Cellular senescence in testicular cancer. Is there a correlation with the preoperative markers and the extent of the tumor? An experimental study.

PURPOSE: The aim of this experimental study is to investigate the correlation between the presence of senescent cells and the tumor size, the lymphovascular invasion (LVI), the invasion of rete testis (RTI), the preoperative tumor markers or pathological stage in patients who underwent orchiectomy for malignant purposes. METHODS: This experimental study included patients with a history of radical orchiectomy performed from January 2011 to January 2019. The testicular tissue specimens underwent an immunohistopathological process for the detection of the presence of cellular senescence. Besides, the tumor size, the histopathological type, the pathological stage of the tumor and the presence of Lymphovascular (LVI) or rete testis (RTI) invasions were also recorded. Additionally, the preoperative serum levels of alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were recorded. After the completion of immunohistochemical analysis, the rate of senescent cells in each specimen was also recorded. RESULTS: The mean senescent cell rate was estimated to be 14.11±11.32% and 15.46±10.58% in patients with presence of LVI or absence of LVI, respectively (p=0.46). The mean senescent cell rate was calculated at 18.13±12.26% and 12.56±9.38% (p=0.096) in patients with presence of RTI or absence of RTI, respectively. The mean senescent cell rate in the pT1 group was calculated at 14.58 ± 9.82%, while in T2 and T3 groups the mean senescent cell rate was estimated to be 15.22 ± 12.03% and 15.35 ± 14.21%, respectively (p=0.98). A statistically significant correlation was detected between the senescence rate and the tumor size (Pearson score 0.40, p=0.027) and between the rate of senescent cells and the preoperative level of lactate dehydrogenase (LDH) (Pearson score -0.53, p=0.002). CONCLUSIONS: The presence of cellular senescence was correlated with the extent of the testicular tumor in terms of tumor size as well as the preoperative level of the LDH serum marker.

Endoscopic enucleation of the prostate with Thulium Fiber Laser (ThuFLEP). A retrospective single-center study.

PURPOSE: The aim of the present, retrospective study was to describe our initial experience and early outcomes of Thulium Fiber Laser enucleation of the prostate (ThuFLEP) with the use of the FiberDust™ (Quanta System, Samarate, Italy) in patients with benign prostate hyperplasia. METHODS: From June 2022 to April 2023, all patients who underwent endoscopic enucleation of the prostate at Urology Department of the University Hospital of Patras were included. A single surgeon utilizing the same standardized operative technique performed all the surgeries. The primary endpoints included the uneventful completion of the operation, the surgical time and any minor or major complication observed intra- or post-operatively. RESULTS: Twenty patients with benign prostate hyperplasia were treated with ThuFLEP. All the surgeries were completed successfully and uneventfully. The enucleation phase of the operation was completed in a mean time of 45±9.1 min, while the average time needed for the morcellation was 17.65±3.42 min. No significant complications were observed intra- or post-operatively. The average hemoglobin drop was calculated to be 0.94±0.71 g/dL. CONCLUSIONS: All the operations were successfully and efficiently completed with the use of the FiberDust™ (Quanta System, Samarate, Italy) in ThuFLEP. Significant blood loss or major complications were not observed.

Minimal invasive treatment of urethral strictures: An experimental study of the effect of paclitaxel coated balloons in the wall of strictured rabbit's urethra.

