Consultation on UTUC II Stockholm 2022: diagnostics, prognostication, and follow-up-where are we today?

PURPOSE: To summarise the current knowledge regarding diagnostics, prognostication and follow-up in upper tract urothelial carcinoma (UTUC). METHODS: A scoping review combined with expert opinion was applied to provide an overview of the current research field. Based on the published literature and the experts' own experience and opinions, consensus was reached through presentations and discussions at the meeting Consultation on UTUC II in Stockholm 2022. RESULTS: The strongest prognostic factors in UTUC are tumour grade and stage. They are correlated, and grade is used for indirect staging. The diagnostic examinations should include multiphase computed tomography urography (CTU) with corticomedullary phase, and urethrocystoscopy with cytology. If there is no clear diagnosis for clinical decision-making, ureterorenoscopy (URS) with focal cytology and biopsies should be performed. Both WHO classification systems (1973/1999 and 2004/2016) should be used. Novel biomarker tests are not yet widespread nor recommended for the detection of UTUC. Long-term, regular follow-up, including URS in patients who have had organ-sparing treatment, is important to check for tumour recurrences, intravesical recurrences, metastases and progression of the tumour. CONCLUSION: Proper diagnostics with correct grading of UTUC are necessary for appropriate treatment decisions. The diagnostics should include CTU with corticomedullary phase, urine or bladder cytology, URS with focal barbotage cytology, and biopsies when needed for proper diagnosis and risk stratification. Regular, long-term follow-ups are fundamental, due to the high rate of recurrence and risk of progression.

Cystinuria: clinical practice recommendation.

Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.

Non-contrast computed tomography characteristics in a large cohort of cystinuria patients.

PURPOSE: Cystine stones are widely considered hard and difficult to treat. Hounsfield Units (HU) are used in other stone types to estimate 'hardness' and treatments based on that finding. Our objective was to report mean HU of cystine stones in vivo in a large case series of cystinuria patients and assess for differences in genotype. METHODS: A prospective case series of cystinuria patients referred to a specialist centre was analysed. CT imaging was assessed by two independent radiologists to determine in vivo attenuation of cystine calculi. Mean HU was compared for both cystinuria genes (SLC3A1 and SLC7A9) using an independent t-test. RESULTS: 164 adult cystinuric patients were identified (55% male), median age 43 years (range 18-80). Median follow up was 31 months (IQR 10-62). Genetic data available for 153/164 (93%) demonstrated 97 SLC3A1 (63%) and 55 (36%) SLC7A9 mutations (39 homozygous, 16 heterozygous) and one heterozygous for both SLC3A1/SLC7A9. 107 patients had CT images available demonstrating calculi. Median HU across the cohort was 633 (5th to 95th centile 328-780). There was no difference in mean HU between SLC3A1 and SLC7A9 genotypes (p = 0.68) or homo and heterozygous SLC7A9 (p = 0.70). Mean HU correlated with stone size (Pearson correlation coefficient = 0.51, p < 0.001). CONCLUSION: In this large single centre cystinuria cohort, mean HU was low for stones that are difficult to treat. Calculi of < 800 HU should prompt consideration of a cystinuria diagnosis. Attenuation was not associated with genotype, and distinct 'smooth' and 'rough' stones were not observed. Calculi with HU > 1000 are unlikely pure cystine, and in a known cystinuric would suggest conversion to another stone type.

Consultation on kidney stones, Copenhagen 2019: aspects of intracorporeal lithotripsy in flexible ureterorenoscopy.

PURPOSE: To summarize current knowledge on intracorporeal laser lithotripsy in flexible ureterorenoscopy (fURS), regarding basics of laser lithotripsy, technical aspects, stone clearance, lithotripsy strategies, laser technologies, endoscopes, and safety. METHODS: A scoping review approach was applied to search literature in PubMed, EMBASE, and Web of Science. Consensus was reached through discussions at the Consultation on Kidney Stones held in September 2019 in Copenhagen, Denmark. RESULTS AND CONCLUSIONS: Lasers are widely used for lithotripsy during fURS. The Holmium laser is still the predominant technology, and specific settings for dusting and fragmenting have evolved, which has expanded the role of fURS in stone management. Pulse modulation can increase stone ablation efficacy, possibly by minimizing stone retropulsion. Thulium fibre laser was recently introduced, and this technology may improve laser lithotripsy efficiency. Small fibres give better irrigation, accessibility, and efficiency. To achieve optimal results, laser settings should be adjusted for the individual stone. There is no consensus whether the fragmentation and basketing strategy is preferable to the dusting strategy for increasing stone-free rate. On the contrary, different stone scenarios call for different lithotripsy approaches. Furthermore, for large stone burdens, all laser settings and lithotripsy strategies must be applied to achieve optimal results. Technology for removing dust from the kidney should be in focus in future research and development. Safety concerns about fURS laser lithotripsy include high intrarenal pressures and temperatures, and measures to reduce both those aspects must be taken to avoid complications. Technology to control these parameters should be targeted in further studies.

