Assessing renal tissue temperature changes and perfusion effects during laser activation in an in vivo porcine model.

INTRODUCTION: High fluid temperatures have been seen in both in vitro and in vivo studies with laser lithotripsy, yet the thermal distribution within the renal parenchyma has not been well characterized. Additionally, the heat-sink effect of vascular perfusion remains uncertain. Our objectives were twofold: first, to measure renal tissue temperatures in response to laser activation in a calyx, and second, to assess the effect of vascular perfusion on renal tissue temperatures. METHODS: Ureteroscopy was performed in three porcine subjects with a prototype ureteroscope containing a temperature sensor at its tip. A needle with four thermocouples was introduced percutaneously into a kidney with ultrasound guidance to allow temperature measurement in the renal medulla and cortex. Three trials of laser activation (40W) for 60 s were conducted with an irrigation rate of 8 ml/min at room temperature in each subject. After euthanasia, three trials were repeated without vascular perfusion in each subject. RESULTS: Substantial temperature elevation was observed in the renal medulla with thermal dose in two of nine trials exceeding threshold for tissue injury. The temperature decay time (t½) of the non-perfused trials was longer than in the perfused trials. The ratio of t½ between them was greater in the cortex than the medulla. CONCLUSION: High-power laser settings (40W) can induce potentially injurious temperatures in the in vivo porcine kidney, particularly in the medullary region adjacent to the collecting system. Additionally, the influence of vascular perfusion in mitigating thermal risk in this susceptible area appears to be limited.

Change in renal blood flow in response to intrarenal pressure alterations induced by ureteroscopy in an in-vivo porcine model.

INTRODUCTION: High irrigation rates are commonly used during ureteroscopy and can increase intrarenal pressure (IRP) substantially. Concerns have been raised that elevated IRP may diminish renal blood flow (RBF) and perfusion of the kidney. Our objective was to investigate the real-time changes in RBF while increasing IRP during Ureteroscopy (URS) in an in-vivo porcine model. METHODS: Four renal units in two porcine subjects were used in this study, three experimental units and one control. For the experimental units, RBF was measured by placing an ultrasonic flow cuff around the renal artery, while performing ureteroscopy in the same kidney using a prototype ureteroscope with a pressure sensor at its tip. Irrigation was cycled between two rates to achieve targeted IRPs of 30 mmHg and 100 mmHg. A control data set was obtained by placing the ultrasonic flow cuff on the contralateral renal artery while performing ipsilateral URS. RESULTS: At high IRP, RBF was reduced in all three experimental trials by 10-20% but not in the control trial. The percentage change in RBF due to alteration in IRP was internally consistent in each porcine renal unit and independent of slower systemic variation in RBF encountered in both the experimental and control units. CONCLUSION: RBF decreased 10-20% when IRP was increased from 30 to 100 mmHg during ureteroscopy in an in-vivo porcine model. While this reduction in RBF is unlikely to have an appreciable effect on tissue oxygenation, it may impact heat-sink capacity in vulnerable regions of the kidney.

Quantification of outflow resistance for ureteral drainage devices used during ureteroscopy.

PURPOSE: Since renal pelvis pressure is directly related to irrigation flowrate and outflow resistance, knowledge of outflow resistance associated with commonly used drainage devices could help guide the selection of the type and size of ureteral access sheath or catheter for individual ureteroscopic cases. This study aims to quantitatively measure outflow resistance for different drainage devices utilized during ureteroscopy. METHODS: With measured irrigation flowrate and renal pelvis pressure, outflow resistance was calculated using a hydrodynamic formula. After placement of a drainage device into a silicone kidney-ureter model, a disposable ureteroscope with a 9.5-Fr outer diameter was inserted with its tip positioned at the renal pelvis. Irrigation was delivered through the ureteroscope from varying heights above the renal pelvis. Renal pelvis pressure was measured directly from the port of the kidney model using a pressure sensor (Opsens, Canada). Outflow resistance was determined by plotting flowrate versus renal pelvis pressure. All trials were performed in triplicate for each drainage device inserted. RESULTS: Flowrate was linearly dependent on renal pelvis pressure for all drainage devices tested. Outflow resistance values were 0.2, 1.1, 1.4, 3.9, and 6.5 cmH2O/[ml/min] for UAS 13/15 Fr, UAS 11/13 Fr, UAC 6 Fr, UAC 4.8 Fr, and UAC 4.0 Fr, respectively, across the range of commonly used irrigation flowrates. CONCLUSIONS: In this study, outflow resistance of different ureteral drainage devices was quantitatively measured. This knowledge can be useful when selecting which type and size of drainage device to insert to maintain safe renal pelvis pressure during ureteroscopy.