PURPOSE: The aim of this study is the evaluation of the distribution of paclitaxel (PTX) released by a coated balloon in the layers of rabbit's urethra. METHODS: 18 rabbits were included. A laser device was used for the stricture formation. After two weeks, dilation of the strictured urethra was performed by using Advance 35LP PTA balloons and Advance 18 PTX PTA balloons. The experimental models were divided into 3 groups. The group Α included two rabbits without any intervention except for the stenosis procedure. Group B compromised six rabbits that underwent dilation with Advance 35LP PTA balloons. Group C consisted of 10 rabbits to which dilation with both Advance 35LP PTA balloons and Advance 18 PTX PTA balloons was applied. Histological evaluation and Immunohistochemistry were performed on all specimens. RESULTS: Inflammation, fibrosis and ruptures were detected in the specimens of the study. In specimens of Group C the decrease of inflammation and fibrosis rate was greater. Anti-PTX antibody was detected in the epithelium, lamina propria and smooth muscle layer of all specimens of urethras that have been harvested immediately and 1 day after the dilation with Advance 18 PTX PTA balloon and it was not observed in any layer of the urethral wall of the rest of the examined specimens of Group C. CONCLUSIONS: PTX's enrichment was detected in the smooth muscle layer of all specimens that have been harvested immediately and 24h after the dilation with Advance 18 PTX PTA balloons. PTX may play an inhibitive role in the recurrence of the stenosis.

Percutaneous antegrade management of large proximal ureteral stones using non-papillary puncture.

Objective: To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy (npPCNL) for the management of large proximal ureteral stones. Methods: We evaluated prospectively collected data of 37 patients with large proximal ureteral stones more than 1.5 cm in diameter treated by prone npPCNL. Depending on stone size, in-toto stone removal or lithotripsy using the Lithoclast® Trilogy (EMS Medical, Nyon, Switzerland) was performed. Perioperative parameters including operative time (from start of puncture to the skin suturing), stone extraction time (from the first insertion of the nephroscope to the extraction of all stone fragments), and the stone-free rate were evaluated. Results: Twenty-one males and 16 females underwent npPCNL for the management of large upper ureteral calculi. The median age and stone size of treated patients were 58 (interquartile range [IQR]: 51-69) years and 19.3 (IQR: 18.0-22.0) mm, respectively. The median operative time and stone extraction time were 25 (IQR: 21-29) min and 8 (IQR: 7-10) min, respectively. One case (2.7%) of postoperative bleeding and two cases (5.4%) of prolonged fever were managed conservatively. The stone-free rate at a 1-month follow-up was 94.6%. Conclusion: The npPCNL provides a straight route to the ureteropelvic junction and proximal ureter. Approaching from a dilated portion of the ureter under low irrigation pressure with larger diameter instruments results in effective and safe stone extraction within a few minutes.

How long do we need to reach sufficient expertise with the avatera® robotic system?

PURPOSE: To investigate the learning curve in four basic surgical skills in laparoscopic and robotic surgeries, and evaluate the approximate time needed to reach sufficient expertise in performing these tasks with the avatera® system. METHODS: Twenty urology residents with no previous experience in dry-lab and robotic surgery were asked to complete four basic laparoscopic tasks (peg transfer, circle cutting, needle guidance, and suturing) laparoscopically and robotically. All participants were asked to complete the tasks first after watching the Uroweb educational material and, second, after undertaking a 2-hour training in robotic and laparoscopic dry-lab. Thereafter, all trainees continued to undertake 2-hour training programs until being able to complete the tasks with the avatera® robot at the desired time. Paired t test and one-way ANOVA test were used to analyze time differences between the groups. RESULTS: Time needed to complete all tasks either robotically or laparoscopically was significantly less in the second compared to the first attempt for all Groups in each Task. In the robotic dry-lab, time needed to complete the tasks was significantly less than in the laparoscopic dry-lab. A significant effect of previous laparoscopic experience of the participants on the training time needed to achieve most of the goal times was detected. CONCLUSION: The results of the study highlight the role of previous laparoscopic experience in the training time needed to achieve the performance time goals and demonstrate that the learning curve of basic surgical skills using the avatera® system is steeper than the laparoscopic one.

Grafts in Peyronie's surgery without the use of prostheses: a systematic review and meta-analysis.