Development and content validation of the percutaneous nephrolithotomy assessment score.

OBJECTIVES: To develop and content validate a percutaneous nephrolithotomy assessment score, taking into consideration the procedure-specific risks. METHODS: This prospective international study utilized the Healthcare Failure Mode and Effect Analysis to systematically outline percutaneous nephrolithotomy and failure modes for each step. A total of 25 h was spent observing percutaneous nephrolithotomy carried out by six expert surgeons. Hazard analysis scoring was carried out by 11 experts. It was determined if the steps were single point weaknesses. Single point weaknesses and those assigned a hazard score ≥4 were included in the percutaneous nephrolithotomy assessment score. The tool was then content validated by 16 experts from 10 countries. RESULTS: Application of the Healthcare Failure Mode and Effect Analysis identified 64 failure modes; 37 failure modes had a hazard score ≥4. After adaptations based on expert feedback the final percutaneous nephrolithotomy assessment score was developed containing 10 phases, 21 processes and 47 subprocesses. All participants agreed that the tool contained pertinent procedural steps. CONCLUSIONS: This study has developed and shown the international content validity of a novel percutaneous nephrolithotomy assessment score. The tool can be utilized in modular operating room training to quantify operator progress, and can be used in conjunction with other modules as part of a complete percutaneous nephrolithotomy curriculum for trainees.

Dusting, fragmenting, popcorning or dustmenting?

PURPOSE OF REVIEW: The present review identifies the latest scientific investigations within the fields of fragmenting and dusting to discuss optimizing treatment. In addition, new settings such as 'popcorning' are scrutinized carefully. RECENT FINDINGS: During the past years, endoscopic techniques have continuously developed and changed the management of the treatment of kidney stones using ureteroscopy (URS). The most currently used energy source for stone disintegration is holmium laser lithotripsy. This technique offers different options for the surgeons to treat their patients suffering from kidney stones. SUMMARY: URS with the holmium laser allows surgeons to use a variety of different strategies for treating urinary stones. There are two techniques which are most frequently used within this field: firstly fragmenting, using low frequencies and high pulse energy to break stones into small fragments before removal. On the other hand, dusting has been popularized in the field of endourology in recent years. This uses high frequencies and low pulse energy to form fine dust particles which then pass spontaneously down the ureter.

Do stones still kill? An analysis of death from stone disease 1999-2013 in England and Wales.

OBJECTIVES: To analyse the trends in the number of deaths attributable to urolithiasis in England and Wales over the past 15 years (1999-2013). Urolithiasis has an estimated lifetime risk of 12% in males and 6% in females and is not perceived as a life-threatening pathology. Admissions with urinary calculi contribute to 0.5% of all inpatient hospital stays, and the number of deaths attributable to stone disease has yet to be identified and presented. MATERIALS AND METHODS: Office of National Statistics data relating to causes of death from urolithiasis, coded as International Classification of Diseases (ICD)-10 N20-N23, was collated and analysed for the 15-year period from 1999 to 2013 in England and Wales. These data were sub-categorised into anatomical location of calculi, age, and gender. RESULTS: In all, 1954 deaths were attributed to urolithiasis from 1999 to 2013 (mean 130.3 deaths/year). Of which, 141 were attributed to ureteric stones (mean 9.4 deaths/year). Calculi of the kidney and ureter accounted for 91% of all deaths secondary to urolithiasis; lower urinary tract (bladder or urethra) calculi contributed to only 7.9% of deaths. The data revealed an overall increasing trend in mortality from urolithiasis over this 15-year period, with an increase of 3.8 deaths/year based on a linear trend (R(2) = 0.65). Overall, the number of deaths in females was significantly higher than in males (ratio 1.5:1, P < 0.001); kidney and ureteric calculi causing death had a female preponderance (1.7:1, female:male); whereas calculi of the lower urinary tract was more common in males (1:2.2, female:male). CONCLUSIONS: Stone disease still causes death in the 21st century in England and Wales. This trend of increasing deaths must be placed in the context of the concurrent rising incidence of urolithiasis in the UK and the number of stone-related hospital episodes. The primary cause of death relating to complications of stone disease for each individual case should be further investigated to facilitate prevention of complications of urolithiasis.

Evolving Guidance on Ureteric Calculi Management in the Acute Setting.

Ureteric colic is a common presentation to acute emergency services. The gold standard test for the diagnosis of acute ureteric colic is a non-contrast computer tomography of the kidneys ureters and bladder (CT KUB). Non-steroidal anti-inflammatory drugs (NSAIDs) should be used as first-line analgesia, with studies showing that there is no role for steroid or phosphodiesterase-5 inhibitors. There is emerging evidence that a high body mass index (BMI) is a risk factor. The drugs used to facilitate stone passage are known as medical expulsive therapy (MET). The most evaluated being alpha-blockers. The Spontaneous Urinary Stone Passage Enabled by Drugs (SUSPEND) trial was designed to evaluate the use of MET (tamsulosin and nifedipine). This trial showed that there was no difference with MET and placebo for the spontaneous passage of ureteric stones. There is an emerging role for the use of primary ureteroscopy in the management of non-infective ureteric stones.

The genetic diversity of cystinuria in a UK population of patients.

OBJECTIVE: To examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype/phenotype correlation. PATIENTS AND METHODS: DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to identify the mutations in 74 patients in a specialist cystinuria clinic in the UK. Patients with type A cystinuria were classified into two groups: Group M patients had at least one missense mutation and Group N patients had two alleles of all other types of mutations including frameshift, splice site, nonsense, deletions and duplications. The levels of urinary dibasic amino acids, age at presentation of disease, number of stone episodes and interventions were compared between patients in the two groups using the Mann-Whitney U-test. RESULTS: In all, 41 patients had type A cystinuria, including one patient with a variant of unknown significance and 23 patients had type B cystinuria, including six patients with variants of unknown significance. One patient had three sequence variants in SLC7A9; however, two are of unknown significance. Three patients had type AB cystinuria. Three had a single mutation in SLC7A9. No identified mutations were found in three patients in either gene. There were a total of 88 mutations in SLC3A1 and 55 mutations in SLC7A9. There were 23 pathogenic mutations identified in our UK cohort of patients not previously published. In patients with type A cystinuria, the presence of a missense mutation correlated to lower levels of urinary lysine (mean [SE] 611.9 [22.65] vs 752.3 [46.39] millimoles per mole of creatinine [mM/MC]; P=0.02), arginine (194.8 [24.83] vs 397.7 [15.32] mM/MC; P<0.001) and ornithine (109.2 [7.40] vs 146.6 [12.7] mM/MC; P=0.02). There was no difference in the levels of urinary cystine (182.1 [8.89] vs 207.2 [19.23] mM/MC; P=0.23). CONCLUSIONS: We have characterised the genetic diversity of cystinuria in a UK population including 23 pathogenic mutations not previously published. Patients with at least one missense mutation in SLC3A1 had significantly lower levels of lysine, arginine, and ornithine but not cystine than patients with all other combinations of mutations.

Incidental renal stones in potential live kidney donors: prevalence, assessment and donation, including role of ex vivo ureteroscopy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Previously, donors with asymptomatic stones found incidentally on CT were not considered ideal donor candidates because of the presumed risk of morbidity to both the donor and recipient. Increasingly, studies show that these risks are low. This study aims to evaluate the long-term safety of using ex vivo ureteroscopy to remove the stones from the donor kidney on the bench before donation. Outcomes so far suggest that this technique can safely render a kidney stone-free before transplantation. This has led to 20 more transplants in our institution than would otherwise be possible. OBJECTIVES: To evaluate the prevalence of asymptomatic renal stones in our potential donor population. To assess the safety and success of ex vivo ureteroscopy (ExURS) to remove stones from explanted donor kidneys before transplantation. PATIENTS AND METHODS: We conducted a retrospective analysis of 377 computed tomography (CT) angiograms of potential kidney donors between October 2004 and May 2007 to assess the prevalence of asymptomatic renal stones in our donor population. Between October 2005 and October 2011, kidneys from suitable donors underwent ExURS. Stones were removed using basket extraction or were fragmented with holmium laser on bench before transplantation. Immediate and long-term complications of the transplanted recipients were recorded. Donors were followed with yearly ultrasonography of the remaining kidney in addition to standard follow-up protocol. RESULTS: Review of 377 CT angiograms between October 2004 to May 2007 showed a 5% prevalence of asymptomatic renal stones. Out of 55 potential donors (19 identified between October 2004 to May 2007 and a further 36 identified since May 2007), 20 donors with stones proceeded to donation, with stone size ranging from 2 to 12 mm. Of the patients, 17 proceeded to ExURS. Stones were removed in 10 patients; five with basket retrieval, four with laser fragmentation and one with both laser fragmentation and basket retrieval. There were no early or late allograft stone-related complications and no evidence of stones on follow-up imaging at a mean (range) of 10 (1-24) months. There has been no reported stone recurrence in any of the donors to date and no stone on ultrasonography of eight donors with >1-year follow-up (mean 26 months, range 12-49 months). CONCLUSIONS: Asymptomatic renal stones are present in 5% of our donors. ExURS can be safely used to remove stones in these kidneys before transplantation, without the risk of subjecting the donor to an additional stone-removing procedure. Continued long-term follow-up of donors and recipients is still required to ensure the safety of this approach.

A 9-year experience of renal injury at an Australian level 1 trauma centre.

OBJECTIVE: To detail the 9-year experience of renal trauma at a modern Level 1 trauma centre and report on patterns of injury, management and complications. PATIENTS AND METHODS: We analysed 338 patients with renal injuries who presented to our institution over a 9-year period. Data on demographics, clinical presentation, management and complications were recorded. RESULTS: Males comprised 74.9% of patients with renal injuries and the highest incidence was amongst those aged 20-24 years. Blunt injuries comprised 96.2% (n = 325) of all the renal injuries, with road trauma being the predominant mechanism accounting for 72.5% of injuries. The distribution of injury grade was; 21.6% grade 1 (n = 73), 24.3% grade 2 (n = 82), 24.9% grade 3 (n = 84), 16.6% grade 4 (n = 56), and 12.7% grade 5 (n = 43). Conservative management was successful in all grade 1 and 2 renal injuries, and 94.9%, 90.7% and 35.1% of grade 3, 4 and 5 injuries respectively. All but one of the 13 patients with penetrating injuries were successfully managed conservatively. CONCLUSIONS: Road trauma is the greatest cause of renal injury. Most haemodynamically stable patients are successfully managed conservatively.

The Endourological Society Inaugural Census Report.

The Endourological Society, the premier urologic society encompassing endourology, robotics, and focal surgery, is composed of a diverse group of >1300 urologists. However, limited information has been collected about society members. Recognizing this need, a survey was initiated to capture data regarding current member practices, as well as help the Society shape the future direction of the organization. Presented herein is the inaugural Endourological Society census report as the beginning of a continued effort for global improvement in the field of endourology. Using a REDCap® database, an email survey was circulated to the membership of the Endourological Society from May through June 2021. Twenty questions were posed, categorizing member data in terms of epidemiology/demographics, practice patterns, member opinions, and future educational preferences. Responses were received from 534 members, representing 40.3% of membership. Data demonstrated that the average age, gender, race, and ethnicity of the typical Society member respondent is a 48-year-old Caucasian male working in the United States, with a mean of 25 years in practice. Retrograde endoscopy and percutaneous nephrolithotomy were identified as the most common practice skills, and 50% of members are involved in robotics. Importantly, the census confirmed that the World Congress of Endourology and Technology remains popular with Society members as a means of educational advancement. To sustain and advance the Society, information is required to understand the career interests and future educational desires of its members. This inaugural census provides crucial data regarding its membership and how the Society can achieve continued success and adjust its focus. Future census efforts will expand on the initial findings and stratify the data to elucidate changes in the needs of the Society as a whole. Circulating an annual census will allow for continued improvements in the field of endourology and, ultimately, better care for urologic patients.