Development of an automated laser drilling algorithm to compare stone ablation patterns from different laser pulse modes.

PURPOSE: To develop a novel automated three-dimensional (3D) laser drilling algorithm to further investigate laser-stone interaction with different laser pulse modes. Comparison of post-ablative lattice architecture combined with mass of stone ablated can provide a more complete understanding of differences between pulse mode. METHODS: A 3D positioner (securing laser fiber) was programmed to create a 5 × 5 grid of drill holes spaced 1 mm apart on 15:5 cylindrical BegoStones. Beginning 0.5 mm above the stone surface, the laser fiber was activated and advanced 2 mm toward and into the stone for all 25 points. Four trials for each pulse mode [short pulse (SP), long pulse (LP), Moses Contact (MC), Moses Distance (MD)] were completed. Outcome measures were assessment of lattice preservation and mass of ablated stone. RESULTS: MC exhibited the greatest lattice preservation and least stone mass ablated (50.5 ± 2.2 mg). SP (69.4 ± 4.3 mg) and MD (70.0 ± 2.6 mg) had the greatest lattice destruction and stone mass ablated. The differences in stone ablated between MC and MD (p = 0.00003), MC and SP (p = 0.0002), and LP and MD (p = 0.004) were statistically significant. CONCLUSIONS: Consistent quantitative and qualitative differences between pulse modes were observed with a novel automated 3D laser drilling algorithm applied to BegoStone. The laser drilling algorithm developed here can be used to further enhance mechanistic understanding of laser-stone interactions and facilitate selection of appropriate laser pulse modes to balance precision and efficiency across the range of laser lithotripsy techniques.

Laser operator duty cycle effect on temperature and thermal dose: in-vitro study.

PURPOSE: High-power laser lithotripsy can elevate temperature within the urinary collecting system and increase risk of thermal injury. Temperature elevation is dependent on power settings and operator duty cycle (ODC)-the percentage of time the laser pedal is depressed. The objective of this study was to quantify temperature and thermal dose resulting from laser activation at different ODC in an in-vitro model. METHODS: Holmium laser energy (1800 J) was delivered at 30 W (0.5 J × 60 Hz) to a fluid filled glass bulb. Room temperature irrigation was applied at 8 ml/min. ODC was evaluated in 10% increments from 50-100%. Bulb fluid temperature was recorded and thermal dose calculated. Time to reach threshold of thermal injury and maximal allowable energy were also determined at each ODC. RESULTS: Upon laser activation, there was an immediate rise in fluid temperature with a "saw-tooth" oscillation superimposed on the curves for 50-90% ODC corresponding to periodic activation of the laser. Higher ODC resulted in greater maximum temperature and thermal dose, with ODC ≥ 70% exceeding threshold. Use of 50% compared to 60% ODC resulted in a tenfold increase in time required to reach threshold of thermal injury and an eightfold increase in maximal allowable energy. CONCLUSIONS: Laser activation at higher ODC produced greater fluid temperature and thermal dose. Time to threshold of thermal injury and maximal allowable energy were dramatically higher for 50% compared to 60% ODC at high-power settings. Proper management of laser ODC can enhance patient safety and optimize stone treatment.

Pulse modulation with Moses technology improves popcorn laser lithotripsy.

