Ex-vivo ureteroscopy, laser lithotripsy, and stone basketing extraction of deceased donor kidney stones during machine perfusion preservation.

The incidence of nephrolithiasis in kidney donors is rare. The timing and treatment of nephrolithiasis in deceased donor kidneys are not well established. While some programs have proposed ex-situ rigid or flexible ureteroscopy treatment before transplantation, we report on two cases of kidney stones in the same deceased donor that we treated by flexible ureteroscopy and laser lithotripsy performed during the storage time on a hypothermic perfusion machine. Two deceased donor kidneys were found to have multiple kidney stones discovered on preprocurement CT imaging. The right kidney had less than five 2-3 mm stones, whereas the left had five to ten 1 mm stones with a single 7 mm stone. Both organs were placed on a hypothermic perfusion machine and maintained at a temperature of 4°C. An ex-vivo flexible ureteroscopy with laser lithotripsy and basket extraction was performed while the kidneys were maintained on Lifeport* perfusion machine. The cold ischemia time was 16.9 and 23.1 h. After 12 months of observational follow-up, neither recipient had nephrolithiasis, UTI, or other urologic complications. The creatinine values now are 1.17 and 2.44 mg/dL (103.4 and 215.7 µmol/L), respectively. Ex-vivo flexible ureteroscopy with laser lithotripsy and stone removal on machine-perfused kidneys appears to be safe and offers a good option to treat graft nephrolithiasis and prevent posttransplant complications. Ureteroscopy serves as a minimally invasive treatment option with direct stone removal. Performing this while on machine perfusion minimizes the ischemic time of the kidney and resultant complications or delays in graft function.

Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant.

Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the current classification of skeletal disorders, the disease is included in the group of bone fragility disorders along with osteogenesis imperfecta. The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis-the main lipid component of the plasma membrane essential for bone mineralization. To date, 15 patients from eight families with CDL with bone fragility have been described in the literature, and a recurrent variant c.148C>T (p.Arg50Ter) in the SGMS2 gene has been identified, which was found in patients from six families. We diagnosed the disease in 11 more patients from three unrelated families, caused by the same heterozygous nonsense variant c.148C>T (p.Arg50Ter) in the SGMS2 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the SGMS2 gene, the presence of which must be taken into consideration in the diagnosis of the disease. The primary analysis of this variant will contribute to optimal molecular genetic diagnostics, which can reduce diagnostic costs and time.

Efficacy of Intramuscular Ketorolac for Preventing Renal Colic Post Stent Removal: Randomized Controlled Trial.

PURPOSE: The treatment of stones ureteroscopically is associated with postoperative pain, thought to be due largely to the use of ureteral stents. In some, stent removal precipitates renal colic that can last from minutes to hours. We sought to determine if intramuscular ketorolac could reduce post-stent removal renal colic. MATERIALS AND METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial assessing the effects of ketorolac administered at time of stent removal. Patients were randomized to receive an intramuscular ketorolac 30 mg or placebo immediately prior to stent removal. Patients were contacted 1 and 7 days after stent removal to assess pain, need for opioids, emergency department or clinic visits and the need for surgical/medical interventions. RESULTS: A total of 124 patients (62 patients each in the control and treatment groups) were included in the study. The groups were comparable in demographic/operative characteristics. No difference in mean pain scores or proportion of patients who experienced severe pain at 1 and 7 days post stent removal was detected between groups. However, use of ketorolac resulted in significantly fewer renal colic-related unplanned emergency department/clinic visits in the treatment group (2%) compared with the control group (13%, p=0.032). CONCLUSIONS: Although administration of ketorolac prior to stent removal does not significantly reduce overall subjective pain experienced post stent removal compared to placebo, it does reduce the likelihood of severe renal colic requiring emergency department or office visits. Eligible patients may benefit from routine use of ketorolac injection at the time of stent removal.

Expression of Small Noncoding RNAs in Urinary Exosomes Classifies Prostate Cancer into Indolent and Aggressive Disease.

