Renal stone detection using a low kilo-voltage paediatric CT protocol - a porcine phantom study.

INTRODUCTION: Reducing tube voltage is an effective dose saving method in computed tomography (CT) assuming tube current is not concurrently increased. Recent innovations in scanner technology now enable CT tube voltage reduction to 70 kV thereby increasing opportunities for dose reduction in paediatric patients, but it is unclear if the increased image noise associated with 70 kV impacts on ability to visualise renal stones accurately. The purpose was to assess detectability of nephrolithiasis using a bespoke paediatric phantom and low kV, non-contrast CT and to assess inter-observer agreement. METHODS: Forty-two renal stones of different size and chemical composition were inserted into porcine kidneys and positioned in a bespoke, water-filled phantom mimicking a 9-year-old child weighing approximately 33kg. The phantom was scanned using 120 and 70 kV CT protocols, and the detectability of the stones was assessed by three radiologists. Absolute agreement and Fleiss' kappa regarding detectability were assessed. RESULTS: The mean diameter of renal stones as measured physically was 4.24 mm ranging from 1 to 11 mm. Four stones were missed by at least one observer. One observer had a sensitivity of 93 and 95% at 70 and 120 kV, respectively, while the sensitivity for observers 2 and 3 was 98% at both kV levels. Specificity was 100% across readers and kV levels. Absolute agreement between the readers at 70 kV was 92% (kappa = 0.86) and 98% (kappa = 0.96) at 120 kV indicating a strong agreement at both kV levels. CONCLUSIONS: The results suggest that lowering the kV does not affect the detection rate of renal stones and may be a useful dose reduction strategy for assessment of nephrolithiasis in children.

Consultation on kidney stones, Copenhagen 2019: lithotripsy in percutaneous nephrolithotomy.

PURPOSE: To evaluate the balance between existing evidence and expert opinions on the safety and efficacy of new technological improvements in lithotripsy techniques for percutaneous nephrolithotomy (PCNL). METHODS: A scoping review approach was applied to search literature in Pubmed, Embase, and Web of Science. Consensus by key opinion leaders was reached at a 2-day meeting entitled "Consultation on Kidney Stones: Aspects of Intracorporeal Lithotripsy" held in Copenhagen, Denmark, in September 2019. RESULTS: New-generation dual-mode single-probe lithotripsy devices have shown favourable results compared with use of ballistic or ultrasonic lithotripters only. However, ballistic and ultrasonic lithotripters are also highly effective and safe and have been the backbone of PCNL for many years. Compared with standard PCNL, it seems that mini PCNL is associated with fewer bleeding complications and shorter hospital admissions, but also with longer operating room (OR) time and higher intrarenal pressure. Use of laser lithotripsy combined with suction in mini PCNL is a promising alternative that may improve such PCNL by shortening OR times. Furthermore, supine PCNL is a good alternative, especially in cases with complex renal stones and large proximal ureteric stones; in addition, it facilitates endoscopic combined intrarenal surgery (ECIRS). CONCLUSION: Recent technological improvements in PCNL techniques are promising, but there is a lack of high-level evidence on safety and efficacy. Different techniques suit different types of stones and patients. The evolution of diverse methods has given urologists the possibility of a personalized stone approach, in other words, the right approach for the right patient.

Can Dual Energy CT with Fast kV-Switching Determine Renal Stone Composition Accurately?

RATIONALE AND OBJECTIVES: To determine whether a single source computed tomography (CT) system utilizing fast kV switching and low dose settings can characterize (diameter and chemical composition) renal stones accurately when compared infrared spectroscopy. MATERIALS AND METHODS: The chemical composition of 15 renal stones was determined using Fourier transform infrared spectroscopy. The stones were inserted into a porcine kidney and placed within a water tank for CT scanning using both fast kV switching dual energy and standard protocols. Effective atomic number of each stone was measured using scanner software. Stone diameter measurements were repeated twice to determine intra-rater variation and compared to actual stone diameter as measured by micro CT. RESULTS: The chemical composition of three stones (one calcium phosphate and two carbonite apatite) could not be determined using the scanner software. The composition of 10/12 remaining stones was correctly identified using dual energy computed tomography (83% absolute agreement; k = 0.69). No statistical difference (p = 0.051) was noted in the mean stone diameter as measured by clinical CT and micro CT. CONCLUSION: Dual energy computed tomography using fast kV switching may potentially be developed as a low dose clinical tool for identifying and classifying renal stones in vivo supporting clinical decision-making.

