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Objectives: To assess the accuracy of machine learning models in predicting kidney stone composition using variables extracted from the electronic health record (EHR). Materials and Methods: We identified kidney stone patients (n = 1296) with both stone composition and 24-hour (24H) urine testing. We trained machine learning models (XGBoost [XG] and logistic regression [LR]) to predict stone composition using 24H urine data and EHR-derived demographic and comorbidity data. Models predicted either binary (calcium vs noncalcium stone) or multiclass (calcium oxalate, uric acid, hydroxyapatite, or other) stone types. We evaluated performance using area under the receiver operating curve (ROC-AUC) and accuracy and identified predictors for each task. Results: For discriminating binary stone composition, XG outperformed LR with higher accuracy (91% vs 71%) with ROC-AUC of 0.80 for both models. Top predictors used by these models were supersaturations of uric acid and calcium phosphate, and urinary ammonium. For multiclass classification, LR outperformed XG with higher accuracy (0.64 vs 0.56) and ROC-AUC (0.79 vs 0.59), and urine pH had the highest predictive utility. Overall, 24H urine analyte data contributed more to the models' predictions of stone composition than EHR-derived variables. Conclusion: Machine learning models can predict calcium stone composition. LR outperforms XG in multiclass stone classification. Demographic and comorbidity data are predictive of stone composition; however, including 24H urine data improves performance. Further optimization of performance could lead to earlier directed medical therapy for kidney stone patients.

Introduction: Characterizing patterns of laser activation is important for assessing thermal dose during laser lithotripsy. The objective of this study was twofold: first, to quantify the range of operator duty cycle (ODC) and pedal activation time during clinical laser lithotripsy procedures, and second, to determine thermal dose in an in vitro caliceal model when 1200 J of energy was applied with different patterns of 50% ODC for 60 seconds. Methods: Data from laser logs of ureteroscopy cases performed over a 3-month period were used to calculate ODC (lasing time/lithotripsy time). Temporal and rolling 1-minute average power tracings were generated for each case. In vitro experiments were conducted using a 21 mm diameter glass bulb in a 37°C water bath, simulating a renal calix. A LithoVue ureteroscope with attached thermocouple was inserted and 8 mL/min irrigation was delivered with a 242 μm laser fiber within the working channel. In total, 1200 J of laser energy was applied in five different patterns at 20 W average power for 60 seconds. Thermal dose was calculated using the Sapareto and Dewey t(43) method. Results: A total of 63 clinical cases were included in the analysis. Mean ODC was 32% overall and 63% during the 1-minute of greatest energy delivery. Mean time of pedal activation was 3.6 seconds. In vitro studies revealed longer pedal activation times produced higher peak temperature and thermal dose. Thermal injury threshold was reached in 9 seconds when 40 W was applied at 50% ODC with laser activation patterns of 30 seconds on/off and 15 seconds on/off. Conclusion: ODC was quantified from clinical laser lithotripsy cases: 32% overall and 63% during 1-minute of peak power. Time of pedal activation is an important factor contributing to fluid heating and thermal dose. Awareness of these concepts is necessary to reduce risk of thermal injury during laser lithotripsy procedures.

Objective: The aim of this study was to describe and characterize the analgesic and opioid use for patients discharged from the emergency department (ED) with renal colic due to ureteral stone. Methods: This is a secondary analysis of a multicenter prospective trial of ED patients diagnosed by CT scan as having a symptomatic ureteral stone

Purpose: Pretreating the kidney with 100 low-energy shock waves (SWs) with a time pause before delivering a clinical dose of SWs (Dornier HM-3, 2000 SWs, 24 kV, and 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared to a protocol without pretreatment. It has been assumed that a similar reduction in injury will occur with lithotripters other than the HM-3, but experiments to confirm this assumption are lacking. In this study, we sought to verify that the lesion protection phenomenon also occurs in a lithotripter using an electromagnetic shock source and dry-head coupling. Materials and Methods: Eleven female pigs were placed in a Dornier Compact S lithotripter where the left kidney of each animal was targeted for lithotripsy treatment. Some kidneys received 2500 SWs at power level (PL) = 5 (120 SWs/min) while some kidneys were pretreated with 100 SWs at PL = 1, with a 3-minute time pause, followed immediately by 2500 SWs at PL = 5 (120 SWs/min). Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment regimen (% functional renal volume). Results: Lesion size fell by 85% (p = 0.01) in the 100 SW pretreatment group compared to the injury produced by a regimen without pretreatment. Conclusions: The results suggest that the treatment pause protection phenomenon occurs with a Dornier Compact S, a machine distinctly different from the Dornier HM-3. This result also suggests that this phenomenon may be observed generally in SW lithotripters.

Aim: Image-guided surgery (IGS) allows for accurate, real-time localization of subsurface critical structures during surgery. No prior IGS systems have described a feasible method of intraoperative reregistration after manipulation of the kidney during robotic partial nephrectomy (PN). We present a method for seamless reregistration during IGS and evaluate accuracy before and after tumor resection in two validated kidney phantoms. Materials and Methods: We performed robotic PN on two validated kidney phantoms—one with an endophytic tumor and one with an exophytic tumor—with our IGS system utilizing the da Vinci Xi robot. Intraoperatively, the kidney phantoms' surfaces were digitized with the da Vinci robotic manipulator via a touch-based method and registered to a three-dimensional segmented model created from cross-sectional CT imaging of the phantoms. Fiducial points were marked with a surgical marking pen and identified after the initial registration using the robotic manipulator. Segmented images were displayed via picture-in-picture in the surgeon console as tumor resection was performed. After resection, reregistration was performed by reidentifying the fiducial points. The accuracy of the initial registration and reregistration was compared. Results: The root mean square (RMS) averages of target registration error (TRE) were 2.53 and 4.88 mm for the endophytic and exophytic phantoms, respectively. IGS enabled resection along preplanned contours. Specifically, the RMS averages of the normal TRE over the entire resection surface were 0.75 and 2.15 mm for the endophytic and exophytic phantoms, respectively. Both tumors were resected with grossly negative margins. Point-based reregistration enabled instantaneous reregistration with minimal impact on RMS TRE compared with the initial registration (from 1.34 to 1.70 mm preresection and from 1.60 to 2.10 mm postresection). Conclusions: We present a novel and accurate registration and reregistration framework for use during IGS for PN with the da Vinci Xi surgical system. The technology is easily integrated into the surgical workflow and does not require additional hardware.

INTRODUCTION: About 1 in 11 Americans will experience a kidney stone, but underlying causes remain obscure. The objective of the present study was to separate idiopathic calcium oxalate stone formers by whether or not they showed positive evidence of forming a stone on Randall's plaque (RP). MATERIALS AND METHODS: In patients undergoing either percutaneous or ureteroscopic procedures for kidney stone removal, all stone material was extracted and analyzed using micro-CT imaging to identify those attached to RP. Twenty-four-hour urine samples were collected weeks after the stone removal procedure and patients were off of medications that would affect urine composition. The endoscopic video was analyzed for papillary pathology (RP, pitting, plugging, dilated ducts, and loss of papillary shape) by an observer blinded to the data on stone type. The percent papillary area occupied by RP and ductal plugging was quantified using image analysis software. RESULTS: Patients having even one stone on RP (N = 36) did not differ from non-RP patients (N = 37) in age, sex, BMI, or other clinical characteristics. Compared with the non-RP group, RP stone formers had more numerous, but smaller, stones, more abundant papillary RP formation, and fewer ductal plugs, both by quantitative measurement of surface area (on average, three times more plaque area, but only 41% as much plug area as in non-RP patients) and by semiquantitative visual grading. Serum and blood values did not differ between RP and non-RP stone formers by any measure. CONCLUSIONS: Growth of many small stones on plaque seems the pathogenetic scheme for the RP stone-forming phenotype, whereas the non-RP phenotype stone pathogenesis pathway is less obvious. Higher papillary plugging in non-RP patients suggests that plugs play a role in stone formation and that these patients have a greater degree of papillary damage. Underlying mechanisms that create these distinctive phenotypes are presently unknown.

