Kathleen Kieran

Histotripsy: Minimally Invasive Technology for Prostatic Tissue Ablation in an In Vivo Canine Model

OBJECTIVES Symptoms of benign prostatic hyperplasia affect men increasingly as they age. Minimally invasive therapies for the treatment of benign prostatic hyperplasia continue to evolve. We describe histotripsy, a noninvasive, nonthermal, focused ultrasound technology for precise tissue ablation, and report the initial results of using histotripsy for prostatic tissue ablation in an in vivo canine model. METHODS An annular 18-element, 750-kHz, phased-array ultrasound system delivered high-intensity (22 kW/cm(2)), ultrasound pulses (15 cycles in 20 ms) at pulse repetition frequencies of 100 to 500 Hz to canine prostates. Eight lateral lobe and nine periurethral treatments were performed in 11 anesthetized dogs. Diagnostic ultrasound transducers provided in-line and transrectal imaging. Retrograde urethrography was performed before and after the periurethral treatments. After treatment, the prostates were grossly examined, sectioned, and submitted for histologic examination. RESULTS In the lateral lobe treatments, a well-demarcated cavity containing liquefied material was present at the ablation site. Microscopically, the targeted volume was characterized by the presence of histotripsy paste (debris, absent cellular structures). A narrow margin of cellular injury was noted, beyond which no tissue damage was apparent. The periurethral treatments resulted in total urethral ablation or significant urethral wall damage, with visible prostatic urethral defects on retrograde urethrography. Real-time ultrasound imaging demonstrated a dynamic hyperechoic zone at the focus, indicative of cavitation and suggesting effective tissue ablation. CONCLUSIONS The results of our study have shown that histotripsy is capable of precise prostatic tissue destruction and results in subcellular fractionation of prostate parenchyma. Histotripsy can also produce prostatic urethral damage and thereby facilitate drainage of finely fractionated material per urethra, producing immediate debulking.

Hospital characteristics and use of innovative surgical therapies among patients with kidney cancer.

Background:Despite their potential benefits to patients, the adoption of partial nephrectomy and laparoscopic kidney cancer surgery has been both gradual and concentrated in select hospitals. Objective:We assessed the degree to which adjusting for hospital structural characteristics modifies the association between hospital nephrectomy volume and patient receipt of partial nephrectomy and/or laparoscopic kidney cancer surgery. Research Design and Subjects:From the Nationwide Inpatient Sample, we identified an unweighted sample of 4943 patients who underwent kidney cancer surgery in 2003. Main Outcome Measure:Our primary outcomes were patient receipt of (1) partial nephrectomy and/or (2) laparoscopic kidney cancer surgery. Results:Our weighted analytic cohort comprised 34,045 cases. Overall, 16% of patients received a partial nephrectomy, and 17% underwent laparoscopic surgery; at high-nephrectomy-volume hospitals the proportions increased to 22% and 26%, respectively. Hospital structural characteristics varied across nephrectomy-case volume strata. In unadjusted models, patients treated at hospitals in the highest-nephrectomy-volume tercile were more likely than those treated at low-volume facilities to receive a partial nephrectomy [Risk RatioPN (RRPN) 2.2; 95% confidence interval (CI), 1.6–2.8] or laparoscopic surgery (RRlap 2.9; 95% CI, 2.0–4.0). Adjusting for differences in hospital structure attenuated the association between hospital nephrectomy volume and use of partial nephrectomy or laparoscopy by 60% (adjusted RRPN 1.4; 95% CI, 0.9–2.2) and 12% (adjusted RRlap 2.5; 95% CI, 1.4–4.1), respectively. Conclusions:Changes to the hospital environment may facilitate greater use of partial nephrectomy at hospitals that infrequently perform kidney cancer surgery. Efforts to increase the uptake of laparoscopy are probably best directed at surgeon-specific adoption barriers.