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

Circulating miRNAs in localized/locally advanced prostate cancer patients after radical prostatectomy and radiotherapy.

BACKGROUND: Overtreatment is a well-known clinical challenge in local prostate cancer (PCa). Although risk assessment models have contributed to a better stratification of patients with local PCa, a tailored management is still in its infancy. Over the last few decades, microRNAs (miRNAs) have shown promising results as biomarkers in PCa. The aim of this study was to investigate circulating miRNAs after management of local PCa. METHODS: The relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma from 149 newly diagnosed patients with local or locally advanced PCa. Real-time polymerase chain reaction was used for analysis. A baseline sample at time of diagnosis and a follow-up sample after 6 months were assessed. The patients were grouped in an interventional cohort (radical prostatectomy, curative intent radiotherapy, or androgen-deprivation therapy alone) and an observational cohort (watchful waiting or active surveillance). RESULTS: In the interventional cohort, levels of both miRNA-93 and miRNA-221 were significantly lower in the follow-up samples compared to baseline z = -2.738, P = 0.006, and z = -4.498, P < 0.001, respectively. The same observation was recorded for miRNA-125b in the observational cohort (z = -2.656, P = 0.008). Both miRNA-125b and miRNA-221 were correlated with risk assessment r = 0.23, P = 0.015, and r = 0.203, P = 0.016 respectively, while miRNA-93 showed tendency to significant correlation with the prostatectomy Gleason score (r = 0.276, P = 0.0576). CONCLUSIONS: The current results indicate a possible role of miRNA-93 and miRNA-221 in disease monitoring in localized and locally advanced PCa. Larger studies are warranted to assess the clinical impact of these biomarkers.

Anatomic variations and stone formation.

PURPOSE OF REVIEW: The pathophysiological mechanisms in kidney stone formation are insufficiently understood. In order to achieve a better understanding of the complexity of stone formation, studies evaluating anatomical variations in the renal papillae have been performed. This review intends to illuminate recent findings. Moreover, new techniques to improve the understanding and interpretation of crystallization mechanisms are reviewed. RECENT FINDINGS: Due to improvements of digital ureteroscopes, detailed endoscopic mapping of renal papillae is now possible. Connections between papillary morphology and histopathological changes in different subsets of stone formers have been documented. The formation of kidney stones seems to take place in relation to Randall's plaques, Ducts of Bellini or by free formation. Additionally, theories of kidney stone formation because of vascular injury or inflammatory events in the papillae have been suggested. SUMMARY: Novel techniques including improved digital endoscopic visualization, microcomputed tomography (CT), electron microscopy and energy dispersive compositional analyses of kidney stones seem essential in the search for effective and reliable methods to understand stone forming processes, which ultimately should result in effective measures for more personalized stone prevention strategies in the future.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

This corrects the article DOI: 10.1038/bjc.2017.429.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

The evaluation of radiologic methods for access guidance in percutaneous nephrolithotomy: a systematic review of the literature.

INTRODUCTION: Percutaneous nephrolithotomy (PNL) is the treatment of choice for larger and complex renal calculi. First step in performing PNL is to obtain access to the renal cavity using either fluoroscopy or ultrasound (US) guidance or a combination of both. Which guiding method to choose is controversial? A systematic review of the literature was performed comparing image guidance modalities for obtaining access in PNL. Evidence acquisition and synthesis: A PubMed, Scopus and Cochrane search for peer-reviewed studies was performed using the keywords "ultrasound" AND "fluoroscopy" AND "Percutaneous nephrolithotomy". Eligible articles were reviewed according to PRISMA criteria. Two hundred and forty records were identified using the keywords. Of these twelve studies were considered relevant. RESULTS: US guidance seems to be associated with a slightly lower complication rate, which may be related to fewer puncture attempts needed for obtaining access and to better peri-renal organ visualization. On the other hand, US-guidance alone needs the adjunct of fluoroscopy in a significant number of cases for achieving access. Stone free rate (SFR) was comparable between groups. Using US for renal access unequivocally reduces radiation exposure. CONCLUSION: Current evidence indicates that both fluoroscopy and US guidance may be successfully used for obtaining percutaneous renal access. Combining the image-guiding modalities - US and fluoroscopy - seems to increase outcome in PNL both with regard to success in achieving access and reducing complications. Furthermore, including US in the access strategy of PNL reduces radiation exposure to surgeon and staff as well as patients.

Risks of flexible ureterorenoscopy: pathophysiology and prevention.

Currently, indications for flexible ureterorenoscopy (fURS) are expanding, mainly due to technological advancements. Although data from clinical series definitely presents fURS as a safe procedure, serious complications including sepsis and ureteral lesions do occur. These complications seem to be a result of the unique elements of fURS, ureteral access and irrigation, pushing normal upper urinary tract physiology into pathophysiological processes, including intrarenal/pyelo-veneous backflow and ureteral contractions, potentially resulting in septic, haemorrhagic and ureteral lesional complications. Knowledge on normal upper urinary tract physiology are crucial for understanding how these harmful effects of fURS may be avoided or minimized. The pathophysiology of intrarenal pressure increases and ureteral access will be discussed as a basis for understanding preventive measures. Role of antibiotics, ureteral access sheaths, safty guidewires, pain medication, prestenting and pharmacologic modulation of pyeloureteral dynamics are reviewed from a pathophysiological perspective.

Testicular microlithiasis is associated with ethnicity and socioeconomic status.

BACKGROUND: There are limited studies about testicular microlithiasis (TML) and background information such as health, lifestyle, and socioeconomic status. PURPOSE: To assess the prevalence of TML in relation to socioeconomic status and ethnicity. MATERIAL AND METHODS: From a database of scrotal ultrasound examinations in a single institution, all men who underwent routine ultrasound examinations for a variety of symptoms from 1998 to 2015 were included. Skilled observers performed all examinations, and presence of any form of intra-testicular calcification, including TML, was recorded on the examination report and a representative image obtained and stored. A total of 1105 cases with TML were reviewed and random sample of 1105 controls from the same database was also reviewed. Demographics were recorded including ethnicity (white, black, and others) and socioeconomic groups (IMD Quintile). RESULTS: Black men had increased prevalence of TML (odds ratio [OR] = 2.17, 95% confidence interval [CI] = 1.72-2.75) compared with white men. Among the 1105 TML cases, 423 (38.3%) were white, 273 (24.7%) black, 152 (13.8%) had other ethnicities, and 257 (23.2%) had no ethnicity recorded. In the control group of 1105 men without TML, 560 (50.7%) were white, 171 (15.5%) black, 111 (10.0%) had other specified ethnicities, and 263 (23.8%) had no ethnicity recorded. Men from the most deprived socioeconomic groups had higher prevalence of TML than men in the most affluent groups, with a trend in OR from the least deprived to the most deprived group. CONCLUSION: Pathogenesis and clinical relevance of TML is unknown but our results point towards possible ethnic and socioeconomic variation in the underlying causes of TML.

Rigid-only versus combined rigid and flexible percutaneous nephrolithotomy: a systematic review.

INTRODUCTION: Percutaneous nephrolithotomy (PNL) is usually performed worldwide with a rigid-only antegrade approach. Daily practice suggests that adding flexible nephroscopy and/or ureteroscopy to conventional rigid PNL might improve its efficacy and safety, but available evidence is weak. Appraisal of reliable outcomes of such PNL techniques would better guide intraoperative choices and optimize surgical results. Therefore, our objective was to systematically review relevant literature comparing the outcomes of rigid-only PNL and combined flexible PNLs (adding flexible nephroscopy and/or flexible ureteroscopy) for the treatment of large and/or complex upper urinary tract calculi, with regard to efficacy and safety. EVIDENCE ACQUISITION: Ovid MedLine, PubMed, Scopus and Web of Science databases were searched in August 2016 to identify relevant studies. Article selection was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis criteria. EVIDENCE SYNTHESIS: Six articles reporting on 666 patients were included: two randomized controlled trials, two retrospective comparative studies and two case series ≥50 patients (one prospective and one retrospective). A narrative synthesis of minor evidences was also prepared. The adjunct of flexible nephroscopy and/or ureteroscopy provided better stone-free rates (range 86.7-96.97%), through a single percutaneous access most of the times and in any position, reducing the need for second-look procedures. Safety of the combined flexible procedures was improved to a variable degree, with a consensual reduction of the mean hospital stay (range 5.1-7 days). CONCLUSIONS: The current evidence suggests that patients with large and/or complex urolithiasis might benefit from the adjunct of flexible nephroscopy and/or ureteroscopy to rigid PNL.

Effect of Low-Energy Linear Shockwave Therapy on Erectile Dysfunction-A Double-Blinded, Sham-Controlled, Randomized Clinical Trial.

INTRODUCTION: Previous studies have shown that focal low-energy extracorporeal shockwave therapy (Li-ESWT) can have a positive effect in men with erectile dysfunction (ED). Linear Li-ESWT (LLi-ESWT) for ED has not been previously assessed in a randomized trial. AIM: To evaluate the treatment outcome of LLi-ESWT for ED. METHODS: Men with ED (n = 126) and a score lower than 25 points on the International Index of Erectile Function erectile function domain (IIEF-EF) were included. Subjects were allocated to receive LLi-ESWT once a week for 5 weeks or sham treatment once a week for 5 weeks. After a 4-week break, the two groups received active treatment once a week for 5 weeks. Subjects completed the IIEF, Erection Hardness Scale (EHS), Sexual Quality of Life-Men, and the Erectile Dysfunction Inventory of Treatment Satisfaction at baseline, after 9 weeks, and after 18 weeks. MAIN OUTCOME MEASURES: The primary outcome measurement was an increase of at least five points on the IIEF-EF score. The secondary outcome measurement was an increased EHS score to at least 3 in men with a score no higher than 2 at baseline. Data were analyzed by linear and logistic regression. RESULTS: Mean IIEF-EF scores were 11.5 at baseline (95% CI = 9.8-13.2), 13.0 after five sessions (95% CI = 11.0-15.0), and 12.6 after 10 sessions (95% CI = 11.0-14.2) in the sham group and correspondingly 10.9 (95% CI = 9.1-12.7), 13.1 (95% CI = 9.3-13.4), and 11.8 (95% CI = 10.1-13.4) in the ESWT group. Success rates based on IIEF-EF score were 38.3% in the sham group and 37.9% in the ESWT group (odds ratio = 0.95, 95% CI = 0.45-2.02, P = .902). Success rates based on EHS score were 6.7% in the sham group and 3.5% in the ESWT group (odds ratio = 0.44, 95% CI = 0.08-2.61, P = .369). A limitation of this study is that device settings (number of shockwaves and penetration depth) were estimated based on an existing trial on focused ESWT. CONCLUSION: No clinically relevant effect of LLi-ESWT on ED was found.

Quality Assessment of Urinary Stone Analysis: Results of a Multicenter Study of Laboratories in Europe.

After stone removal, accurate analysis of urinary stone composition is the most crucial laboratory diagnostic procedure for the treatment and recurrence prevention in the stone-forming patient. The most common techniques for routine analysis of stones are infrared spectroscopy, X-ray diffraction and chemical analysis. The aim of the present study was to assess the quality of urinary stone analysis of laboratories in Europe. Nine laboratories from eight European countries participated in six quality control surveys for urinary calculi analyses of the Reference Institute for Bioanalytics, Bonn, Germany, between 2010 and 2014. Each participant received the same blinded test samples for stone analysis. A total of 24 samples, comprising pure substances and mixtures of two or three components, were analysed. The evaluation of the quality of the laboratory in the present study was based on the attainment of 75% of the maximum total points, i.e. 99 points. The methods of stone analysis used were infrared spectroscopy (n = 7), chemical analysis (n = 1) and X-ray diffraction (n = 1). In the present study only 56% of the laboratories, four using infrared spectroscopy and one using X-ray diffraction, fulfilled the quality requirements. According to the current standard, chemical analysis is considered to be insufficient for stone analysis, whereas infrared spectroscopy or X-ray diffraction is mandatory. However, the poor results of infrared spectroscopy highlight the importance of equipment, reference spectra and qualification of the staff for an accurate analysis of stone composition. Regular quality control is essential in carrying out routine stone analysis.

A Model-Based Approach for Joint Analysis of Pain Intensity and Opioid Consumption in Postoperative Pain.

Joint analysis of pain intensity and opioid consumption is encouraged in trials of postoperative pain. However, previous approaches have not appropriately addressed the complexity of their interrelation in time. In this study, we applied a non-linear mixed effects model to simultaneously study pain intensity and opioid consumption in a 4-h postoperative period for 44 patients undergoing percutaneous kidney stone surgery. Analysis was based on 748 Numerical Rating Scale (NRS) scores of pain intensity and 51 observed morphine and oxycodone dosing events. A joint model was developed to describe the recurrent pattern of four key phases determining the development of pain intensity and opioid consumption in time; (A) Distribution of pain intensity scores which followed a truncated Poisson distribution with time-dependent mean score ranging from 0.93 to 2.45; (B) Probability of transition to threshold pain levels (NRS ≥ 3) which was strongly dependent on previous pain levels ranging from 2.8-15.2% after NRS of 0-2; (C) Probability of requesting opioid when allowed (NRS ≥ 3) which was strongly correlated with the number of previous doses, ranging from 89.8% for requesting the first dose to 26.1% after three previous doses; (D) Reduction in pain scores after opioid dosing which was significantly related to the pain intensity at time of opioid request (P < 0.001). This study highlights the importance of analyzing pain intensity and opioid consumption in an integrated manner. Non-linear mixed effects modeling proved a valuable tool for analysis of interventions that affect pain intensity, probability of rescue dosing or the effect of opioids in the postoperative pain period.

The new concept of ureteral access sheath with guidewire disengagement: One wire does it all.

PURPOSE: To prospectively evaluate the new Flexor©Parallel™ Rapid Release™ (Cook(®), Bloomington, IN, USA) access sheath (UAS) which allows the use of a single wire to serve as both safety and working guide. MATERIALS AND METHODS: Between June and September 2014, adult patients from five European centers who underwent flexible ureteroscopy (fURS) for therapeutic and diagnostic purposes were included. The 12/14Fr Flexor©Parallel™ UAS was evaluated. Data were collected and examined by both univariate and multivariate analyses. The UAS material and usage characteristics were rated per case by the surgeons on a scale from very bad to very good. RESULTS: In total, 134 UASs were used in 67 male and 67 female patients. Fifty percent of ureters (67 patients) were pre-stented. Ninety percent of the procedures were therapeutic. The overall successful insertion rate was 94 %. Pre-stenting status was the only independent factor for a successful access sheath insertion: 98.5 % of the pre-stented patients had a successful UAS placement vs. 82 % of non-pre-stented (p = 0.001, C.I. 95 %: 1.2). Evaluation of the material and radiopacity was considered very good in over 90 % of cases. Release of the guidewire, hydrophilic coating, gliding of the endoscope and repeatability were considered very good in over 80 %. There were two (1.4 %) UAS malfunctions and one submucosal lesion reported. CONCLUSIONS: The use of the Flexor©Parallel™ Rapid Release™ (Cook(®), Bloomington, IN, USA) with usage of a single guidewire in a prospective multicentric scenario was clinically applicable in the majority of cases. Pre-stenting increased the chance of a successful insertion from 82 to 98.5 %.