PURPOSE: Moses™ technology has been developed to improve holmium laser fragmentation at 1-2 mm distance from the stone. Because popcorn lithotripsy is a non-contact technique, we compared short pulse (SP) and Moses distance (MD) modes in an in vitro model. METHODS: BegoStones were fragmented using a 120 W Ho:YAG laser (P120 Moses) and a 230 µm core fiber introduced through a ureteroscope. 20 W (1 J × 20 Hz; 0.5 J × 40 Hz) and 40 W (1 J × 40 Hz; 0.5 J × 80 Hz) settings (total energy 4.8 kJ) were tested using SP and MD modes. We assessed fragment size distribution and mass lost in fluid (initial mass-final dry mass of all sievable fragments). High-speed video analysis of fragmentation strike rate and vapor bubble characteristics was conducted for 1 J × 20 Hz and 0.5 J × 80 Hz. Laser strike rate (number of strikes divided by frequency) was categorized as: (1) direct-a visual plume of dust ejected from stone while in contact with fiber tip; (2) indirect-a visual plume of dust ejected with distance between stone and fiber tip. RESULTS: For 1 J × 20 Hz (20 W), MD resulted in more mass lost in fluid and a lower distribution of fragments ≥ 2 mm compared to SP (p < 0.05). 0.5 J × 80 Hz (40 W) produced no fragments ≥ 2 mm, and there were no significant differences in fragment distribution between MD and SP (p = 0.34). When using MD at 1 J × 20 Hz, 96% of strikes were indirect vs 61% for SP (p = 0.059). In contrast to the single bubble of SP, with MD, there was forward movement of the collapsing second bubble, away from the fiber-tip. CONCLUSIONS: For lower frequency and power popcorn settings, pulse modulation results in more fragmentation through true non-contact laser lithotripsy.

Burnback: the role of pulse duration and energy on fiber-tip degradation during high-power laser lithotripsy.

High-power holmium lasers have become popular for ureteroscopic laser lithotripsy and dusting. Our aim was to investigate the effect of pulse duration and pulse energy on fiber-tip degradation when using high-power settings for popcorn lithotripsy. BegoStones were fragmented in a glass bulb to simulate renal calyx, using a 120 W Ho:YAG laser. A 242 µm fiber was placed via the ureteroscope 2 mm distance from stones (popcorn model). To assess the effect of pulse duration on fiber-tip degradation, long pulse (LP) and short pulse (SP) settings were compared at settings of 1.0Jx20Hz (20 W), 0.5Jx70Hz (35 W), and 1.0Jx40Hz (40 W). To assess the effect of pulse energy on tip degradation, 40 W SP settings (0.5Jx80Hz, 0.8Jx50Hz, and 1.0Jx40Hz) were tested. Pulse duration was measured using a photodetector and peak power was then calculated using the pulse duration and pulse energy. Experiments were conducted for 4 min. Fiber-tip length was measured before and after using a digital caliper. Fiber-tip degradation was least when using LP for all settings tested (p < 0.01). For 40 W settings, tip degradation was significantly lower when using a pulse energy of 0.5 J compared to 0.8 J or 1.0 J (p < 0.004). LP mode results in less fiber burnback for all power settings tested. Total power is more important than frequency in the development of burnback. However, high-power 40 W settings can be utilized with less burnback if lower pulse energies are used. Understanding these parameters can improve the longevity of the laser fiber and improve procedural efficiency.

Outcomes of renal calculi in patients with spinal cord injury.

AIMS: Patients with spinal cord injury (SCI) are at risk of developing renal calculi. This study describes the management of renal calculi among patients with SCI with attention to factors influencing surgical management vs observation. METHODS: This retrospective, cohort study identified patients with SCI and renal calculi between 2009 to 2016 from an institutional neurogenic bladder database and detailed the management of their stones. A stone episode was defined as radiographic evidence of new calculi. RESULTS: Of 205 patients with SCI, 34 had renal stones, for a prevalence of 17%. The mean age was 50 years (range 22,77) and most had cervical SCI (n = 22, 65%). There were 41 stone episodes with 98 individual stones identified with a mean stone size of 4.9 mm (range 1-19). Of the 41 episodes, 10 (24%) underwent surgery after initial diagnosis. Pain was the most common primary indication for surgery (n = 9, 60%). The median time from diagnosis to intervention for all patients was 4 months (interquartile range 1,23). Of the 41 episodes, 31 (76%) were initially observed and among these, 5 ultimately required surgery (16%) while 26 (84%) did not. Of these 26, 12 (46%) stones passed spontaneously and 14 (53%) remained unchanged. The need for surgery correlated with more stone episodes (P = .049). CONCLUSION: In this cohort of patients with SCI and small, nonobstructing renal stones, 76% (n = 31) were offered observation. Of these observed patients, 84% (n = 26) did not require further intervention at a median of 4 years of follow-up.

Enhanced shockwave lithotripsy with active cavitation mitigation.

The goal of this study was to examine acoustical mechanisms that manipulate cavitation events in order to improve the efficacy of shockwave lithotripsy (SWL) at higher rates. Previous work has shown that applying low amplitude acoustic pulses immediately after each shockwave (SW) can force cavitation bubbles to coalesce and enhance SWL efficacy. In this study, the effects of applying low amplitude acoustic pulses at different time delays is investigated before and after each SW, which would result in different interactions among residual microbubbles producing forced coalescence and dispersion. Utilizing forced coalescence and dispersion was hypothesized to mitigate the shielding effect of residual bubbles, further improving efficacy particularly for higher SWL rates. A set of in vitro experiments was performed in a water tank so that the behavior of bubbles, coalescence and dispersion, could be observed with a high-speed camera. Model kidney stones were treated by a clinical Dornier lithotripter with firing rates of 30 shocks/min and 120 shocks/min, along with an in-house made transducer to generate low amplitude acoustic pulses fired at different pressures and time delays. The average percentage of untreated stone fragments greater than 2 mm was 15.81% for 120 shocks/min without mitigation and significantly reduced to 0.19% for the optimum mitigation protocol.

New technologies in benign prostatic hyperplasia management.

PURPOSE OF REVIEW: Surgical debulking of the adenoma/transition zone has been the fundamental principle which underpins transurethral resection of the prostate - still acknowledged to be the gold-standard therapy for benign prostatic hyperplasia (BPH). However, there has been a recent resurgence in development of new BPH technologies driven by enhanced understanding of prostate pathophysiology, development of new ablative technologies, and the need for less morbid alternatives as the mean age and complexity of the treatment population continues to increase. The objective of this review is to highlight new BPH technologies and review their available clinical data with specific emphasis on unique features of the technology, procedural effectiveness and safety, and potential impact on current treatment paradigms. RECENT FINDINGS: New technologies have emerged that alter the shape of the prostate to decrease urinary obstruction and enhance delivery of a lethal thermal dose by steam injection into the transition zone of the prostate. Energy can be delivered to the prostate via a beam of high-pressure saline or focused acoustic energy to mechanically disintegrate prostate tissue. Methods of cell death are being targeted with selectivity by the arterial supply with embolization and specific to prostate cells via injectable biological therapies. SUMMARY: A number of new technologies are at various stages of development and improve on the transurethral resection of the prostate paradigm by moving closer to the ideal BPH therapy which is definitive, can be performed in minutes, in the office setting, with only local anesthesia and oral sedation.

Histotripsy methods in mechanical disintegration of tissue: towards clinical applications.

In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumours, kidney stone fragmentation, enhancing anti-tumour immune response, and tissue decellularisation for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilise different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of non-invasive surgery.

Ureteroscopy for nephrolithiasis in transplanted kidneys.

INTRODUCTION: While percutaneous nephrolithotomy (PCNL) is often the procedure of choice for renal and ureteral calculi in transplant kidneys, retrograde ureteroscopy (URS) is a less frequently applied but excellent option if stone burden is small. We retrospectively examined nine surgical cases performed in seven patients in what appears to be the largest single institutional series reported to date. MATERIALS AND METHODS: Seven patients underwent nine retrograde URS between June of 2009 and September of 2013, by two endourologists. These cases were reviewed retrospectively. RESULTS: Among the nine procedures, we were able to address the stone(s) endoscopically in seven. Among these procedures, laser lithotripsy was used in six cases, and basket stone extraction was applied in four procedures. Ureteral stents were placed following six procedures with ureteral access and treatment. Postoperative imaging revealed the patient to be stone free after five of the seven procedures with ureteral access and treatment. There were two postoperative urinary tract infections, and no major complications. Of the nine total procedures, six were outpatient, two were followed by observation stay < 24 hours, and one patient was admitted > 24 hours. Among the two failures, one underwent PCNL and the other had percutaneous nephrostomy (PNT) placed but expired from unrelated causes prior to the intended PCNL. CONCLUSIONS: Retrograde URS with laser lithotripsy and/or basket extraction is a reasonable option for treating small renal transplant stones, with most patients in our series being discharged as outpatients, having complete stone clearance and avoiding PCNL.

Histotripsy of the prostate using a commercial system in a canine model.

PURPOSE: Histotripsy is a focused ultrasound technology that uses controlled acoustic cavitation to homogenize targeted tissue. We assessed local and systemic effects after histotripsy treatment with the Vortx RX® system in a canine model. The system was not approved for human use at the time of the study. MATERIALS AND METHODS: Histotripsy was applied in 10 intact male dogs. The therapy transducer (36 elements, 700 kHz and 11 cm focal distance) delivered acoustic bursts (3 cycles and 500 Hz pulse repetition frequency) transabdominally to the prostate for 60 minutes. Tissue and systemic response were assessed by transrectal ultrasound, cystoscopy and interval evaluation of blood and urine parameters. Prostates were harvested on postoperative day 2 in 2 dogs and on postoperative day 28 in 8. RESULTS: A treatment cavity was apparent in each prostate on transrectal ultrasound and cystoscopy. Mean prostate volume decreased 36% (range 19% to 53%) by postoperative day 28. Although clinical symptoms were not produced, notable pathological findings at necropsy consisted of rectal wall muscle degeneration in 2 animals and concern for a potential histotripsy effect and 1 cm diameter areas of fibrosis in the abdominal rectus muscle in 2 animals suggestive of thermal injury along the acoustic propagation path to the prostate. CONCLUSIONS: Extracorporeal application of histotripsy produced prostate debulking in all dogs. Pathological findings of collateral injury are of concern since this may represent suboptimal confinement of cavitation or heating of overlying tissue. Further study is under way to quantify the prefocal thermal fields to eliminate these effects before human application.

Expulsive therapy versus early endoscopic stone removal in patients with acute renal colic: a comparison of indirect costs.

PURPOSE: While medical expulsive therapy is associated with lower health care expenditures compared to early endoscopic stone removal in patients with renal colic, little is known about the effect of medical expulsive therapy on indirect costs. MATERIALS AND METHODS: Using a previously validated claims based algorithm we identified a cohort of patients with acute renal colic. After determining the up-front treatment type (ie an initial course of medical expulsive therapy vs early endoscopic stone removal) we compared differences in rates of short-term disability filing. We used propensity score matching to account for differences between treatment groups such that patients treated with medical expulsive therapy vs early endoscopic stone removal were similar with regard to measured characteristics. RESULTS: In total, 257 (35.8%) and 461 (64.2%) patients were treated with medical expulsive therapy or early endoscopic stone removal, respectively. There were no differences between treatment groups after propensity score matching. In the matched cohort the patients treated with medical expulsive therapy had a 6% predicted probability of filing a claim for short-term disability compared to 16.5% in the early endoscopic stone removal cohort (p <0.0001). Among the patients who filed for short-term disability those prescribed medical expulsive therapy had on average 1 fewer day of disability than those treated surgically (0.9 vs 1.8 days, p <0.001). CONCLUSIONS: An initial trial of medical expulsive therapy is associated with significantly lower indirect costs to the patient compared to early endoscopic stone removal. These findings have implications for providers when counseling patients with acute renal colic.

Prostate histotripsy: evaluation of prostatic urethral treatment parameters in a canine model.

OBJECTIVE: To assess the impact of histotripsy treatment parameters (pulse number and pulse-repetition frequency [PRF]) on the efficiency of histotripsy induced homogenisation of the prostatic urethra. MATERIALS AND METHODS: In all, 34 transabdominal prostate histotripsy treatments were applied along a perpendicular plane traversing the prostatic urethra of 21 dogs. Prostate histotripsy was applied with (i) escalating pulse number with fixed PRF or (ii) at fixed pulse number with varying PRFs. The development of urethral homognisation ≤14 days of histotripsy was evaluated endoscopically and confirmed histologically. RESULTS: Within 14 days of histotripsy 50%, 83%, 83%, and 100% of dogs receiving 12 500, 25 000, 50 000, and 100 000 pulses/mm of treatment path (delivered at 500 Hz PRF), respectively developed prostatic urethral disintegration. Delivery of 100 000 pulses/mm was required to achieve urethral disintegration in all dogs within 24 h of histotripsy treatment. Increasing histotripsy PRF from 50 to 500 to 2000 Hz while applying a constant dose of 25 000 pulses/mm treatment was associated with increased rate of urethral disintegration (50% vs 75% vs 100% at 14 days, respectively). CONCLUSIONS: Increasing the number of histotripsy pulses and/or increasing the PRF of histotripsy treatment applied to the urethra may improve the rate and efficiency of prostatic urethral disintegration in the canine model. This understanding will aid in the development of treatment strategies for prostate histotripsy for benign prostatic hyperplasia in human trials.

Development and translation of histotripsy: current status and future directions.

PURPOSE OF REVIEW: The aim of this article is to outline the initial development of histotripsy, a noninvasive image-guided focused ultrasound technology that mechanically homogenizes targeted tissues and to describe the results of preclinical translational research directed toward urologic applications. RECENT FINDINGS: Histotripsy tissue ablation is based on initiation and control of acoustic cavitation at a target point within the body. This unique mechanical mechanism of action is distinct when compared with conventional thermal ablative modalities. Features of histotripsy (nonthermal, noninvasive, high precision, real-time monitoring/feedback, and tissue liquefaction) have prompted assessment of this technology as a potential ablative therapy for a number of organs and disease processes. SUMMARY: Ongoing research efforts to apply histotripsy to preclinical models of benign prostatic hyperplasia, prostate cancer, renal masses, and renal calculi have resulted in enhanced understanding of cavitation bioeffects, refinement of treatment systems, strategies to enhance treatment efficiency, and initiation of a pilot human clinical trial to assess the safety of histotripsy for benign prostatic hyperplasia therapy.

Hand-assisted and standard laparoscopic radical nephrectomy after prior renal surgery.

INTRODUCTION: With the increasing use of partial nephrectomy, cases of ipsilateral tumor recurrence will inevitably occur. We aimed to evaluate the efficacy and feasibility of laparoscopic radical nephrectomy (LRN) for a previously operated kidney, through a case-matched comparison with LRN in patients without prior renal surgery. MATERIALS AND METHODS: Among 550 patients who underwent hand-assisted or standard LRN at our institution between August 1996 and January 2013, we identified patients who had prior laparoscopic or open surgical renal surgery. Each study patient was matched 1:2 with patients who had not had prior renal surgery. Matching was exact by surgical approach, gender, side of surgery, and American Society of Anesthesiologists score, and closest possible by age and body mass index. RESULTS: LRN was performed in 9 patients (6 hand-assisted and 3 standard) with prior open surgical or laparoscopic renal surgery. There were no conversions to open surgery. Primary surgeon tended to be to attending urologist more often than the trainee in the study compared to the control patients, an indication of increased technical difficulty. Additionally, there were four intraoperative injuries recorded in the study group (44%) and just one such event in the control group (5.6%) (p = 0.0297). CONCLUSIONS: Although LRN after prior renal surgery is challenging, requiring the expertise of experienced surgeons and being associated with appreciable rate of intraoperative injuries, these cases can be completed laparoscopically (especially with the selective use of hand-assistance) and are associated with duration of hospitalization and postoperative complication rates similar to those in patients undergoing LRN without prior renal surgery.

Kidney stone growth through the lens of Raman mapping.

Bulk composition of kidney stones, often analyzed with infrared spectroscopy, plays an essential role in determining the course of treatment for kidney stone disease. Though bulk analysis of kidney stones can hint at the general causes of stone formation, it is necessary to understand kidney stone microstructure to further advance potential treatments that rely on in vivo dissolution of stones rather than surgery. The utility of Raman microscopy is demonstrated for the purpose of studying kidney stone microstructure with chemical maps at ≤ 1 µm scales collected for calcium oxalate, calcium phosphate, uric acid, and struvite stones. Observed microstructures are discussed with respect to kidney stone growth and dissolution with emphasis placed on < 5 µm features that would be difficult to identify using alternative techniques including micro computed tomography. These features include thin concentric rings of calcium oxalate monohydrate within uric acid stones and increased frequency of calcium oxalate crystals within regions of elongated crystal growth in a brushite stone. We relate these observations to potential concerns of clinical significance including dissolution of uric acid by raising urine pH and the higher rates of brushite stone recurrence compared to other non-infectious kidney stones.

A novel canine model for prostate cancer.

BACKGROUND: No existing animal model fully recapitulates all features of human prostate cancer. The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer. Canine prostate cancer features many similarities with its human counterpart. We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models. METHODS: The Ace-1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs. Tumor progression was monitored by TRUS imaging. Some dogs were subjected to positron emission tomography (PET) for tumor detection. Time of euthanasia was determined based on tumor size, impingement on urethra, and general well-being. Euthanasia was followed by necropsy and histopathology. RESULTS: Ace-1 tumor cells grew robustly in every dog injected. Tumors grew in subcapsular and parenchymal regions of the prostate. Tumor tissue could be identified using PET. Histological findings were similar to those observed in human prostate cancer. Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors. CONCLUSIONS: We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis.