume. Results: A total of 894 HoLEPs were analyzed, 592 by surgeon 1 and 302 by surgeon 2. Surgeon 1 had larger preoperative prostate volumes (126 vs. 101, p<0.001) and specimen tissue weights (86.0 vs. 61.1, p<0.001). EE was higher in the LR group (1.67 vs. 1.33 g/min, p<0.001). Morcellation time was longer in the LR group (11.3 vs. 6.09 min, p<0.001) and ME was lower in the LR group (9.26 vs. 12.1 g/min, p<0.001). The difference in ME was inversely proportional to specimen weight. Conclusions: Increased oscillation rate during morcellation may lead to decrease in morcellation time and increased ME during prostate enucleation. The primary limitation of this paper is the inclusion of only two surgeons. Future studies will serve to evaluate this finding across a larger number of institutions, and evaluate ways to increase ME in large prostate cohorts.Item Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system(Sage, 2014-01-21) Liu, Li-Yu D.; Chang, Li-Yun; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Lin, Yi-Shing; Jeng, Meei-Huey; Roth, Don A.; Chang, King-Jen; Hsieh, Fon-Jou; Urology, School of MedicineThe aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.Item Is There an Association between Childhood Obesity and Pediatric Kidney Stone Disease? A Literature Review(MDPI, 2021) Paiste, Henry J.; Moradi, Luke; Assimos, Dean G.; Wood, Kyle D.; Dangle, Pankaj P.; Urology, School of MedicineObjectives: To examine the most recent literature and published science in determining any and all possible associations between pediatric obesity and pediatric urolithiasis. Methods: Retrospective literature review of pediatric stone formers with diagnosed stone disease and all associated risk factors. Peer-reviewed, published manuscripts from the past several decades were analyzed for risk factors associated with pediatric obesity such as diet, hypertension, and renal diseases. Comparing the pediatric obesity literature with the pediatric stone forming literature, any associations and correlations were derived and analyzed. Results: Despite the existing evidence that obesity is linked to stones in adults, the evidence remains unclear whether obesity plays a role in children. Nutritional discrepancies, in the setting of the obesity epidemic, have been shown to alter the risk profile of pediatric patients. Consistent with the published literature, and lack of consistent correlation with obesity and stone disease, is the knowledge that age, gender, geography, and climate may all play a role in the onset of pediatric obesity and may also be on the causal pathway toward pediatric urolithiasis. Conclusion: The manuscript demonstrates that there are a number of risk factors, congenital or acquired, that are associated with pediatric obesity. The mechanisms responsible for these associations may be on the causal pathway toward childhood urolithiasis. These mechanisms that underlie these associations need to be further investigated.Item Holmium Laser Enucleation of the Prostate Efficiency by Prostate Gland Size: Is There a Sweet Spot?(MDPI, 2021) Assmus, Mark Alexander; Large, Tim; Krambeck, Amy; Urology, School of MedicineHolmium laser enucleation of the prostate (HoLEP) is one of only two AUA guideline-recommended prostate size-independent surgeries for benign prostate hyperplasia (BPH). The significant variation in gland size treated results in a wide range of enucleation and morcellation times. We sought to understand the effect of prostate size on HoLEP efficiency to better educate patients and improve operative room utilization. After IRB approval, we identified patients from 1 July 2016 to 1 January 2020 who underwent HoLEP by two endourologists. Our primary objectives were to assess the effects of increasing increments (25 g) of mean enucleated prostate tissue weight on enucleation and morcellation efficiency (g/min). One-way Kruskal–Wallis ANOVA with Dunn’s post hoc test was used, with significant p < 0.05. We included 675 HoLEPs with all comers mean tissue weight resected of 72.1 g (Range 1–448 g), energy used 110.00 kJ (10.73–340 kJ), enucleation time 48.6 min (5–151 min), and morcellation time 10.1 min (0.5–113 min). Average enucleation efficiency increased with increasing prostate size categories (e.g., <25 g–0.48 g/min, >325 g–3.91 g/min) (K-W ANOVA p = 0.004, Dunn’s post hoc p = 0.004). The combined average enucleation and morcellation efficiency was ≥5 g/min between 55 and 271 g. Inefficiency for cases <55 g was driven by enucleation, while >271 g case inefficiency was driven by morcellation. Increasing tissue weight at the time of HoLEP is associated with a linear relationship of increasing enucleation and decreasing morcellation efficiencies.Item Analgesic Efficacy of Quadratus Lumborum Block in Infants Undergoing Pyeloplasty(MDPI, 2021) Chisolm, Paul F.; Singh, Nikhi P.; Cummins, Ian; Oster, Robert A.; Cox, Damon; Dangle, Pankaj P.; Urology, School of MedicinePost-operative analgesic management is challenging in infants and opioids have been the standard of care. However, they are associated with adverse effects which may negatively impact infants. In this retrospective cohort study, we sought to explore the postoperative analgesic efficacy of quadratus lumborum (QL) block in the infant population undergoing dorsal lumbotomy pyeloplasty. Chart review of 34 infants (≤12 months) who underwent dorsal lumbotomy pyeloplasty between 2016–2020 was performed. Post-operative pain was assessed using externally validated pain scales (CRIES & FLACC) and monitored hemodynamics (pulse and blood pressure). Opioid doses were standardized by using morphine milligram equivalency (MME). The Prescription Database Monitoring Program (PDMP) was utilized to determine if discharge opioid prescriptions were filled. Of 34 patients, 13 received the QL block. Mean age at the time of surgery was 6.2 months ± 3.2 months. The QL group received 0.8 MME postoperatively, whereas the non-QL group received 0.9 MME (p = 0.82). The QL group (20%) filled their discharge opioid prescription less frequently compared to non-QL group (100%) (p = 0.002). There were no observed differences between pain scale or hemodynamic variables. Further studies are warranted to explore QL block’s efficacy for post-operative infant pain management.