Histotripsy for the treatment of BPH: evaluation in a chronic canine model

Histotripsy was evaluated as a non-invasive BPH treatment. The prostates of 20 canine subjects were targeted with one of three histotripsy doses. Prostates were harvested immediately, 7 days, or 28 days after treatment and assessed for changes. Lower treatment doses were found to produced scattered cellular disruption and hemorrhage that was sometimes reversible. Higher doses perforated the urethra and produced cavities in the glandular prostate that healed to leave an enlarged urinary channel.

Exploring the Acoustic Parameter Space in Ultrasound Therapy: Defining the Threshold for Cavitational Effects

Focused ultrasound energy is capable of noninvasively, nonthermally ablating tissue. However, the relative contributions of thermal and cavitational effects in the therapeutic use of ultrasound are poorly understood. We sought to identify the ultrasound parameter space within which tissue can be ablated by solely mechanical means (cavitation), without a significant thermal component. Methods: Ultrasound energy (750 kHz, 20 microsecond pulses) was applied sequentially in a 3×3 grid configuration to the cortical tissue of ex vivo porcine kidneys submerged in degassed water. While maintaining constant energy density, intensity (0.11–211 kW/cm2) and duty cycle (0.04%‐CW) were varied widely. A thermocouple co‐localized with the center of each grid provided continuous temperature measurements. Following ablations, the kidneys were examined grossly and histologically. Results: Ablated tissue was classified into one of four discrete morphologic categories: blanched (firm, pale, desiccated tissue), disrupted (cavity containing thin, isochromatic liquid; no blanching), mixed blanched/disrupted (cavity containing pale, thick liquid; minimal blanching), and no grossly visible effect. Morphologically similar lesions clustered together within the ultrasound parameter space. Disrupted lesions had significantly lower maximal temperatures (44.2 °C) than desiccated (67.5 °C; p<0.0001) or mixed (59.4 °C; p<0.0001) lesions. Conclusions: In an ex vivo model, we have defined the ultrasound parameters within which mechanical tissue ablation, with minimal thermal components, is possible. Future research in vivo is directed toward optimizing the parameters for cavitational tissue ablation, and better understanding the impact of tissue perfusion on lesion generation and intralesional temperature rise.Focused ultrasound energy is capable of noninvasively, nonthermally ablating tissue. However, the relative contributions of thermal and cavitational effects in the therapeutic use of ultrasound are poorly understood. We sought to identify the ultrasound parameter space within which tissue can be ablated by solely mechanical means (cavitation), without a significant thermal component. Methods: Ultrasound energy (750 kHz, 20 microsecond pulses) was applied sequentially in a 3×3 grid configuration to the cortical tissue of ex vivo porcine kidneys submerged in degassed water. While maintaining constant energy density, intensity (0.11–211 kW/cm2) and duty cycle (0.04%‐CW) were varied widely. A thermocouple co‐localized with the center of each grid provided continuous temperature measurements. Following ablations, the kidneys were examined grossly and histologically. Results: Ablated tissue was classified into one of four discrete morphologic categories: blanched (firm, pale, desiccated tissue), disrupted (cavi...

Laparoscopic donor nephrectomy: An update

Laparoscopic donor nephrectomy was developed primarily to increase the number of kidneys available for donation. Further evidence of the safety and efficacy of laparoscopic donor nephrectomy has been reported in the literature, as have studies on the cost-effectiveness of this procedure and its role in removing disincentives for renal donation. Specific technical modifications have been developed and refined that improve outcomes when performing laparoscopic harvesting of right kidneys. Other technical modifications have been developed for use in obese patients. With the adoption of these modified techniques, equivalent results to open donor nephrectomy have been reported. Recently, a wide range of alternative approaches (hand-assisted, retroperitoneal, and gasless laparoscopy) have been utilized for laparoscopic donor nephrectomy.