OBJECTIVE: To investigate the mechanism of stone dusting in Holmium (Ho): YAG laser lithotripsy (LL). MATERIALS AND METHODS: Cylindrical BegoStone samples (6 × 6 mm, H × D) were treated in water using a clinical Ho:YAG laser lithotripter in dusting mode (0.2–0.4 J with 70–78 μs in pulse duration, 20 Hz) at various fiber tip to stone standoff distances (SD = 0, 0.5, and 1 mm). Stone damage craters were quantified by optical coherence tomography and bubble dynamics were captured by high-speed video imaging. To differentiate the contribution of cavitation vs thermal ablation to stone damage, three additional experiments were performed. First, presoaked wet stones were treated in air to assess stone damage without cavitation. Second, the laser fiber was advanced at various offset distances (OSD = 0.25, 1, 2, 3, and 10 mm) from the tip of a flexible ureteroscope to alter the dynamics of bubble collapse. Third, stones were treated with parallel fiber to minimize photothermal damage while isolating the contribution of cavitation to stone damage. RESULTS: Treatment in water resulted in 2.5- to 90-fold increase in stone damage compared with those produced in air where thermal ablation dominates. With the fiber tip placed at OSD = 0.25 mm, the collapse of the bubble was distracted away from the stone surface by the ureteroscope tip, leading to significantly reduced stone damage compared with treatment without the scope or with scope at large OSD of 3–10 mm. The average crater volume produced by parallel fiber orientation at 0.2 J after 100 pulses, where cavitation is the dominant mechanism of stone damage, was comparable with those produced by using perpendicular fiber orientation within SD = 0.25–1 mm. CONCLUSION: Cavitation plays a dominant role over photothermal ablation in stone dusting during short pulse Ho:YAG LL when 10 or more pulses are delivered to the same location.

Introduction: Encrustation of implanted urinary tract devices is associated with significant morbidity. Pellethane(®) is a polyether-based compound noted for its strength, porosity, and resistance to solvents. We assessed Pellethane thermoplastic polyurethane (TPU) with and without surface coatings 2-hydroxyethyl methacrylate (HEMA) and tetraethylene glycol dimethyl ether (TETRA) for the potential to resist encrustation in an artificial urine environment. Materials and Methods: Samples of Pellethane TPU, HEMA Pellethane TPU, TETRA Pellethane TPU, and hydrogel-coated ureteral stent (Cook(®)) were suspended in a batch-flow model with an artificial urine solution (AUS). Every 48 hours for 90 days, 40% of the solution was replaced with fresh AUS. All samples were stored in a 37°C incubator. Subsequently, the samples were thoroughly dried for 48 hours before weighing. Scanning electron microscopy was used to assess the degree of encrustation. Nu-Attom Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to determine the precise compositions of the encrustation specifically with regard to calcium, magnesium, and phosphate. Results: At the conclusion of the 90-day trial, the samples were analyzed, and the average mass changes were as follows: stent 63.78%, uncoated Pellethane TPU 11.50%, HEMA-coated Pellethane TPU 2.90%, and TETRA-coated Pellethane TPU 0.60%. Pellethane TPU products, and specifically those coated with HEMA and TETRA, exhibited less average mass increase and a lesser propensity to form encrustation than the traditional urinary tract stent. The mass increases noted on coated Pellethane devices were primarily ionic, whereas that of the stent was not. Conclusion: Pellethane, particularly with an HEMA-based preventative coating, may serve as a favorable alternative to traditional urinary stent material, providing its improved resistance to encrustation.

Background: Pandemic restrictions have changed how patients approach symptomatic kidney stones. We used a mixed-methods digital ethnographic approach to evaluate social media discussions about patient concerns and preferences for urolithiasis care during the COVID-19 pandemic. Materials and Methods: We retrospectively analyzed kidney stone-related discussions on a large social media platform using qualitative analysis and natural language processing-based sentiment analysis. Posts were mined for demographic details, treatments pursued, and health care encounters. Pre-COVID-19 (January 1, 2020-February 29, 2020) and COVID-19 (March 1, 2020-June 1, 2020) posts were extracted from the popular online Reddit discussion board, "r/KidneyStones," which is dedicated to discussions related to urolithiasis. Results: We extracted n = 649 posts (250 pre-COVID-19, 399 COVID-19); 150 from each cohort underwent thematic analysis and data extraction. Quantitative sentiment analysis was performed on 418 posts (179 pre-COVID-19, 239 COVID-19) that described stone-related decision making before intervention. Notable discussion themes during COVID-19 focused on barriers to care and concerns about stone management. Discussants exhibited more negative and anxious tones during COVID-19, based on sentiment analysis (p

Introduction: Burst wave lithotripsy is an experimental technology to noninvasively fragment kidney stones with focused bursts of ultrasound (US). This study evaluated the safety and effectiveness of specific lithotripsy parameters in a porcine model of nephrolithiasis. Methods: A 6- to 7-mm human kidney stone was surgically implanted in each kidney of three pigs. A burst wave lithotripsy US transducer with an inline US imager was coupled to the flank and the lithotripter focus was aligned with the stone. Each stone was exposed to burst wave lithotripsy at 6.5 to 7 MPa focal pressure for 30 minutes under real-time image guidance. After treatment, the kidneys were removed for gross, histologic, and MRI assessment. Stone fragments were retrieved from the kidney to determine the mass comminuted to pieces

Introduction and Objective: Urinary catheters and stents are frequently prone to catheter-associated urinary tract infections (CAUTI) through biofilm formation. Several strategies have been evaluated in search of a stent coating to reliably prevent adherence of bacteria and biofilm. Previous in vivo and in vitro research with methoxylated polyethylene glycol 3,4-dihydroxyphenylalanine (DOPA) copolymer as a candidate coating showed promising results to reduce the bacterial attachment. We aimed to further enhance this antimicrobial activity by adding antimicrobial agents to newly synthesized DOPA-based copolymers. Materials and Methods: Building on our previous experience, novel copolymers were engineered based on DOPA. Quaternary ammonium groups and silver particles were added by cross-linking to increase the antimicrobial activity through both kill-by-contact and planktonic killing. After coating polyurethane sheets and measuring contact angles, all candidate coatings were challenged in vitro with an Escherichia coli culture. The most promising coatings were then further evaluated against a panel of seven clinically relevant uropathogens and planktonic killing, and microbial attachment was determined. Results: Initially, seven coatings were developed, referred to as Surphys 093–099. The most significant increase in contact angle was identified in Surphys-095 and -098. Surphys coatings S-094, S-095, and S-098 were cross-linked with silver and exhibited profound antimicrobial properties when challenged with E. coli. Further testing demonstrated S-095 to have antimicrobial efficacy against gram-positive and gram-negative bacteria at different silver-loading concentrations. The final coating, consisting of a 2 mg/mL solution of S-095 cross-linked with 0.25 mg/mL AgNO(3), appeared to be highly bactericidal showing a ≥99.9% bacterial killing effect while remaining below cytotoxicity levels. Conclusions: We were able to engineer DOPA-based copolymers and add quaternary ammonium and silver particles, thus increasing the bactericidal properties of the coating. These coatings have exhibited a biologically significant ability to prevent uropathogens from attaching to biomaterials and represent a realistic opportunity to combat CAUTI.

Purpose: Holmium laser lithotripsy is a common modality used to fragment urinary stones during ureteroscopy. Laser energy deposited during activation produces heat and potentially causes thermal bioeffects. We aimed to characterize laser-induced heating through a computational simulation. Materials and Methods: A finite-element model was developed and used to estimate temperature in the urinary tract. Axisymmetric models of laser lithotripsy in a renal calyx, the renal pelvis, and proximal ureter were created. Heat generation by laser and heat transfer were simulated under different laser powers between 5 and 40 W. Irrigation fluid flow was introduced at rates between 0 and 40 mL/min. The model was validated by comparison with previous in vitro temperature data in a test tube, then used to calculate heating and thermal dose in the three tissue models. Results: Simulated temperature rises agreed well with most in vitro experimental measurements. In tissue models, temperature rises depended strongly on laser power and irrigation rate, and to a lesser extent on location. Injurious temperatures were reached for 5–40 W laser power without irrigation, >10 W with 5 mL/min irrigation, 40 W with 15 mL/min irrigation, and were not found at 40 mL/min irrigation. Tissue injury volumes up to 2.3 cm(3) were calculated from thermal dose. Conclusions: The results suggest a numerical model can accurately simulate the thermal profile of laser lithotripsy. Laser heating is strongly dependent on parameters and may cause a substantial temperature rise in the fluid in the urinary tract and surrounding tissue under clinically relevant conditions.