PURPOSE: This is the first report of the development and performance of a platform that interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes. The Sentinel™ PCa Test classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel CS Test stratifies patients with prostate cancer between those with low risk prostate cancer (Grade Group 1) from those with intermediate and high risk disease (Grade Group 2-5), and the miR Sentinel HG Test stratifies patients with prostate cancer between those with low and favorable intermediate risk prostate cancer (Grade Group 1 or 2) and those with high risk (Grade Group 3-5) disease. MATERIALS AND METHODS: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.0 microarrays. Using proprietary selection and classification algorithms, informative sncRNAs were selected to customize an interrogation OpenArray™ platform that forms the basis of the tests. The tests were validated using a case-control sample of 1,436 subjects. RESULTS: The performance of the miR Sentinel PCa Test demonstrated a sensitivity of 94% and specificity of 92%. The Sentinel CS Test demonstrated a sensitivity of 93% and specificity of 90% for prediction of the presence of Grade Group 2 or greater cancer, and the Sentinel HG Test demonstrated a sensitivity of 94% and specificity of 96% for the prediction of the presence of Grade Group 3 or greater cancer. CONCLUSIONS: The Sentinel PCa, CS and HG Tests demonstrated high levels of sensitivity and specificity, highlighting the utility of interrogation of urinary exosomal sncRNAs for noninvasively diagnosing and classifying prostate cancer with high precision.

Ten-Year Outcomes of Renal Tumor Radio Frequency Ablation.

PURPOSE: We reviewed long-term oncologic outcomes in patients with renal tumors treated with radio frequency ablation more than 10 years ago. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with renal tumors who underwent radio frequency ablation from November 2000 to August 2007. Demographic, clinical and radiological data were assessed to determine evidence of disease recurrence. Patients with familial renal cell carcinoma syndromes were excluded from study. We calculated disease-free, metastasis-free, cancer specific and overall survival with the Kaplan-Meier method. Subgroup analysis of patients who had at least 10 years followup was performed to determine actual 10-year survival. Analysis was also performed based on tumor size. RESULTS: A total of 112 tumors in 106 patients were treated with radio frequency ablation. Median followup was 79 months (IQR 28.9-121.1) and mean ± SD tumor size was 2.5 ± 0.8 cm. Initial technical success was achieved in 97% of cases. There were 10 recurrences. Kaplan-Meier 6-year disease-free and cancer specific survival rates were 89% and 96%, respectively. Disease-free survival decreased to 68% for tumors greater than 3 cm. In the subgroup with at least 10-year followup the actual disease-free, cancer specific and overall survival rates were 82%, 94% and 49%, respectively. No patient experienced recurrence after 5 years. CONCLUSIONS: Radio frequency ablation is a safe and effective treatment option for small renal masses less than 3 cm in diameter. We report good oncologic outcomes with actual 10-year survival data. No recurrence developed after 5 years. Tumors greater than 3 cm have significantly poorer outcomes.

Comparison of Robot-Assisted Versus Open Simple Prostatectomy for Benign Prostatic Hyperplasia.

PURPOSE OF REVIEW: Recent advancements in minimally invasive approaches for prostate surgery have provided numerous options for surgical management of benign prostatic hyperplasia (BPH). In the setting of a large prostate, an open simple prostatectomy was previously considered the gold standard surgical treatment. However, the recently updated American Urological Association (AUA) guidelines on surgical management of BPH now consider both open and minimally invasive approaches to simple prostatectomy viable alternatives for treating large glands, depending on expertise with the techniques. The purpose of our review is to discuss the minimally invasive robot-assisted approach and compare it to the classic open approach to simple prostatectomy. RECENT FINDINGS: Despite longer operative times, the robotic approach is associated with shorter hospital stay and lower morbidity profile. The morbidity of an open approach remains significant. Blood transfusions are 3-4 times as likely compared to a robotic approach and major complications are twice as likely. Consistent with previous literature, our review shows functional outcome improvements like flow rate and symptom score to be comparable between the robotic and open approach. The amount of adenoma resected and PSA decline is also similar among robotic and open cases. Robot-assisted simple prostatectomy is a safe and effective procedure for BPH secondary to a large prostate gland. Appropriately, it is no longer deemed "investigational" by the latest AUA guidelines on BPH and recommended as an alternative to the open approach.

Axial Abdominal Imaging after Partial Nephrectomy for T1 Renal Cell Carcinoma Surveillance.

PURPOSE: The overall recurrence rate of T1 renal cell carcinoma is low. We evaluated abdominal imaging after partial nephrectomy based on current guidelines for T1 renal cell carcinoma surveillance. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with T1 renal cell carcinoma who underwent partial nephrectomy between 2006 and 2012 followed by abdominal imaging at our institution. Primary and secondary outcomes were the incidence and timing, respectively, of imaging diagnosed abdominal recurrences. A literature review was performed to summarize prior reports of recurrence incidence and timing after partial nephrectomy for T1 disease. RESULTS: A total of 160 patients with stage T1a and 37 with T1b underwent partial nephrectomy. Seven patients had an abdominal recurrence, including 3 with local and distant recurrences, and 4 with a metachronous contralateral kidney recurrence. The incidence of abdominal recurrence detected by imaging was higher in the T1b than in the T1a group (10.8% vs 1.9%, p = 0.024). Although it was not significant, median time to recurrence was earlier in T1b vs T1a cases (13 vs 37 months, p = 0.480). In each group recurrences developed after 3 years of suggested guideline surveillance. In the literature combined with the current study the time to median recurrence for T1b vs T1a was 24 vs 29 months (p = 0.226). CONCLUSIONS: Recurrences detected by abdominal imaging developed earlier and more frequently in T1b than in T1a cases. Future recommendations for surveillance strategies after partial nephrectomy should distinguish T1a from T1b with less intense frequency of imaging for T1a. A longer period of surveillance should be considered since recurrences can develop beyond 3 years.

Epidemiology of stone disease across the world.

Nephrolithiasis is a highly prevalent disease worldwide with rates ranging from 7 to 13% in North America, 5-9% in Europe, and 1-5% in Asia. Due to high rates of new and recurrent stones, management of stones is expensive and the disease has a high level of acute and chronic morbidity. The goal of this study is to review the epidemiology of stone disease in order to improve patient care. A review of the literature was conducted through a search on Pubmed®, Medline®, and Google Scholar®. This review was presented and peer-reviewed at the 3rd International Consultation on Stone Disease during the 2014 Société Internationale d'Urologie Congress in Glasgow. It represents an update of the 2008 consensus document based on expert opinion of the most relevant studies. There has been a rising incidence in stone disease throughout the world with a narrowing of the gender gap. Increased stone prevalence has been attributed to population growth and increases in obesity and diabetes. General dietary recommendations of increased fluid, decreased salt, and moderate intake of protein have not changed. However, specific recommended values have either changed or are more frequently reported. Geography and environment influenced the likelihood of stone disease and more information is needed regarding stone disease in a large portion of the world including Asia and Africa. Randomized controlled studies are lacking but are necessary to improve recommendations regarding diet and fluid intake. Understanding the impact of associated conditions that are rapidly increasing will improve the prevention of stone disease.

Irreversible electroporation of small renal masses: suboptimal oncologic efficacy in an early series.