Author's Response to Letter to the Editor

We would like to extend our gratitude to the authors for their constructive comments on our study with regard to highlighting the factors affecting the outcomes of percutaneous nephrolithotomy (PNL) in horseshoe kidneys. So far, investigators have proposed scoring systems that use the findings of computed tomography to predict the outcome of PNL for kidney stones. Stone size, number of calices involved, tract length, stone density, grade of hydronephrosis, and body mass index have been specified as important factors affecting the success of these procedures. The Guy’s stone score and STONE nephrolithometry have been validated as predictors for success. Although the presence of renal abnormality is used as a parameter in the Guy’s stone score, there is paucity of information about renal abnormalities for the STONE scoring system. In our study, we aimed to assess patientand procedurerelated factors related to outcomes of PNL in horseshoe kidneys. We observed that PNL procedures were more complicated due to the factors malrotation and ectopic location. We may consider that the upper pole is the

Fertility Issues in Pediatric Urology

Improved understanding of the pathogenesis and natural history of many urologic disorders, as well as advances in fertility preservation techniques, has increased the awareness of and options for management of fertility threats in pediatric patients. In children, fertility may be altered by oncologic conditions, by differences in sexual differentiation, by gonadotoxic drugs and other side effects of treatment for nonurologic disorders, and by urologic conditions, such as varicocele and cryptorchidism. Although fertility concerns are best addressed in a multidisciplinary setting, pediatric urologists should be aware of the underlying pathophysiology and management options to properly counsel and advocate for patients.

MP66-17 RISK FACTORS FOR REPEAT SURGICAL INTERVENTION IN PEDIATRIC NEPHROLITHIASIS: A PEDIATRIC HEALTH INFORMATION SYSTEM® DATABASE STUDY.

INTRODUCTION AND OBJECTIVES: The 2014 American Urologic Association cryptorchidism guidelines recommend abdominal orchiopexy for testes remaining non-palpable when examined under anesthesia after 6 months of age. Laparoscopic and open approaches are considered equivalent and dependent upon surgeon preference. We questioned whether immediate post-operative complications were comparable. METHODS: The American College of Surgeons National Surgical Quality Improvement Program data file was queried for laparoscopic (lap) and open orchiopexies of abdominal testes from 2012 2014. Data points included: age, ASA class, surgeon type, length of stay, operative time, complications, reoperation, and readmission. Statistical analyses included Student0s t-test and chisquare. RESULTS: A total of 1039 lap and 489 open abdominal orchiopexies were performed. Lap orchiopexy was performed even more commonly in 2013 (p1⁄40.018) and 2014 (p<0.001) than in 2012. There was no difference in ASA class between approaches. Pediatric urology performed the most orchiopexies (822 lap, 414 open), followed by pediatric surgery (126 lap, 52 open). Urology (63 lap, 19 open) and general surgery (23 lap, 0 open) performed fewer procedures. There was no difference in approach among the pediatric subspecialists (p1⁄40.294). Patients undergoing the lap approach were younger (mean 919.8 34.9 vs 1266.0 62.5 days, p<0.001). There was a trend towards lap surgeries being more commonly performed as outpatient (94.3% vs 91.2%, p1⁄40.08). The mean length of stay was shorter for lap patients (0.17 0.04 vs 0.48 0.20 days, p1⁄40.035), however open surgeries were shorter (73.7 3.0 vs 85.9 1.6 minutes, p<0.001). While the complication rate was low for both approaches (presented in the table), they were more than twice as likely to occur with the open approach (p1⁄40.03). There was no statistical difference in reoperation rate (0.3% lap vs 0.6% open) or readmission rate (1.2% lap vs 1.8% open). CONCLUSIONS: Although the open approach to abdominal orchiopexy takes less time to perform, the length of stay is longer. Immediate post-operative complications occur more commonly with the open approach, however the rate is low for both. Population studies into long term outcomes, such as failure or testicular loss, may offer further insight as to whether one approach is superior to the other.