Purpose To develop a physical understanding of uretero-renoscopy irrigation, we derive mathematical models from basic physical principals, and compare these predictions with the results of bench-top experiments. Mathematical modelling can be used to understand the role of inlet pressure, tip deflection, the presence of working tools, geometric properties of the instruments used, and material properties of the irrigation fluid on resulting flow rate. Materials and Methods We develop theoretical models to describe irrigation flow in an idealised setup and compare with bench-top experiments for flow through a straight scope, a scope with a deflected tip, and a scope with a working tool inserted. The bench-top experiments were performed using Boston Scientific’s LithoVue ureteroscope and a variety of Boston Scientific working tools. Standard ureteroscope working channels have circular cross-sections, but using theoretical models we investigate whether modifications to the cross-sectional geometry can enhance flow rates. Results The theoretical flow predictions are confirmed by experimental results. Tip deflection is shown to have a negligible effect on flow rate, but the presence of working tools decreases flow significantly (for a fixed driving pressure). Flow rate is predicted to improve when tools are placed at the edge of the channel, rather than the center, and modifying the cross-sectional shape from a circle to an ellipse can further increase flow rate. Conclusions A mathematical framework is formulated and shown to accurately predict the properties of ureteroscope irrigation flow. The theoretical approach has significant potential in quantifying irrigation flow and improving ureteroscope design.

Purpose: Although cavitation during laser lithotripsy (LL) contributes to the Moses effect, the impact of cavitation on stone damage is less clear. Using different laser settings, we investigate the role of cavitation bubbles in energy delivery and stone damage. Materials and Methods: The role of cavitation in laser energy delivery was characterized by using photodetector measurements synced with high-speed imaging for laser pulses of varying durations. BegoStone samples were treated with the laser fiber oriented perpendicularly in contact with the stone in water or in air to assess the impact of cavitation on crater formation. Crater volume and geometry were quantified by using optical coherence tomography. Further, the role of cavitation in stone damage was elucidated by treatment in water with the fiber oriented parallel to the stone surface and by photoelastic imaging. Results: Longer pulse durations resulted in higher energy delivery but smaller craters. Stones treated in water resulted in greater volume, wider yet shallower craters compared with those treated in air. Stones treated with the parallel fiber showed crater formation after 15 pulses, confirmed by high-speed imaging of the bubble collapse with the resultant stress field captured by photoelastic imaging. Conclusions: Despite improved energy delivery, the longer pulse mode produced smaller crater volume, suggesting additional processes secondary to photothermal ablation are involved in stone damage. Our critical observations of the difference in stone damage treated in water vs in air, combined with the crater formation by parallel fiber, suggest that cavitation is a contributor to stone damage during LL.

Objectives: To investigate the feasibility and efficacy of live renal ultrasonography to guide Double-J ureteral stent placement at the bedside. Patients and Methods: Between April 12 and June 5, 2020, patients presenting with acute ureteral obstruction requiring decompression were prospectively selected for ultrasound-guided bedside ureteral stent placement. During stent placement, upper tract access confirmed using ultrasound with or without retrograde injection of ultrasound contrast before Double-J stent insertion. A postprocedural abdominal X-ray was obtained for stent position confirmation. Results: Eight patients (four men and four women) were offered bedside ultrasound-guided ureteral stent placement, and all eight consented to proceed. Stents were placed in seven of eight patients. One patient had an impacted ureterovesical junction stone and stricture requiring ureteroscopy and laser lithotripsy in the operating room. All patients tolerated procedures without immediate complications. Conclusion: Live renal ultrasonography can facilitate a high success rate for bedside ureteral stent placement outside the operating room. This approach is an attractive alternative to fluoroscopy-guided stent placement in the operating room and is of particular value in the COVID-19 era when judicious use of these resources is salient.

Purpose: Kidney stone recurrence rates vary between patients. A patient's risk informs the frequency and intensity of preventative interventions. Clinicians routinely use clinical experience to estimate risk. We sought to compare clinician estimated recurrence risk with the recurrence of kidney stones (ROKS) nomogram. Materials and Methods: We surveyed members of the Endourological Society with clinical expertise in kidney stones. Respondents estimated the risk of recurrence for patients in three clinical vignettes corresponding to low, intermediate, and high recurrence risk from the nomogram. Clinician estimates were compared with ROKS estimates. Results: The majority of the 318 respondents were from North America (n = 127, 40%). The most commonly estimated recurrence was 50% at 5 years. The respondents' estimates were significantly different from the ROKS predicted recurrence rate for all cases (Case 1, 50% vs 93% p

Introduction: There is evidence that patients with a history of ileostomies, who produce acidic urine and form uric acid or calcium oxalate stones, may plug some collecting ducts with calcium phosphate (CaP) and urate crystals. This is a paradoxical finding as such minerals should not form at an acid pH. One possible explanation is the presence of acidification defects due to focal damage to inner medullary collecting duct and Bellini duct (BD) cells. We sought to further investigate this hypothesis through direct measurement of ductal pH in dilated BDs in patients with ileostomies undergoing percutaneous nephrolithotomy (PCNL) for stone removal. Methods: After obtaining institutional review board approval, we used a fiber-optic pH microsensor with a 140-μm-diameter tip to measure intraluminal pH from the bladder, saline irrigant, and dilated BDs of patients undergoing PCNL. Results: Measurements were taken from three patients meeting inclusion criteria. Measured pH of bladder urine ranged from 4.97 to 5.58 and pH of saline irrigant used during surgery ranged from 5.17 to 5.75. BD measurements were achieved in 11 different BDs. Mean intraductal BD pH was more than 1 unit higher than bulk urine (6.43 ± 0.22 vs 5.31 ± 0.22, p

Introduction: Transurethral resection of bladder tumors (TURBTs) can be a challenging procedure, primarily due to limitations in tooltip dexterity, visualization, and lack of tissue depth information. A transurethral robotic system was developed to revolutionize TURBTs by addressing some of these limitations. The results of three pilot in vivo porcine studies using the novel robotic system are presented and potential improvements are proposed based on experimental observations. Materials and Methods: A transvesical endoscope with a mounted optically tracked camera was placed through the bladder of the swine under general anesthesia. Simulated bladder lesions were created by injecting HistoGel processing gel mixed with blue dye, transabdominally, into various locations in the bladder wall under endoscopic visualization. A 7-degree-of-freedom (DoF) robot was then used for transurethral resection/ablation of these simulated tumors. An independent 2-DoF distal laser arm (DLA) was deployed through the robot for laser ablation and was assisted by a manually controlled gripper for en bloc resection attempts. Results: Lesions were created and ablated using our novel endoscopic robot in the swine bladder. Full accessibility of the bladder, including the bladder neck and dome, was demonstrated without requiring bladder deflation or pubic compression. Simulated lesions were ablated using the holmium laser. En bloc resection was demonstrated using the DLA and a manual grasper. Conclusion: Feasibility of robot-assisted en bloc resection was demonstrated. Main challenges were lack of depth perception and visual occlusion induced by the transvesical endoscope. Recommendations are given to enhance robot-assisted TURBTs. Lessons learned through these pilot swine studies verify the feasibility of robot-assisted TURBTs while informing designers about critical aspects needed for future clinical deployment.

Purpose: Burst wave lithotripsy (BWL) is a new technology in development to fragment urinary stones. Ultrasonic propulsion (UP) is a separate technology under investigation for displacing stones. We measure the effect of propulsion pulses on stone fragmentation from BWL. Materials and Methods: Two artificial stone models (crystalline calcite, BegoStone plaster) and human calcium oxalate monohydrate (COM) stones measuring 5 to 8 mm were subjected to ultrasound exposures in a polyvinyl chloride tissue phantom within a water bath. Stones were exposed to BWL with and without propulsion pulses interleaved for set time intervals depending on stone type. Fragmentation was measured as a fraction of the initial stone mass fragmented to pieces smaller than 2 mm. Results: BegoStone model comminution improved from 6% to 35% (p

© Zhamshid Okhunov, et al. Introduction: We evaluated and compared five currently available energy-based vessel sealing devices to assess typical surgical metrics. Methods: We tested Caiman 5 (C5), Harmonic Scalpel Ace Plus (HA), Harmonic Ace +7 (HA7), LigaSure (LS), and Enseal G2 (ES) on small (2-5 mm), medium (5.1-7 mm), and large (7.1-9 mm) vessels obtained from 15 Yorkshire pigs. Vessels were randomly sealed and transected. We recorded sealing and transection time, charring and carbonization, thermal spread, and bursting pressure (BP). Specimens were sent for histopathologic evaluation of seal quality and thermal spread. Results: A total of 246 vessels were evaluated: 125 were arteries and 121 were veins. There was no difference in BPs for small size arteries. For medium arteries, C5 provided the highest BP (proximal and distal jaw), followed by HA7, ES, LS, and HA [1740, 1600, 1165, 1165, 981, and 571 mm Hg, respectively, HA250 mm Hg.

IntroductionEndoscopic tools have provided versatile examination and treatment for kidney stone procedures. Despite endourologists researching urinary stone disease using endoscopes to collect tissue, this tissue collection method is limited. Endoscopically removed tissues are small in size, restricting the types of genome-based examination possible. We investigated a new method of renal papilla biopsy and RNA extraction to establish a genomic research methodology for kidney stone disease.Patients and methodsWe conducted a prospective multi-institutional study and collected renal papilla specimens from consecutive percutaneous nephrolithotomy and ureteroscopy (URS) cases performed for removal of upper urinary tract stones. Renal papilla tissue was extracted using ureteroscopic biopsy forceps after stone removal. RNA was extracted using two different extraction kits, and their quantity and quality were examined. Additionally, the impact of biopsy on surgical complications was compared between cases performed with and without biopsy by matched case-control analysis adjusted for age, gender, body mass index, bilaterality, and stone burden.ResultsA total of 90 biopsies from 49 patients were performed, and the median duration between specimen collection and RNA extraction was 61 days. Both univariate and multivariate analyses showed BIGopsy® forceps usage significantly increased the total yield (p = 0.004) and quality (p = 0.001 for A260/280, p = 0.004 for A260/A230) of extracted RNA. Extraction using the RNeasy Micro Kit® also improved A260/A230, whereas reduced RNA integrity number of extracted RNA by univariate and multivariate analyses (p = 0.002 and p

Burst wave lithotripsy (BWL) is a transcutaneous technique with potential to safely and effectively fragment renal stones. Preclinical investigations of BWL require the assessment of potential renal injury. This study evaluates the capabilities of real-time ultrasound and MRI to detect and evaluate BWL injury that was induced in porcine kidneys.Ten kidneys from five female farm pigs were treated with either a 170 or 335 kHz BWL transducer using variable treatment parameters and monitored in real-time with ultrasound. Eight kidneys were perfusion fixed and scanned with a 3-Tesla MRI scanner (T1-weighted, T2-weighted, and susceptibility-weighted imaging), followed by processing via an established histomorphometric technique for injury quantification. In addition, two kidneys were separately evaluated for histologic characterization of injury quality.Observed B-mode hyperechoes on ultrasound consistent with cavitation predicted the presence of BWL-induced renal injury with a sensitivity and specificity of 100% in comparison to the histomorphometric technique. Similarly, MRI detected renal injury with a sensitivity of 90% and specificity of 100% and was able to identify the scale of lesion volumes. The injuries purposefully generated with BWL were histologically similar to those formed by shock wave lithotripsy.BWL-induced renal injury can be detected with a high degree of sensitivity and specificity by real-time ultrasound and post-treatment ex vivo MRI. No injury occurred in this study without cavitation detected on ultrasound. Such capabilities for injury detection and lesion volume quantification on MRI can be used for preclinical testing of BWL.

To evaluate and compare the acute effect of electromagnetic and electrohydraulic extracorporeal shockwave lithotripsy (SWL) on the urothelial layers of kidney and ureter.Fifty patients, 29 males (58%) and 21 females (42%), with an average age of 51.68 years (range: 37-70) who underwent SWL application in two different centers were included. Twenty-eight patients (56%) were treated with electrohydraulic and 22 (44%) were treated with electromagnetic lithotripsy. Urinary cytologic examinations were done immediately before and after SWL therapy and 10 days later. The average numbers of epithelial cells, red blood cells (RBC), and myocytes were counted under 40 × magnification.There were significant differences in the number of epithelial cells and RBC before and after immediate application of SWL: 1.66 and 14.9 cells/field, (p = 0.001), 5.44 and 113.45 cells/field, respectively (p = 0.001). The number of RBC was significantly higher in patients treated with electromagnetic lithotripsy than those treated with electrohydraulic: 141.9 and 93.4 cells/field, respectively (p = 0.02). No myocyte or basement membrane elements were detected in any of the cytologic examinations. Cytologic examinations done after 10 days of SWL therapy revealed recovery of all abnormal cytologic findings.The acute increments in the number of epithelial cells and RBC after SWL were statistically significant but it was not permanent. SWL-induced urinary urothelial lesion is limited to the mucosal layer and there was no evidence of damage to the basal membrane or muscle layer. Electromagnetic lithotripsy caused high numbers of RBC than the electrohydraulic device on the postimmediate urine cytologic examination.

Introduction: Nonmuscle-invasive bladder cancer has a relatively high postoperative recurrence rate despite the implementation of conventional treatment methods. Cystoscopy is essential for diagnosing and monitoring bladder cancer, but lesions are overlooked while using white-light imaging. Using cystoscopy, tumors with a small diameter; flat tumors, such as carcinoma in situ; and the extent of flat lesions associated with the elevated lesions are difficult to identify. In addition, the accuracy of diagnosis and treatment using cystoscopy varies according to the skill and experience of physicians. Therefore, to improve the quality of bladder cancer diagnosis, we aimed to support the cystoscopic diagnosis of bladder cancer using artificial intelligence (AI). Materials and Methods: A total of 2102 cystoscopic images, consisting of 1671 images of normal tissue and 431 images of tumor lesions, were used to create a dataset with an 8:2 ratio of training and test images. We constructed a tumor classifier based on a convolutional neural network (CNN). The performance of the trained classifier was evaluated using test data. True-positive rate and false-positive rate were plotted when the threshold was changed as the receiver operating characteristic (ROC) curve. Results: In the test data (tumor image: 87, normal image: 335), 78 images were true positive, 315 true negative, 20 false positive, and 9 false negative. The area under the ROC curve was 0.98, with a maximum Youden index of 0.837, sensitivity of 89.7%, and specificity of 94.0%. Conclusion: By objectively evaluating the cystoscopic image with CNN, it was possible to classify the image, including tumor lesions and normality. The objective evaluation of cystoscopic images using AI is expected to contribute to improvement in the accuracy of the diagnosis and treatment of bladder cancer.

Background and Objective: The ideal hemostatic agent for laparoscopic partial nephrectomy (LPN) would provide complete hemostasis and sealing of the collecting system at a low cost. Chitosan (CS) is an established topical hemostatic agent, but standard sterilization techniques affect its functional and biologic properties, thereby preventing parenteral uses. This study sought to characterize the safety and efficacy of an implanted CS hemostat sterilized with either a standard technique, electron beam (e-beam) irradiation, or a novel technique, nonthermal nitrogen plasma, in a porcine LPN model. Methods: Laparoscopic partial nephrectomies were performed on six farm pigs and hemostasis achieved using only a CS hemostatic agent (Clo-Sur P.A.D.) that was e-beam (n = 3) or plasma sterilized (PS) (n = 3). Number of pads needed to achieve hemostasis, estimated blood loss, operative time, mass of kidney resection, and warm ischemia time were measured. Animals were monitored for 14 weeks and at harvest, retrograde ureteropyelography and histologic analysis were performed. Results: Complete hemostasis and collection system sealing were achieved in both groups. There was a trend toward less pads required for hemostasis (p = 0.056) and reduced blood loss (p = 0.096) with PS pads, although this did not achieve statistical significance. No complications were observed for 14 weeks and gross examination showed the implanted CS was encapsulated in a fibrous capsule. Histologic analysis revealed a healed nephrectomy site with residual CS and associated chronic inflammation, reactive fibrosis, and foreign body giant cell formation. Importantly, the adjacent renal tissue was intact and viable with no residual parenchymal inflammation or cytologic damage. Conclusion: CS pads alone provided safe and effective hemostasis in a porcine LPN model. PS may enhance hemostatic efficacy and resorption compared with e-beam.

Objective: The goal was to test whether stone composition and kidney phantom configuration affected comminution in extracorporeal shockwave lithotripsy (SWL) laboratory tests. Confinement may enhance the accumulation of dust and associated cavitation bubbles in the fluid surrounding the stone. It is known that high shockwave delivery rates in SWL are less effective because bubbles generated by one shockwave do not have sufficient time to dissolve, thereby shielding the next shockwave. Materials and Methods: Experiments were conducted with a lithotripter coupled to a water bath. The rate of comminution was measured by weighing fragments over 2 mm at 5-minute time points. First, plaster and crystal stones were broken in four phantoms: a nylon wire mesh, an open polyvinyl chloride (PVC) cup, a closed PVC cup, and an anatomical kidney model—the phantoms have decreasing fluid volumes around the stone. Second, the fluid volume in the kidney model was flushed with water at different rates (0, 7, and 86 mL/min) to remove dust. Results: The efficiency of breakage of stones decreases for the dust emitting plaster stones (percentage of breakage in 5 minutes decreased from 92% ± 2% [n = 3] in wire mesh to 19% ± 3% [n = 3] in model calix) with increasing confinement, but not for the calcite crystal stones that produced little dust (percentage of breakage changed from 87% ± 3% [n = 3] in wire mesh to 81% ± 3% [n = 3] in kidney model). Flushing the kidney phantom at the fastest rate improved comminution of smaller plaster stones by 27%. Conclusions: Phantoms restricting dispersion of dust were found to affect stone breakage in SWL and in vitro experiments should replicate kidney environments. The dust around the stone and potential cavitation may shield the stone from shockwaves and reduce efficacy of SWL. Understanding of stone composition and degree of hydronephrosis could be used to adapt patient-specific protocols.

Introduction: With increasing use of high-power laser settings for lithotripsy, the potential exists to induce thermal tissue damage. In vitro studies have demonstrated that temperature elevation sufficient to cause thermal tissue damage can occur with certain laser and irrigation settings. The objective of this pilot study was to measure caliceal fluid temperature during high-power laser lithotripsy in an in vivo porcine model. Methods: Four female pigs (30–35 kg) were placed under general anesthesia and positioned supine. Retrograde ureteroscopy with entry into upper or middle calices was performed. Thermocouples were placed into the calix by open exposure and puncture of the kidney or retrograde alongside the ureteroscope. A 242 μm laser fiber was positioned in the center of the calix and activated (0.5 J, 80 Hz, 40 W) for 60 seconds with high, medium, or no irrigation delivered in each trial. Finite element simulations of laser-induced heating in a renal calix were also performed. Results: Peak temperatures of 84.8°C, 63.9°C, and 43.6°C were recorded for no, medium, and high irrigation, respectively. Mean time to reach threshold of thermal injury (t(43) of 120 minutes) was 12.7 and 17.8 seconds for no and medium irrigation. Thermal damage thresholds were not reached in high-irrigation trials. Numerical simulations revealed similar results with peak spatial average fluid temperatures of >100°C, 58.5°C, and 37.5°C during 60 seconds of laser activation for 0.1, 15, and 40 mL/minute irrigation, respectively. Conclusions: High-power holmium laser settings (40 W) can induce potentially injurious temperatures in the porcine in vivo model, particularly with slower irrigation rates. Characterization of thermal dose across a broader range of laser parameter settings is underway to map out the thermal safety envelope.

Histotripsy is a nonthermal, noninvasive, pulsed ultrasound technology that homogenizes tissue within the targeted volume. From previous experiments, it appeared that the resultant fibrotic response from histotripsy was limited compared with the typical tissue response seen after thermoablation. The objective of this study was to characterize the inflammatory response and quantify patterns of collagen deposition 6 weeks after in vivo canine prostate histotripsy.Histotripsy was applied to the left half of eight canine prostates to produce an intraparenchymal zone of tissue homogenization. Six weeks after treatment, prostates were harvested, sectioned, and stained with hematoxylin and eosin for histologic evaluation, CD3, CD20, and Mac387 immunohistochemistry to characterize the inflammatory components, and picrosirius red staining to identify collagen.Seven of eight treated prostates exhibited only minimal residual inflammation. Visual microscopic analysis of picrosirius red slides revealed a band of dense collagen (0.5 mm wide) immediately adjacent to the cavity produced by histotripsy. This was surrounded by a second band (1 mm wide) of less dense collagen interspersed among glandular architecture. A lobar distribution of epithelial atrophy and basal cell hyperplasia reminiscent of periurethral glands and ducts was apparent surrounding the margin of the treatment cavities. Tissue loss (-31%) was apparent on the treated side of all prostates while four demonstrated a net decrease in collagen content.In vivo histotripsy of canine prostate produced a decrease in prostate volume coupled with a limited inflammatory and fibrotic response. A narrow (1.5 mm) band of fibrosis around the empty, reepithelialized treatment cavity was observed 6 weeks after treatment. In four cases, an overall reduction in collagen content was measured. Further studies are planned to correlate these histologic findings with alteration in mechanical tissue properties and to explore histotripsy strategies for treatment of benign prostatic hyperplasia that optimize tissue volume removal with minimization of fibrosis.

We established an ex vivo model to evaluate the temperature profile of the ureter during laser lithotripsy, the influence of irrigation on temperature, and thermal spread during lithotripsy with the holmium:yttrium-aluminum-garnet (Ho:YAG) laser.Two ex vivo models of Ovis aries urinary tract and human calcium oxalate calculi were used. The Open Ureteral Model was opened longitudinally to measure the thermal profile of the urothelium. On the Clinical Model, anterograde ureteroscopy was performed in an intact urinary system. Temperatures were measured on the external portion of the ureter and the urothelium during lithotripsy and intentional perforation. The lithotripsy group (n=20) was divided into irrigated (n=10) and nonirrigated (n=10), which were compared for thermal spread length and values during laser activation. The intentional perforation group (n=10) was evaluated under saline flow. The Ho:YAG laser with a 365 μm laser fiber and power at 10W was used (1J/Pulse at 10 Hz). Infrared Fluke Ti55 Thermal Imager was used for evaluation. Maximum temperature values were recorded and compared.On the Clinical Model, the external ureteral wall obtained a temperature of 37.4°C±2.5° and 49.5°C±2.3° (P=0.003) and in the Open Ureteral Model, 49.7°C and 112.4°C with and without irrigation, respectively (P0.05). The thermal spread along the external ureter wall was not statically significant with or without irrigation (P=0.065). During intentional perforation, differences in temperatures were found between groups (opened with and without irrigation): 81.8°±8.8° and 145.0°±15.0°, respectively (P0.005).There is an increase in the external ureteral temperature during laser activation, but ureteral thermal values decreased when saline flow was applied. Ureter thermal spread showed no difference between irrigated and nonirrigated subgroups. This is the first laser lithotripsy thermography study establishing the framework to evaluate the temperature profile in the future.

In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments repositioned with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments are compared between the C5-2 and a custom (SC-50) probe that produces a longer focal beam and burst duration.Effectiveness was quantified by the number of stones expelled from a calyx phantom consisting of a 30-mm deep, water-filled well in a block of tissue mimicking material. Each probe was positioned below the phantom to move stones against gravity. Single propulsion bursts of 50 ms or 3 s duration were applied to three separate targets: 10 fragments of 2 different sizes (1-2 and 2-3 mm) and a single 4 × 7 mm human stone. Safety studies consisted of porcine kidneys exposed to an extreme dose of 10-minute burst duration, including a 7-day survival study and acute studies with surgically implanted stones.Although successful in the clinical trial, the shorter focal beam and maximum 50 ms burst duration of the C5-2 probe moved stones, but did not expel any stones from the phantom's 30-mm deep calyx. The results were similar with the SC-50 probe under the same 50 ms burst duration. Longer (3 s) bursts available with the SC-50 probe expelled all stones at both 4.5 and 9.5 cm "skin-to-stone" depths with lower probe heating compared to the C5-2. No abnormal behavior, urine chemistry, serum chemistry, or histological findings were observed within the kidney or surrounding tissues for the 10 min burst duration used in the animal studies.A longer focal beam and burst duration improved expulsion of a stone and multiple stone fragments from a phantom over a broad range of clinically relevant penetration depths and did not cause kidney injury in animal studies.

Objective: To examine the effect of ureteral access sheath (UAS) on the expression of the pro-inflammatory mediators cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the ureteral wall. Material and Methods: In 22 pigs an UAS was inserted and removed after 2 minutes on one side and 2 hours on the contralateral side. Postoperatively ureters were excised in vivo, and tissue samples from the distal (2 minutes/2 hours) and proximal ureter (2 minutes/2 hours) were snap-frozen before quantitative polymerase chain reaction analysis of COX-2 and TNF-α. Five unmanipulated ureteral units from other pigs served as the control group. Results: Compared to controls COX-2 mRNA was significantly upregulated in all UAS treated ureteral groups. Similarly, TNF-α mRNA was upregulated in all groups except the 2-minute proximal ureteral group. Both COX-2 and TNF-α expression were significantly higher in the distal than in the proximal ureter in the UAS treated ureters. After UAS insertion for 2 minutes, expression levels in the distal ureter were increased 6.5- and 8-fold for COX-2 and TNF-α, respectively; and after 2 hours of UAS placement COX-2 and TNF-α mRNA expression levels were increased 9- and 9.5-fold, respectively. Conclusion: The pro-inflammatory mediators COX-2 and TNF-α were significantly upregulated in the ureteral wall by the influence of UAS. These findings may have implications for postoperative pain, drainage, and complications.

Determine the influence of passage through the body wall on the properties of lithotripter shock waves (SWs) and the characteristics of the acoustic field of an electromagnetic lithotripter.Full-thickness ex vivo segments of pig abdominal wall were secured against the acoustic window of a test tank coupled to the lithotripter. A fiber-optic probe hydrophone was used to measure SW pressures, determine shock rise time, and map the acoustic field in the focal plane.Peak positive pressure on axis was attenuated roughly proportional to tissue thickness-approximately 6% per cm. Irregularities in the tissue path affected the symmetry of SW focusing, shifting the maximum peak positive pressure laterally by as much as ∼2 mm. Within the time resolution of the hydrophone (7-15 ns), shock rise time was unchanged, measuring ∼17-21 ns with and without tissue present. Mapping of the field showed no effect of the body wall on focal width, regardless of thickness of the body wall.Passage through the body wall has minimal effect on the characteristics of lithotripter SWs. Other than reducing pulse amplitude and having the potential to affect the symmetry of the focused wave, the body wall has little influence on the acoustic field. These findings help to validate laboratory assessment of lithotripter acoustic field and suggest that the properties of SWs in the body are much the same as have been measured in vitro.

Background and Purpose: Obtaining renal access is one of the most important and complex steps in learning percutaneous nephrolithotomy (PCNL). Ideally, this skill should be practiced outside the operating room. There is a need for anatomically accurate and cheap models for simulated training. The objective was to develop a cost-effective, anatomically accurate, nonbiologic training model for simulated PCNL access under fluoroscopic guidance. Methods: Collecting systems from routine computed tomography urograms were extracted and reformatted using specialized software. These images were printed in a water-soluble plastic on a three-dimensional (3D) printer to create biomodels. These models were embedded in silicone and then the models were dissolved in water to leave a hollow collecting system within a silicone model. These PCNL models were filled with contrast medium and sealed. A layer of dense foam acted as a spacer to replicate the tissues between skin and kidney. Results: 3D printed models of human collecting systems are a useful adjunct in planning PCNL access. The PCNL access training model is relatively low cost and reproduces the anatomy of the renal collecting system faithfully. A range of models reflecting the variety and complexity of human collecting systems can be reproduced. The fluoroscopic triangulation process needed to target the calix of choice can be practiced successfully in this model. Conclusions: This silicone PCNL training model accurately replicates the anatomic architecture and orientation of the human renal collecting system. It provides a safe, clean, and effective model for training in accurate fluoroscopy-guided PCNL access.

There is a need to improve prescreening determination of prostate cancer to better select patients who need biopsy. Such a strategy properly implemented, will decrease the number of negative biopsies for prostate cancer and in turn better balance the risks and morbidity for patients recommended for biopsy. The aim of study is to investigate Doppler spectral waveform parameters of neurovascular bundle (NVB) vessels and determine differences between benign and malignant pathologies.We performed a prospective analysis involving 292 patients who received prostate biopsy for elevated prostate-specific antigen (PSA) values or abnormal digital rectal examination, as well as 174 patients with symptomatic benign prostatic hyperplasia. Doppler spectral waveform (DSW) parameters (peak-systolic velocity [PSV], end-diastolic velocity [EDV], and resistive index [RI]) were measured at bilateral NVB vessels through Doppler transrectal ultrasound at the right lateral decubitus position, compared, and analyzed among patients with benign versus malignant histology for each side.Overall, both PSV and EDV at malignant sides were significantly higher than those at benign sides, as well as lower RI (all p-values0.05, unpaired t-test). In subgroup analysis with 93 patients of serum PSA between 10 and 20 ng/mL and 56 patients with one-side malignancy, higher EDV and lower RI were significantly associated with malignancies (all p0.05). The values of PSV and EDV rather than RI might be influenced by the patients' position and RI by the prostate volume.In this study, DSW parameters (mainly EDV and RI) at NVB vessels were significantly associated with prostate cancer, particularly in patients with serum PSA of 10-20 ng/mL. It should be in caution that the patients' position and prostate volume may influence the Doppler signal as demonstrated in the current study. These findings can provide more diagnostic information before prostate biopsy.

Magnesium (Mg(2+)) has been shown to be a kidney stone inhibitor; however, the exact mechanism of its effect is unknown. Using theoretical models, the interactions of calcium and oxalate were examined in the presence of Mg(2+).Molecular dynamics simulations were performed with NAMD and CHARMM27 force field. The interaction between calcium (Ca(2+)) and oxalate (Ox(2-)) ions was examined with and without magnesium. Concentrations of calcium and oxalate were 0.1 M and 0.03 M, respectively, and placed in a cubic box of length ~115 Angstrom. Na(+) and Cl(-) ions were inserted to meet system electroneutrality. Mg(2+) was then placed into the box at physiologic concentrations and the interaction between calcium and oxalate was observed. In addition, the effect of citrate and pH were examined in regard to the effect of Mg(2+) inhibition. Each system was allowed to run until a stable crystalline structure was formed.The presence of Mg(2+) reduces the average size of the calcium oxalate and calcium phosphate aggregates. This effect is found to be Mg(2+) concentration-dependent. It is also found that Mg(2+) inhibition is synergistic with citrate and continues to be effective at acidic pH levels.The presence of magnesium ions tends to destabilize calcium oxalate ion pairs and reduce the size of their aggregates. Mg(2+) inhibitory effect is synergistic with citrate and remains effective in acidic environments. Further studies are needed to see if this can be applied to in vivo models as well as extending this to other stone inhibitors and promoters.

The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia

Benign prostatic hyperplasia is one of the most common conditions in middle-aged and elderly men. The aim of the study was to investigate the treatment effects of low-frequency ultrasound combined with a microbubbles agent on benign prostatic hyperplasia.Eighteen 7-year-old male beagles with prostatic hyperplasia were randomly divided into six groups (n=3): Control group, 21 kHz ultrasound group, 21 kHz ultrasound and microbubble contrast agent group, 1 MHz ultrasound group, 1 MHz ultrasound and microbubble contrast agent group, and microbubble contrast agent group. The histopathologic damage to prostate cells was assessed via transmission electron microscopy and optical microscopy. The protein expressions of prostate-specific antigen (PSA), inducible nitric oxide synthase (iNOS), and super oxidase dimutase (SOD) were detected by enzyme-linked immunosorbent assay. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) were detected by the Biochemistry Automatic Analyzer.Significant tissue injury, mitochondria injury, and cell apoptosis were observed in 21 kHz ultrasound and the microbubble contrast agent group. Compared with the control and microbubbles contrast agent groups, the decrease in levels of PSA or increase in levels of iNOs and SOD in the other four groups were statistically significant (P0.05). The lowest level of PSA and the highest levels of iNOs and SOD were observed in the 21 kHz ultrasound and microbubbles contrast agent group. No significant changes in levels of AST, ALT, BUN, and Cr were observed between the six groups.Our results suggest that lower frequency ultrasound may have a better effect on benign prostatic hyperplasia, and microbubble contrast agent application further strengthens this biological effect.

Background and PurposeRecent advances in distal sensor technologies have made distal sensor ureteroscopes both commercially and technically feasible. We evaluated performance characteristics and optics of a new generation distal sensor Flex-XC (XC) and a standard flexible fiberoptic ureteroscope Flex-X2 (X2), both from Karl Storz, Tuttlingen, Germany.Materials and MethodsThe ureteroscopes were compared for active deflection, irrigation flow, and optical characteristics. Each ureteroscope was evaluated with an empty working channel and with various accessories. Optical characteristics (resolution, grayscale imaging, and color representation) were measured using United States Air Force test targets. We digitally recorded a renal porcine ureteroscopy and laser ablation of a stone with the X2 and with the XC. Edited footage of the recorded procedure was shown to different expert surgeons (n=8) on a high-definition monitor for evaluation by questionnaire for image quality and performance.ResultsThe XC had a higher resolution than the X2 at 20 and 10 mm 3.17 lines/mm vs 1.41 lines/mm, 10.1 vs 3.56, respectively (P=0.003, P=0.002). Color representation was better in the XC. There was no difference in contrast quality between the two ureteroscopes. For each individual ureteroscope, the upward deflection was greater than the downward deflection both with and without accessories. When compared with the X2, the XC manifested superior deflection and flow (P

Conduct a laboratory evaluation of a novel low-pressure, broad focal zone electrohydraulic lithotripter (TRT LG-380).Mapping of the acoustic field of the LG-380, along with a Dornier HM3, a Storz Modulith SLX, and a XiXin CS2012 (XX-ES) lithotripter was performed using a fiberoptic hydrophone. A pig model was used to assess renal response to 3000 shockwaves (SW) administered by a multistep power ramping protocol at 60 SW/min, and when animals were treated at the maximum power setting at 120 SW/min. Injury to the kidney was assessed by quantitation of lesion size and routine measures of renal function.SW amplitudes for the LG-380 ranged from (P(+)/P(-)) 7/-1.8 MPa at PL-1 to 21/-4 MPa at PL-11 while focal width measured ~20 mm, wider than the HM3 (8 mm), SLX (2.6 mm), or XX-ES (18 mm). For the LG-380, there was gradual narrowing of the focal width to ~10 mm after 5000 SWs, but this had negligible effect on breakage of model stones, because stones positioned at the periphery of the focal volume (10 mm off-axis) broke nearly as well as stones at the target point. Kidney injury measured less than 0.1% FRV (functional renal volume) for pigs treated using a gradual power ramping protocol at 60 SW/min and when SWs were delivered at maximum power at 120 SW/min.The LG-380 exhibits the acoustic characteristics of a low-pressure, wide focal zone lithotripter and has the broadest focal width of any lithotripter yet reported. Although there was a gradual narrowing of focal width as the electrode aged, the efficiency of stone breakage was not affected. Because injury to the kidney was minimal when treatment followed either the recommended slow SW-rate multistep ramping protocol or when all SWs were delivered at fast SW-rate using maximum power, this appears to be a relatively safe lithotripter.

Cavitation plays a significant role in the efficacy of stone comminution during shockwave lithotripsy (SWL). Although cavitation on the surface of urinary stones helps to improve fragmentation, cavitation bubbles along the propagation path may shield or block subsequent shockwaves (SWs) and potentially induce collateral tissue damage. Previous in vitro work has shown that applying low-amplitude acoustic waves after each SW can force bubbles to consolidate and enhance SWL efficacy. In this study, the feasibility of applying acoustic bubble coalescence (ABC) in vivo was tested. Model stones were percutaneously implanted and treated with 2500 lithotripsy SWs at 120 SW/minute with or without ABC. Comparing the results of stone comminution, a significant improvement was observed in the stone fragmentation process when ABC was used. Without ABC, only 25% of the mass of the stone was fragmented to particles

To test the hypothesis that shock wave lithotripsy machines vary in their ability to fragment standardized artificial urinary calculi.An in vitro test configuration was used to fragment synthetic U-30 Gypsum (U.S. Gypsum, Chicago, IL) stones (mean length 7.1 ± 0.2 mm, mean diameter 6.5 ± 0.07 mm, mean mass 299 ± 16 mg) using the Sonolith i-sys (EDAP TMS, Vaulx-en-Velin, France), Modulith SLX F2 (Storz Medical AG, Tägerwilen, Switzerland), and Piezolith 3000 (Richard Wolf GmbH, Knittlingen, Germany) lithotripters. Gypsum stones were placed at the nominal focus and treated with 250, 500, or 1000 shocks. The residual mass following passage through a 2-mm wire mesh was measured and compared using ANOVA and the Tukey-Kramer HSD test.There was no statistically significant difference between the Modulith SLX F2 and Piezolith 3000 lithotripters for 250 and 1000 shock treatments (p = 0.34 and 0.31, respectively). The Piezolith 3000 demonstrated the most favorable stone mass reduction for 500 shock treatments (187.4 ± 45.2 mg). The Sonolith i-sys was found to be significantly less effective than the other lithotripters for all shockwave conditions. Furthermore, performance of the Sonolith i-sys decreased beyond a threshold generator electrode age of 6000 shocks.This in vitro study found considerable variability in the ability of lithotripters to fragment synthetic urinary calculi. Synthetic stones were employed to provide a repeatable means of assessing variability in fragmentation efficiency of lithotripters. The Modulith SLX F2 and Piezolith 3000 are broadly equal and resulted in greater fragmentation efficiencies than the Sonolith i-sys. The performance of the Sonolith i-sys deteriorates at 6000 shocks, before the specified lifetime of 20,000 shocks.

Partial nephrectomy (PN) can be technically challenging, especially if performed in a minimally invasive manner. Although ultrasound technology has been shown to have therapeutic capabilities, including tissue ablation and hemostasis, it has not gained clinical use in the PN setting. The purpose of this study is to evaluate the ability of a high-intensity ultrasound clamp to create an ablation plane in the kidney providing hemostasis that could potentially aid in laparoscopic PN.A new instrument was created using a laparoscopic Padron endoscopic exposing retractor. Ultrasound elements were engineered on both sides of the retractor to administer high-intensity ultrasound energy between the two sides of the clamp. This high-intensity focused ultrasound (HIFU) clamp was placed 2 to 2.5 cm from the upper and lower poles of 10 porcine kidneys to evaluate its effectiveness at different levels and duration of energy delivery. PN transection was performed through the distal portion of the clamped margin. Kidneys postintervention and after PN were evaluated and blood loss estimated by weighing gauze placed at the defect. Histologic analysis was performed with hematoxylin and eosin and nicotinamide adenine dinucleotide staining to evaluate for tissue viability and thermal spread.Gross parenchymal changes were seen with obvious demarcation between treated and untreated tissue. Increased ultrasound exposure time (10 vs 5 and 2 min), even at lower power settings, was more effective in causing destruction and necrosis of tissue. Transmural ablation was achieved in three of four renal units after 10 minutes of exposure with significantly less blood loss (2 g vs 30-100 g). Nonviable tissue was confirmed histologically. There was minimal thermal spread outside the clamped margin (1.2-3.2 mm).In this preliminary porcine evaluation, a novel HIFU clamp induced hemostasis and created an ablation plane in the kidney. This technology could serve as a useful adjunct to laparoscopic PN in the future and potentially obviate the need for renal hilar clamping.

To evaluate differences in the serum concentrations of cell adhesion molecules (CAMs) after retroperitoneal laparoscopic and conventional open radical nephrectomies for localized renal-cell carcinoma (RCC).A total of 62 patients with stage T(1)N(0)M(0) RCC were randomized to either a retroperitoneal laparoscopic radical nephrectomy group (n=31) or an open group (n=31). Serum levels of soluble cluster of differentiation 44 splice variant 6 (sCD44v6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble epithelial cadherin (sE-cadherin) were determined independently by enzyme linked immunosorbent assay (ELISA) preoperatively, and on postoperative days 1 and 5. In addition, follow-up results were compared.On postoperative day 1, sCD44v6, sICAM-1, and sVCAM-1 levels increased significantly compared with preoperative levels in both groups (P0.05). sE-cadherin levels decreased compared with preoperative levels in both groups without statistically significant differences (P0.05). sCD44v6 levels in the retro-laparoscopy group were significantly higher than in the open group (P0.05), while sICAM-1, sVCAM-1, and sE-cadherin levels showed no statistically significant differences between both groups (P0.05). On postoperative day 5, all parameters in both groups were similar to preoperative values (P0.05). Follow-up ranged from 7 to 18 months postoperatively in all 62 patients, with a 100% cancer-specific survival rate in each group.Although postoperatively higher serum concentrations of CAMs in both groups and significantly elevated sCD44v6 in the retro-laparoscopy group may be facilitated, the differences in CAMs between both groups are small and transient. Together with the similar follow-up results, this further supports previous studies that failed to show a difference in the oncologic outcomes between open and laparoscopic radical nephrectomy and provides a probable molecular mechanism.

Struvite in kidney stones is an important marker for infection. In kidney stone samples, struvite is known to be prone to chemical breakdown, but no data exist on the stability of samples stored in dry form. The objective of this study was to examine stability of struvite under increasingly poor conditions of storage.Samples of struvite kidney stones were broken to obtain 38 pieces averaging 67 mg in weight, and these were randomized into four storage conditions: Airtight containers stored in the dark, open containers in the dark, open containers in ambient light, and open containers at elevated temperature (40°C). Pieces were left for 6 months, and then analyzed for changes using micro CT and Fourier transform infrared spectroscopy (FT-IR).Initial samples proved to be struvite, indicating no transformation in the large specimens that had been stored in airtight containers in the dark for more than 6 years before this study. Pieces of struvite taken from these large specimens appeared unchanged by micro CT and FT-IR after being stored in closed containers for 6 months, but 8 of 9 pieces in open containers showed the presence of newberyite in surface layers, as did 10 of 10 pieces in open containers out in ambient light. All pieces stored at 40°C showed transformation of struvite, with 60% of the pieces showing the presence of amorphous phosphates, indicating complete breakdown of struvite in the surface layers of the pieces.We conclude that struvite in dry kidney stone samples is stable when the specimens are stored in airtight containers at room temperature, even after several years.

Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration.Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1-3/prostate ≥1 cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE.Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively.Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking.

Oxalobacter formigenes (OF) may play a protective role in preventing calcium oxalate stones. This is the first prospective study to evaluate the effect of antibiotics on OF colonization. Intestinal colonization by OF is associated with reduced urinary oxalate excretion. Exposure to antibiotics may be an important factor determining rates of colonization.The effect of antibiotics on OF colonization was compared in two groups: A group receiving antibiotics for gastric infection with Helicobacter pylori (HP) and a group without HP whose members were not receiving antibiotics. OF colonization in stool was detected by oxalate degradation at baseline and after 1 and 6 months.The prevalence at baseline of intestinal colonization with OF was 43.1% among all patients screened. Among the 12 patients who were positive for OF who did not receive antibiotics, 11 (92%) had OF on stool tests at 1 month and 6 months. Of the 19 participants who were positive for OF and who received antibiotics for HP, only 7 (36.8%) continued to be colonized by OF on follow-up stool testing at 1 and 6 months (P=0.003 by Fisher exact test). Amoxicillin and clarithromycin caused 62.5% of subjects to become negative for OF at 1 month; 56.2% remained negative for OF at 6 months.Antibiotics for HP infection effectively reduced colonization with OF, an effect present at 1 and 6 months after treatment. The lasting elimination of OF could be associated with hyperoxaluria and be a factor in recurrent kidney stone disease.

Histotripsy is a noninvasive, pulsed ultrasound technology that produces mechanically homogenized tissue within targeted volumes. Previous work has demonstrated prostatic tissue debulking in a canine model. The aim was to establish safety thresholds by evaluating histologic changes of urinary sphincter, neurovascular bundle (NVB), and rectum after targeted histotripsy treatment of these critical structures.Rectum, urinary sphincter, and NVB in five anesthetized canines were targeted for histotripsy treatment (50 total points). Locations received 1k, 10k, or 100k acoustic pulses (4 microsecond, 1 MHz) at a repetition frequency of 500 Hz. Canine subjects were euthanized immediately (2), survived 3 days (1), or 2 weeks (3) after treatment. Prostates, periprostatic tissue, and rectum were harvested and processed for histology.The sphincter was structurally intact with minimal muscle fiber disruption even after 100k pulses (n=10). Undamaged nerves, arteries, and veins of the NVB were seen despite mechanical homogenization of surrounding loose connective tissue (n=19). The rectum, however, exhibited dose-dependent damage (n=20). 1k pulses yielded mild submucosal hemorrhage. 10k pulses resulted in moderate collagen disruption and focal mucosal homogenization. 100k pulses produced damage to the mucosa and muscularis propria with extensive hemorrhage and collagen disruption. One canine treated with 100k pulses needed early euthanasia (day 3) because of complications from a urine leak.Histotripsy histologic tissue effect varied based on targeted structure with substantial structural preservation of NVB and sphincter. Rectal subclinical damage was apparent after 1k pulses and increased in extent and severity with escalating doses. Future work will include assessment of functional outcomes and refinement of these initial safety thresholds.

Histotripsy is a pulsed focused ultrasound technology in which initiation and control of acoustic cavitation allow for precise mechanical fractionation of tissues. The present study examines the feasibility of using histotripsy for erosion of urinary calculi.Histotripsy treatment was delivered from a 750-kHz transducer in the form of 5-cycle acoustic pulses at a 1-kHz pulse repetition frequency. Model stones were sonicated for 5 minutes at peak negative pressures (p-) of 10, 15, 19, 22, and 24-MPa. Resulting fragment sizes and comminution rates were assessed and compared with those achieved with a piezoelectric lithotripter (Wolf Piezolith 3000) operated at 2-Hz pulse repetition frequency and power level 17 (p- = 14-MPa).Histotripsy eroded the surface of stones producing fine (100 μm) particulate debris in contrast to the progressive and incomplete subdivision of stones achieved with piezoelectric lithotripsy. The histotripsy erosion rate increased with increasing peak negative pressure from 10 to 19 MPa and then saturated, yielding an average rate of 87.9 ± 12.8 mg/min at maximum treatment intensity. Piezoelectric lithotripsy achieved an average treatment rate of 110.7 ± 27.4 mg/min.Histotripsy comminution of urinary calculi is a surface erosion phenomenon that is mechanistically distinct from conventional shockwave lithotripsy (SWL), producing only fine debris as opposed to coarse fragments. These characteristics suggest that histotripsy offers a potential adjunct to traditional SWL procedures, and synergistic interplay of the two modalities may lead to possible increases in both rate and degree of stone fragmentation.

Microporous polysaccharide hemospheres (MPH) are hemostatic beads engineered from purified plant starch. MPH accelerates the natural clotting cascade by concentrating clotting factors and proteins on their surface while absorbing aqueous and low molecular weight components from blood. The purpose of this study was to determine the efficacy of MPH in achieving hemostasis in the setting of laparoscopic renal injury.In four domestic pigs, 16 laparoscopic renal trocar injuries were created (8 each of 12 and 5 mm). A standard hand-assisted laparoscopic approach was used to each kidney so that two lesions per kidney were randomly created. MPH was applied to each treatment lesion with light pressure maintained for 60 seconds. Four of the 16 lesions, two each of 12 and 5 mm, were allowed to bleed as controls. Hemostasis was defined as no active bleeding or oozing. The animals were sacrificed at the conclusion of the procedure.The mean time to hemostasis for the 12-mm MPH and control lesions was 196.2 +/- 53.3 and 372.0 +/- 225.6 seconds, while the average blood loss was 8.3 +/- 3.7 and 12.0 +/- 4.9 g, respectively. For the 5-mm MPH and control lesions, the average time to hemostasis was 100.2 +/- 24.8 and 247.0 +/- 134.4 seconds, while the average blood loss was 8.3 +/- 3.8 and 9.0 +/- 0.7 g, respectively. The median number of applications of the MPH for the 5- and 12-mm injuries was 1 and 2, respectively.MPH provided a rapid and effective means of hemostasis for laparoscopic renal parenchymal injuries in this model. Additional evaluation is warranted, however, before general application is advisable.