PURPOSE: To report on the first short-term oncologic outcomes of percutaneous irreversible electroporation for small renal masses. METHODS: Patients with cT1a renal masses treated with irreversible electroporation from April 2013 through December 2016 were reviewed. Small, low complexity tumors were generally selected for irreversible electroporation using the NanoKnife® System (Angiodynamics, Latham, NY, USA). Surveillance imaging was performed post-operatively, and survival analysis was completed using the Kaplan-Meier method. RESULTS: A total of 42 tumors in 41 patients underwent irreversible electroporation. Mean tumor size was 2.0 cm with a median R.E.N.A.L nephrometry score of 5. Twenty-nine patients (71%) were discharged the same day of the procedure and no major (Clavien grade II or higher) intraoperative or post-operative complications occurred. Initial treatment success rate was 93%; our three failures (7%) underwent salvage radiofrequency ablation. With a mean follow-up of 22 months, 2-year local recurrence-free survival was 83% for patients with biopsy confirmed renal cell carcinoma, 87% with biopsy confirmed or a history of renal cell carcinoma, and 92% for the intent-to-treat cohort. CONCLUSIONS: Although with low morbidity, in comparison to extirpation and conventional thermal ablation technologies, irreversible electroporation has suboptimal short-term local disease control results in this series of small, low complexity tumors. Larger series and longer follow-up will determine the durability of this modality.

How I do it: percutaneous radiofrequency ablation (RFA).

Percutaneous radiofrequency ablation has seen increased utilization secondary to the rising incidence of renal cell carcinoma. This has been shown to be an effective and durable treatment especially in the elderly comorbid patient. In this article, we describe our technique and factors related to successful outcomes.

Cancer control of partial nephrectomy for high-risk localized renal cell carcinoma: population-based and single-institutional analysis.

PURPOSE: Cancer control of partial nephrectomy for high-risk localized renal cell carcinoma is unclear. To assess whether PN provides adequate cancer control in high-risk disease (HRD), survival outcomes were compared in both a population-based cohort and an institutional cohort. METHODS: Surveillance, Epidemiology, and End Results database and a prospectively maintained institutional database were queried for patients with RCC who underwent PN or RN for a localized tumor ≤7 cm and were found to have high-grade and/or high-stage disease (HRD). Cancer-specific (CSS) or recurrence-free survival (RFS) and overall survival (OS) were primary outcomes measured and were compared between those who underwent PN and RN using multivariable Cox proportional hazards and propensity analysis. RESULTS: The population cohort consisted of 12,757 (24.9 %) patients with HRD, 85.2 and 14.8 % of which underwent RN and PN, respectively. RN was not associated with CSS (HR 1.23, p = 0.08) but was independently associated with poor OS (HR 1.16, p = 0.031). Propensity analysis showed that RN resulted in a 20 % increased risk of death from all causes (p = 0.008). In the institutional cohort, of 317 patients, 35.9 % had HRD, 56 and 52 of which underwent RN and PN, respectively. Adjusting for age-adjusted Charlson index, RN was a predictor of poor OS (OR 6.20, p = 0.041). Propensity analysis showed that RFS and OS were not related to nephrectomy type (RN HR 0.65, p = 0.627 and RN HR 1.70, p = 0.484). CONCLUSIONS: In patients with pathologic high-risk RCC, partial excision is associated with similar cancer control as compared to radical excision.

Options for independent bladder management in patients with spinal cord injury and hand function prohibiting intermittent catheterization.

AIMS: Choosing the appropriate bladder management strategy for the spinal cord injury patient with neurogenic bladder and hand function prohibitive of self catheterization (urethral or stomal) catheterization is complex and based on limited literature. We have catalogued the available data in this review. METHODS: A literature review was conducted on external sphincterotomy, suprapubic tube, ileal conduit, and ileovesicostomy between 1994 and 2012. Articles on neurogenic bladder focused primarily on spinal cord injury were included. Important aspects of each technique, patient selection, urologic events, and quality of life are described. CONCLUSION: The available literature consists primarily of level 3 data. Patient reported outcomes were rarely measured. External sphincterotomy is a good option for males who are candidates for an external catheter and who wish to avoid a complicated reconstruction-most will need re-operations for failure. Suprapubic tube is an option in both genders. Complaints usually involve urine leakage and urinary tract infection, which typically resolve with conservative measures. There is some evidence to support patient satisfaction. Ileal conduit is an option for all patients with quadriplegia, offering continuous drainage and absence of foreign material. Many providers and patients will choose more conservative options first. The ileovesicostomy is best applied to small bladders with severe overactivity. The "reversibility" of this procedure makes it attractive to those not interested in an ileal conduit and who have had complications from prolonged suprapubic tube placement. The authors conclude with recommendations for future research, most importantly more standard reporting of objective data.

Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia Treatments: Implications for Clinical Trials.

Placebo medications and sham surgeries have long been thought to be inert treatments. These groups served as a threshold to which an active treatment should be compared in a randomized trial to determine the true efficacy of the active treatment. However, surprising changes in subjective symptom scores and objective measures of voiding have been demonstrated in numerous placebo medication or sham surgery arms of trials. The exact mechanisms by which these inactive treatments augment patient outcomes are not clearly defined and multiple theories have been proposed to explain the often pronounced response. It appears that urologic outcomes are particularly prone to these effects and the astute physician should keep these responses in mind when interpreting any trial on a new therapy.

Perinephric fat stranding is associated with increased age and stone size but not with serum creatinine in patients with obstructing ureterolithiasis.

Previous reports show increased severity of perinephric fat stranding (PFS) with elevated serum creatinine in obstructing ureterolithiasis. We sought to investigate this association with our institution's patient population.We reviewed charts of patients diagnosed with obstructive ureterolithiasis or nephrolithiasis in our emergency department between January and October 2018. Patient demographics, lab results, and computed tomography (CT) imaging were reviewed. A blinded radiologist reviewed all CTs and graded hydronephrosis and PFS. Subjects were stratified by degree of PFS and compared via paired t-test, chi-squared test, univariate analysis, and multivariate analysis.We identified 141 patients; 114 had no-mild (Group 1) PFS, while 27 had moderate-severe (Group 2) PFS. Group 1 had a mean age of 56 (SD = 16.1) and mean stone size of 7.3 mm (SD = 4.22); 77% of the cohort had symptoms under 24 h. Group 2 was older with a mean age of 65 (SD = 16.2, p = 0.01) and mean stone size of 10.1 mm (SD = 6.07, p < 0.01); 50% had symptoms less than 24 h (p = 0.01). PFS did not correlate with change in serum creatinine. Univariate and multivariate analysis showed increasing age increased the odds of moderate-severe PFS by 3.5% (OR = 1.035, p < 0.05) while increased stone size increased the odds of moderate-severe PFS by 13.7% (OR = 1.137, p = 0.01).Although increased PFS correlated with increased age and stone size, no correlation was found with presenting creatinine or change in creatinine. Degree of PFS is likely a poor predictor of renal disease severity in acute ureterolithiasis.

Needle Aligned Ultrasound Image-Guided Access Through Dual-Segment Array.

Ultrasound (US) guided access for percutaneous nephrolithotomy (PCNL) is gaining popularity in the urology community as it reduces radiation risk. The most popular technique involves manual image-needle alignment. A misaligned needle however needs to be retracted and reinserted, resulting in a lengthened operation time and complications such as bleeding. These limitations can be mitigated through the co-registration between the US array and needle. The through-hole array concept provides the primary solution, including a hole at the center of the array. Because of the central opening, the image-needle alignment is achieved inherently. Previous literature has described applications that are limited to superficial and intravascular procedures, suggesting that developing a through-hole array for deeper target applications would be a new breakthrough. OBJECTIVE: Here, we present a dual-segment array with a central opening. As the prototype development, two segments of 32-element arrays are combined with an open space of 10 mm in length in between them. METHOD: We conducted phantom and ex-vivo studies considering the target depth of the 80-100 mm range. The image quality and needle visibility are evaluated by comparing the signal-to-noise ratio (SNR), full width at half maximum (FWHM), and contrast-to-noise ratio (CNR) results measured with a no-hole linear array under equivalent conditions. An ex-vivo study is performed using porcine kidneys with ceramic balls embedded to evaluate the needle access accuracy. RESULTS AND CONCLUSION: The mean needle access error of 20 trials is found to be 2.94 ±1.09 mm, suggesting its potential impact on realizing a simple and intuitive deep US image-guided access.

Single-port robotic-assisted simple prostatectomy is associated with decreased post-operative narcotic use in a propensity score matched analysis.

Robotic-assisted simple prostatectomy (RASP) has proven to be an effective minimally invasive option for benign prostatic enlargement (BPE) in recent years. Single-site surgery is theorized to reduce post-operative pain beyond traditional minimally invasive approaches. We sought to assess whether use of a single-port robotic platform decreases post-operative opioid use in patients undergoing robotic-assisted simple prostatectomy (RASP). A retrospective review was performed of all patients undergoing RASP our institution from November 2017 to July 2019. Demographic, intraoperative, and post-operative data, including morphine equivalent (ME) use, were collected. Patients were stratified by robotic platform utilized. Propensity score matching using nearest neighbor method was performed using prostate volume, Charlson comorbidity index (CCI), and post-op ketorolac use in 4:1 fashion. Chi-squared analysis and Kruskal-Wallis analyses were utilized. Two-hundred-and-seven men underwent RASP. After matching, 80 patients (64 multi-port, 16 single-port) were included in the analysis. Groups were comparable for age, body mass index, CCI, prostate volume, prior opioid use, and use of scheduled ketorolac post op. The single-port approach was associated with a reduction in MEs once admitted to the floor (5 vs. 11 mg, p = 0.025) and an increase in the proportion of patients who did not require any narcotics post-operatively (44 vs. 19%, p = 0.036). In a propensity matched cohort of patients undergoing RASP at a single institution, use of the single-port robotic system conferred a significant decrease in post-operative narcotic use by approximately 50%.

Irreversible Electroporation for Renal Ablation Does Not Cause Significant Injury to Adjacent Ureter or Bowel in a Porcine Model.

Objective: To evaluate the safety of irreversible electroporation (IRE) for renal ablation adjacent to the ureter or bowel. Materials and Methods: Six adult pigs each underwent bilateral IRE of the kidney. To simulate adjacence, the left proximal ureter and duodenum were secured onto the left and right kidney capsule, respectively. Two IRE probes were placed into the renal parenchyma and configured to bridge the ureter and bowel. Therapeutic IRE was delivered at 2000 V/cm for 70 pulses in both forward and reverse polarity. The animal was survived and euthanized at 1, 3, or 14 days. Histopathology was obtained for all potentially injured bowel and ureteral segments. Retrograde pyelogram (RPG) was performed on each left-sided ureter. Results: Histologic analysis of the ureter identified reactive changes at the level of the periureteral adipose tissue, which progressed from acute inflammation on day 1 to focal fibrosis by day 14. Urothelial mucosa and surrounding smooth muscle layers were unaffected at all time points. RPGs did not show any abnormalities in all specimens. Histologic analysis of the bowel demonstrated acute inflammation in the serosa and subserosal tissue on day 1. Three days after IRE, inflammation and crypt abscesses were focally present in the deep aspects of the bowel mucosa. Inflammation in the mucosal layer resolved 14 days after IRE. Conclusions: In a porcine model of renal IRE, no significant injury was apparent after intentional ablation adjacent to the ureter and bowel. IRE may be a safe alternative to thermal ablation for tumors near the ureter or bowel.

Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target.

A compact accelerator-based neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. An original design tandem accelerator is used to provide a proton beam. The proton beam energy can be varied within a range of 0.6-2.3 MeV, keeping a high-energy stability of 0.1%. The beam current can also be varied in a wide range (from 0.3 mA to 10 mA) with high current stability (0.4%). In the device, neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction. A beam-shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. A lot of scientific research has been carried out at the facility, including the study of blistering and its effect on the neutron yield. The BNCT technique is being tested in in vitro and in vivo studies, and the methods of dosimetry are being developed. It is planned to certify the neutron source next year and conduct clinical trials on it. The neutron source served as a prototype for a facility created for a clinic in Xiamen (China).