ABSTRACT: Peyronie's disease (PD) is characterized by abnormal penile curvature, and various surgical methods have been developed using different graft materials. However, there is currently no universal agreement on which type of graft is the best. The objective of this review was to evaluate the available literature and identify the most effective graft material for penile curvature correction in PD. A literature search was conducted using electronic databases, including PubMed, Scopus, and the Cochrane Library. The patients, intervention, comparison, and outcome (PICO) approach was used to define the eligibility of studies. Two authors independently selected studies, evaluated them, and extracted data. Random-effect models using the DerSimonian-Laird method were used. Most studies were single-arm studies and had a high risk of bias. Buccal mucosa grafts (BMG) were found to result in the highest penile straightening rates and were associated with the least de novo erectile dysfunction. TachoSil grafts demonstrated a high success rate in straightening despite a higher mean preoperative curvature, while Tutoplast grafts had a higher incidence of postoperative erectile dysfunction. BMG had the highest percentage of postoperative penile straightening. Overall, the TachoSil graft showed the best performance when preoperative curvature is taken into account. Based on the available literature, BMG appear to be the most effective for penile curvature correction in PD, but this is offset by the requirement for low preoperative curvature. The TachoSil graft shows the best overall performance when preoperative curvature is considered. Comparative randomized clinical trials are still needed to determine graft superiority.

Location of ureteral access sheath in the ureter. Does it affect the fluid flow in different calyces?

Introduction: The aim of this study was to evaluate outflow variation in different locations of the pyelocaliceal system with the use of different ureteral access sheath (UAS) sizes and different UAS positioning. Material and methods: The experimental setup included an anaesthetised porcine model, a 7.5-Fr ureteroscope with a 200-µm laser fibre inserted in the working channel, a hand-held pumping irrigating system, and UAS of different sizes, namely: 9.5/11.5 Fr, 12/14 Fr, and 14/16 Fr. Each UAS was placed just below the ureteropelvic junction (UPJ) or in the mid-ureter. The ureteroscope was placed in the renal pelvis, upper and lower calyces, and outflow measurements were obtained with 3-second interval pumping for one minute in every experimental setup. Results: The UAS positioning in the mid-ureter was associated with significantly higher outflow rates in the lower calyx (p = 0.041). While the UAS was below the UPJ, we observed a trend of lower outflow rate in the lower calyx, which was completely inverted when the UAS was in the mid-ureter. Increasing the UAS size from 9.5/11.5 Fr to 12/14 Fr led to a significant increase in outflow in the renal pelvis and upper calyx (p = 0.007), but not in the lower calyx. A further increase to 14/16 Fr did not produce increased flow. Conclusions: Different locations of the pyelocaliceal system have different fluid mechanics during fURS. In the renal pelvis and upper calyx increasing the diameter of the UAS improved the outflow, whereas in the lower calyx the position of the UAS seems to be the most relevant factor. These variables should be considered when performing fURS, especially with high-power laser lithotripsy.

How Safe Are the Laparoscopic and Robotic Graspers? Evaluation of the Novel Avatera Robotic Surgical System: An Acute In Vivo Study on a Porcine Model.

OBJECTIVE: To evaluate the tissue injury caused by the force applied by the roboticassisted graspers of avatera robotic surgical system on bowel tissue. METHODS: An experimental in vivo porcine model with 1 pig was conducted. After a standard transperitoneal setup of the avatera robotic surgical system, different laparoscopic and robotic graspers were used on the bowel with maximum force applied each time. Robotic atraumatic grasper, laparoscopic right angle grasper, laparoscopic curved grasper, and laparoscopic atraumatic grasper were used. After using all graspers, the pig was sacrificed. The bowel segments were resected and sent for histological analysis. RESULTS: The pathologist reported that all the graspers caused signs of acute inflammation without any irreversible damage or signs compatible with ischemia of the tissue. No significant difference in histology was observed between the graspers. CONCLUSION: No permanent damage was caused by graspers, except for acute, reversible inflammation. Concluding, the avatera grasper could be safe to use on bowel segments, independent of the applied pressure.

The effect of percutaneous tract dilation technique on renal parenchymal trauma: An experimental in vivo study on a porcine model.

Purpose: The purpose of this study was to evaluate renal parenchymal trauma of two-step dilation compared to the conventional Amplatz gradual dilation during percutaneous nephrolithotomy on a porcine model. Materials and Methods: A nonpapillary percutaneous access tract was established under fluoroscopic guidance in both kidneys of four female pigs. On the right kidney of each pig, gradual dilation was performed using an Amplatz dilator set with a gradual dilation to 30 Fr, whereas on the left, a two-step dilation was utilized using only 16 Fr and 30 Fr dilators. Two of the animals were euthanized immediately after the procedure and the remaining two 1 month later. The pigs that were kept alive underwent a contrast-enhanced computed tomography immediately, 15, and 30 days postoperatively. A dimercaptosuccinic acid (DMSA) scintigraphy and single-photon emission computed tomography-computed tomography (CT) were also performed after the last CT and afterward, the pigs were sacrificed. All kidneys were harvested for pathohistological examination. Results: The follow-up radiologic imaging showed similar parenchymal damage caused by the compared dilation techniques and an expected reduction in scar size in the later scans. No scar was identified by DMSA in any kidney. Gross and microscopic examinations conducted both on the kidneys that were harvested immediately after the procedure and the ones from the animals that were left to heal, revealed no significant differences in tissue damage, grade of fibrosis, or inflammation depending on the dilation method. Conclusions: Our study showed no inferior outcomes caused by two-step dilation compared to gradual dilation regarding renal parenchymal damage following a nonpapillary puncture. In fact, postoperative imaging findings suggested a trend toward better healing and less scar tissue when the two-step method was used.

Non-papillary prone percutaneous nephrolithotomy for renal abnormalities: single-institution experience.

PURPOSE: To evaluate the effectiveness and safety of non-papillary prone PCNL for the treatment of patients with renal abnormalities. METHODS: An observational retrospective cohort study including PCNL cases of patients with renal abnormalities was performed. The following inclusion criteria were applied: renal stones > 1.5 cm with maximal diameter, anatomical malformations of affected kidney (malrotated kidneys, horseshoe kidneys and kidneys with complete duplicated systems, medullary sponge kidney), patients treated with standard (30Fr) PCNL or mini-PCNL (22Fr). The lithotripsy was performed using the Lithoclast Master or the Lithoclast® Trilogy (EMS Medical, Nyon, Switzerland). RESULTS: Overall, 57 patients, 35 males, and 22 females with any renal malformation underwent non-papillary prone PCNL. Our study included 25 patients with horseshoe kidneys, 21 with malrotated kidneys, 9 with kidneys with duplicated pelvicalyceal systems and 2 with medullary sponge kidneys. The mean cumulative stone size was 36 ± 1.4 mm and most of the stones were in the lower calyceal group (36.9%) and in the pelvis (27.2%). The stone-free rate (SFR) was 84.2% and the mean hospitalization time was 2.7 ± 0.7 days. In total, postoperative complications were developed in six patients (10.5%), half of them presenting fever and the other half requiring blood transfusion (Grade II). CONCLUSION: The PCNL is the method of choice for treating large stones in anomalous kidneys. The generally accepted panacea that only a papillary puncture is safe is questioned by our results. Based on our experience, a non-papillary puncture proved to be a safe and effective procedure.

The feasibility of robot-assisted radical cystectomy: an experimental study.

PURPOSE: To investigate the feasibility of the avatera system for performing robot-assisted radical cystectomy (RARC) followed by intracorporeal reconstruction of ileal neobladder. METHODS: Six anesthetized female pigs were used to perform RARC and formation of the intracorporeal orthotopic ileal neobladder. Three surgeons with different level of expertise in the use of robotic systems performed RARC after a short instructional lecture and a 2-h hands-on training. The urinary diversion phase was performed only by the experienced surgeon. The successful completion of the procedure, operative time for demolitive and reconstructive phases, intraoperative blood loss and malfunction of the robotic system were evaluated. RESULTS: An improvement of the operative time was observed for each surgeon. The experienced surgeon, the fellow and the resident improved their time by 11, 15, and 22 min, respectively, between the first and the second RARC performed. The most significant time difference was demonstrated by the resident, who had no previous experience in using robotic systems. The time difference between the first and the last orthotopic ileal neobladder creation for the experienced surgeon was 51 min. CONCLUSION: The feasibility of avatera system for performing complex surgical procedure such as RARC with intracorporeal neobladder formation was demonstrated by this experimental study. No major bleeding or severe malfunctions were observed during the procedures. Significant improvement in operative time was demonstrated with the increasing experience from 1st to 6th case.

Clearance of Metal Particles After Percutaneous Nephrolithotomy with Trilogy Lithotripter.

Purpose: To evaluate the clearance of metal particles produced and released in the pelvicaliceal system (PCS) during percutaneous nephrolithotomy (PCNL) with the use of the Swiss Lithoclast® Trilogy dual-energy (EMS Urology, Nyon, Switzerland) lithotripter. Methods: An experimental in vivo study and a clinical investigation of case series were conducted. An in vivo porcine model with two pigs for lithotripsy (after inserting artificial stones into the collecting system) and two pigs for submucosal injection of metal particles (provided by the manufacturer of Trilogy) was conducted. Porcine kidney histology analysis for metal leftovers was conducted immediately or 2 weeks after the surgery. A prospective observational study design included 10 consecutive patients treated with conventional 30F PCNL or with 22F mini-PCNL technique. Only the patients with the confirmed metal particles in the PCS during the initial PCNL and the need for additional retrograde intrarenal surgery over a period of 2-4 weeks were selected. The presence of metal particles was evaluated during the second endoscopic surgery. Results: The generated metal particles during PCNL and the submucosally injected particles were not found macroscopically 2 weeks postoperatively in porcine models. No pathologic changes such as foreign body granuloma or inflammation were found. Similarly, no metal particles were observed during the second look endoscopy (n = 10). Conclusion: Metal particles observed endoscopically using the Trilogy lithotripter are cleared with no pathologic evidence of tissue damage from the metal particles 2 weeks after the procedure. Thus, the intraoperative release of any particle by the Trilogy lithotripter should not raise any safety concerns.

Non-Papillary Access for the Percutaneous Antegrade Treatment of Renal and Ureteral Stones.

OBJECTIVE: To evaluate the feasibility and success of medial non-papillary percutaneous access for the antegrade treatment of different locations of ureteral stones, with and without concomitant renal stones. METHODS: We performed an analysis of prospectively collected data of 72 patients, being subjected to percutaneous antegrade ureterolithotripsy. Stones located anywhere in the ureter with or without concomitant renal stones were included. A 12Fr, 22Fr, or 30Fr percutaneous tract dilation was performed based on the size of the stone pelvicalyceal system. Perioperative and demographic parameters were gathered and evaluated. The Lithoclast Trilogy (EMS Medical, Nyon, Switzerland) High-power holmium laser devices Cyber Ho 150 (Quanta System, Samarate, Italy) or MOSES Pulse 120H (Lumenis Ltd, Yokneam, Israel) were used for lithotripsy. RESULTS: The average age and cumulative stone size of the patients were 57.9 ± 27.1 years and 24.2 ± 5.4 mm, respectively. The mean manipulation time was 36.9 ± 14.8 minutes. The mean hospitalization time was 2.5 ± 0.5 days and the average hemoglobin loss was 1.02 ± 0.18 gr/dL. The stone-free rate after percutaneous antegrade ureterolithotripsy was 95.8 % (69 patients), while the overall complications rate was 5.6 %, with 3 cases of fever and one case of prolonged hematuria that were treated conservatively. CONCLUSION: Non-papillary percutaneous antegrade ureterolithotripsy is a safe and reliable technique for the treatment of patients with ureteral stones, with or without the co-existence of renal stones. A high stone-free rate of 95.8% was reported at 1-month after the surgery carrying a weighted risk of developing postoperative complications.

Nonpapillary prone endoscopic combined intrarenal surgery: effectiveness, safety and tips, and tricks.

PURPOSE: To evaluate the effectiveness and safety of nonpapillary prone endoscopic combined intrarenal surgery (ECIRS) and provide practical tips and tricks for the successful accomplishment of the procedure respecting the anatomical particularities. MATERIAL AND METHODS: This study is an analysis of a prospectively collected database including all cases of ECIRS performed between January 2019 and December 2021 in a high-volume tertiary center. All patients underwent the procedure in prone-split leg position. A nonpapillary renal puncture was performed. The used access sheaths were 22Fr or 30Fr. Lithotripsy was performed anterogradely with a dual-energy lithotripter with incorporated suction and retrogradely with holmium Yttrium-Aluminum-Garnet laser. RESULTS: A total of 33 patients were included. The initial stone-free rate (SFR) was 84.8% and the final SFR was 90.9%. The median stone size was 35 mm and 60% of patients had staghorn calculi. The prevalence of renal abnormalities was 21.3%, including 3 cases of horseshoe kidney, 2 cases of malrotation and 2 cases with complete duplicated systems. The median operative time was 47 min. The median hospital stay was 3 days and median hemoglobin loss was 1.2 gr/dL. Overall, the complication rate was 9.1%, all being Grade II complications (n = 2 fever and n = 1 transient bleeding). CONCLUSIONS: Nonpapillary prone ECIRS is an effective and safe procedure. Standardization of the procedure is critical to achieve good outcomes. Patients who benefit the most are probably the ones where additional punctures can be avoided using this technique, namely patients with renal abnormalities, incrusted ureteral stents and staghorn stones.

Factors Affecting the Irrigation Fluid Temperature During Laser Lithotripsy: In Vitro Experimental Study.

OBJECTIVE: To investigate the effect of the diameter of laser fiber, pelvis volume, presence and type of the stone on irrigation fluid temperature rise. MATERIAL AND METHODS: A 20ml syringe, 12/14 ureteral access sheath(UAS), a dual-lumen catheter and a thermocouple were used.  The 12/14Fr UAS(Cook Ireland Ltd., Limerick, Ireland) and the Thermocouple(SE001, Pico Technologies, Cambridgeshire, UK) were inserted in the syringe. The syringe was closed allowing outflow from the UAS with rate at 10ml/min. The Quanta Ho 150W(Quanta System, Samarate, Italy) laser was used and fired with 10W(2Jx5Hz), 20W(2 × 10 Hz), 40W(2 × 20 Hz), 60W(2 × 30 Hz). These power settings were tested in different conditions: fibers(200µm, 365µm and 550µm), volumes(5ml, 10ml and 20ml) and artificial stones(soft, hard). The laser was activated for 30 seconds and reactivation was performed when the temperature reached below 26 °C. RESULTS: For all trials 60W of energy resulted in higher temperature rise. No differences were observed when different fibers were used. The highest temperatures (up to 80 °C) for 60W were reported in 5ml syringe and the lowest (<45 °C) with 20ml.  The maximal temperature of >59°C was recorded for the power of 60W(1Jx60Hz). The temperature exceeded 43 °C when power settings >40W were applied. CONCLUSION: Increasing the overall power, increases the irrigation fluid temperature significantly. The smaller the volume of the pelvis, the greater the temperature elevation. The fiber size did not affect the temperature increase pattern. The presence of artificial stones was associated with the absorption of energy emitted by the laser.

The effect of prolonged laser activation on irrigation fluid temperature: an in vitro experimental study.

PURPOSE: To investigate the effect of prolonged laser activation on irrigation fluid temperature by varying the power settings flow rate (10-30 ml/min). MATERIALS AND METHODS: An experimental study using a 20 ml syringe, 12/14 ureteral access sheath, a dual-lumen catheter and a thermocouple was performed. The laser was fired with 12 W (0.3 J × 40 Hz), 40 W (1 J × 40 Hz), 60 W (1.5 J × 40 Hz) using Quanta Ho 150 W (Quanta System, Samarate, Italy). All trials were performed with fluid outflow rate of 10, 20 and 30 ml/min with the fixed fluid volume at 10 ml. RESULTS: Continuous laser activation for 10 min with the outflow rate of 10 ml/min using only 12 W resulted to continuous temperature rise to as high as 83 °C. Similar rise of temperatures were observed for 40 W and 60 W with 10 ml/min outflow rate with intermittent laser activation. With 20 and 30 ml/min outflow rates the maximum temperatures for all power settings were below the threshold (< 43 °C). However, the time to reach the same total emitted energy was 60% and 40% shorter 60 W and 40 W, respectively. CONCLUSION: Our study found that continuous laser activation with as less as 12 W using 10 ml/min outflow rate increased the irrigation fluid temperature above the threshold only after 1 min. In the current experimental setup, with the fluid outflow rate of 20 and 30 ml/min safe laser activation with 60 W and 40 W (temperature < 43 °C) can be achieved reaching the same total emitted energy as with 12 W in significantly shorter time period.

Stone ablation rates using innovative pulse modulation technology: Vapor tunnel, virtual basket, and bubble blast. An in vitro experimental study.

INTRODUCTION AND OBJECTIVES: Virtual BasketTM , Bubble BlastTM , and Vapor TunnelTM are three laser pulse modulation technologies that modify the holmium: yttrium-aluminum-garnet (Ho:YAG) laser pulse transmission through the creation of bubbles emerging from the fiber tip with different effects on the target stone. The primary outcome of the current study was to test the stone ablation rates for the different pulse modulation modes, Virtual Basket, Bubble Blast, and Vapor Tunnel, using different power, energy, and frequency settings. MATERIALS AND METHODS: Quanta Cyber: Ho 150 WTM , a 365 µm PrecisionTM fiber, and hard and soft phantom BegoStonesTM were used in an in vitro experimental configuration in a saline bath. In the Virtual Basket mode, the combinations of power, energy and frequency were tested; 10 W = 0.5 J × 20 Hz, 10 W = 0.5 J × 20 Hz, 60 W = 1 J × 60 Hz and 60 W = 2 J × 30 Hz. In the Bubble Blast mode, the combinations, 12 W = 1.2J × 10 Hz, 60 W = 1.2J × 50 Hz and 60 W = 2 J × 30 Hz, were tested. Similarly, the combination of 10 W = 0.5 J × 20 Hz was tested with Vapor Tunnel mode. High-speed camera captures of the bubble formation and regular photographs of the fragmentation pattern were also taken for each mode. RESULTS: High power lithotripsy was faster and related to higher ablation rates. The Virtual Basket, Bubble Blast, and Vapor Tunnel modalities showed different ablation rates for the same energy and frequency settings. For hard stones, there was an improvement in the ablation rate using 60 W = 2 J × 30 Hz compared with 60 W = 1 J × 60 Hz and 60 W = 1.2 J × 50 Hz. The highest ablation rates were recorded using the Virtual Basket mode with the high-power settings of 2 J of energy and 30 Hz of frequency. CONCLUSIONS: The Virtual BasketTM pulse-modulation technology was related to the highest ablation rates for both hard and soft stones, compared to the Bubble BlastTM and the Vapor TunnelTM technologies in high-power and low-power lithotripsy respectively. For the same high power settings, higher energy seems to provide higher ablation rates.

Assessment of Diagnostic Yield of Cystoscopy and Computed Tomographic Urography for Urinary Tract Cancers in Patients Evaluated for Microhematuria: A Systematic Review and Meta-analysis.

Importance: Microhematuria (MH) is a common finding that often leads to further evaluation for urinary tract cancers. There is ongoing debate about the extent to which patients with MH should be evaluated for cancer. Objective: To assess the diagnostic yield for detection of urinary tract cancers, specifically bladder cancer, upper tract urothelial carcinoma (UTUC), and kidney cell carcinoma, among patients evaluated for MH using cystoscopy and computed tomographic (CT) urography. Data Sources: MEDLINE, Scopus, and Embase were systematically searched for eligible studies published between January 1, 2009, and December 31, 2019. Study Selection: Original prospective and retrospective studies reporting the prevalence of cancer among patients evaluated for MH were eligible. Two authors independently screened the titles and abstracts to select studies that met the eligibility criteria and reached consensus about which studies to include. Among 5802 records identified, 5802 articles were screened using titles and abstracts. After exclusions, 55 full-text articles were assessed for eligibility, with 39 studies selected for systematic review. Data Extraction and Synthesis: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Studies were quantitatively synthesized using a random-intercept logistic regression model. Main Outcomes and Measures: The primary outcome was diagnostic yield, defined as the proportion of patients with a diagnosis of urinary tract cancer (bladder cancer, UTUC, or kidney cell carcinoma) after presentation with MH. Studies were stratified by the percentage of cystoscopy and CT urography use and by high-risk cohorts. The diagnostic yields of CT urography and cystoscopy were calculated for each cancer type. Results: A total of 30 studies comprising 24 366 patients evaluated for MH were included in the meta-analysis. The pooled diagnostic yield among all patients was 2.00% (95% CI, 1.30%-3.09%) for bladder cancer, 0.02% (95% CI, 0.0%-0.15%) for UTUC, and 0.18% (95% CI, 0.09%-0.36%) for kidney cell carcinoma. Stratification of studies that used cystoscopy and/or CT urography for 95% or more of the cohort produced diagnostic yields of 2.74% (95% CI, 1.81%-4.12%) for bladder cancer, 0.09% (95% CI, 0.01%-0.75%) for UTUC, and 0.10% (95% CI, 0.04%-0.23%) for kidney cell carcinoma. In high-risk cohorts, the diagnostic yields increased to 4.61% (95% CI, 2.34%-8.90%) for bladder cancer and 0.45% (95% CI, 0.22%-0.95%) for UTUC. Conclusions and Relevance: This study's findings suggest that, given the low diagnostic yield of CT urography and the associated risks and costs, limiting its use to high-risk patients older than 50 years is warranted. Risk stratification, as recommended by the recent American Urology Association guidelines on MH, may be a better approach to tailor further evaluation.

Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition.

Recently, we showed that deficiency in apolipoprotein A-I (ApoA-I) sensitizes mice to diet-induced obesity, glucose intolerance and NAFLD. Here we investigated the potential involvement of ApoA-I in the pharmacological effects of metformin on glucose intolerance and NAFLD development. Groups of apoa1-deficient (apoa1(-/-)) and C57BL/6 mice fed western-type diet were either treated with a daily dose of 300 mg/kg metformin for 18 weeks or left untreated for the same period. Then, histological and biochemical analyses were performed. Metformin treatment led to a comparable reduction in plasma insulin levels in both C57BL/6 and apoa1(-/-) mice following intraperitoneal glucose tolerance test. However, only metformin-treated C57BL/6 mice maintained sufficient peripheral insulin sensitivity to effectively clear glucose following the challenge, as indicated by a [(3)H]-2-deoxy-D-glucose uptake assay in isolated soleus muscle. Similarly, deficiency in ApoA-I ablated the effect of metformin on hepatic lipid deposition and NAFLD development. Gene expression analysis indicated that the effects of ApoA-I on metformin treatment may be independent of adenosine monophosphate-activated protein kinase (AMPK) activation and de novo lipogenesis. Interestingly, metformin treatment reduced mitochondrial oxidative phosphorylation function only in apoa1(-/-) mice. Our data show that the role of ApoA-I in diabetes extends to the modulation of the pharmacological actions of metformin, a common drug for the treatment of type 2 diabetes.

The low density lipoprotein receptor modulates the effects of hypogonadism on diet-induced obesity and related metabolic perturbations.

Here, we investigated how LDL receptor deficiency (Ldlr(-/-)) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham-operated Ldlr(-/-) mice fed Western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and TG profiles, castrated mice were resistant to diet-induced obesity and had improved glucose metabolism and reduced plasma TG levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr(-/-) mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr(-/-) mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and uncoupling protein 1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr(-/-) mice for a period of 8 weeks promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham-operated Ldlr(-/-) mice with the aromatase inhibitor exemestane for 8 weeks showed that the obesity of castrated Ldlr(-/-) mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism.