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.

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.

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.

Hypertension and renal impairment in patients with cystinuria: findings from a specialist cystinuria centre.

Higher blood pressures (mean systolic difference 16.8 mmHg) when compared to matched individuals are already reported in patients with calcium urolithiasis. We present the prevalence of hypertension and renal impairment in patients with cystinuria from our specialist single centre. We analysed our prospective database of adult patients with cystinuria who attend our cystinuria service. This included details of the medical and operative management of their disease. Descriptive statistics were used to analyse and present the data. 120 patients were included with a median age of 40 (19-76) years, 66 were male (55%) and 54 were female (45%). 54/120 patients (45%) were taking medications to prevent stone formation. 78% (94/120) patients reported having undergone one or more stone-related procedure. 59% (55/94) of these having required at least one PCNL or open procedure during their lifetime. Prevalence of hypertension was 50.8% (61/120), and double in males compared to females (62.1% vs. 37.0%, P = 0.0063). Mean baseline creatinine was 88.2 (49-153) µmol/l and eGFR was 77.6 (32-127) ml/min/1.73 m2. When categorized by CKD stage, only 24.6% (27% vs. 21%, M vs. F) patients had normal renal function (being an eGFR > 89 ml/min/1.73 m2). 57.6% patients were CKD stage 2 and 17.8% CKD stage 3. Females had a slightly greater incidence of renal impairment. All patients who have previously undergone a nephrectomy (n = 10) or have a poorly functioning kidney (n = 19) have renal impairment (CKD stage 2 or 3). Incidence of hypertension in patients with cystinuria is 51%, with a male preponderance. Only 25% of patients with cystinuria have normal renal function. This highlights the long-term cardiovascular and renal risks that the metabolic effects of cystinuria pose, in addition to the challenges of managing recurrent urolithiasis in a young population.

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.

Learning Curves in Urolithiasis Surgery: A Systematic Review.

BACKGROUND AND AIMS: Procedures for urolithiasis are a core part of the development for the urologist in training. Understanding the learning curve of the procedures is important, allowing for planning in the training and assessment of trainees. The aim of this study was to systematically review the literature pertaining to learning curves in urolithiasis surgery. MATERIALS AND METHODS: The review was registered on the PROSPERO database and conducted in keeping with the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. Embase, MEDLINE, and PsycINFO were systematically searched from inception to January 2018, with a reference review conducted. All empirical studies on learning curves in urolithiasis surgery were included irrespective of procedure. Articles describing pediatric surgery, nontechnical skills in surgery, or those not written in English were excluded. RESULTS: Of 390 articles identified from screening, a final 18 studies were included. Fourteen studies identified the learning curve in percutaneous nephrolithotomy. These studies identified a learning curve of between 30 and 60 cases for both operative time (OT) and complication rates. Four articles focused on flexible ureteroscopy (FURS); the learning curve for FURS has been outlined as 60 cases for OT and 56 cases for fragmentation efficacy. CONCLUSIONS: The complexities of determining learning curves are extensive; studies use different parameters to measure outcomes and observe skill acquisition rates of surgeons with differing prior experience. Evidence in this article can guide trainee urologists with regard to the expected rate of progress. Multi-operator multicenter research utilizing standard outcome measures should be conducted to establish definitive learning curves.

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.

Percutaneous Nephrolithotomy: Update, Trends, and Future Directions.

CONTEXT: Percutaneous nephrolithotomy (PCNL) is the surgical standard for treating large or complex renal stones. Since its inception, the technique of PCNL has undergone many modifications. OBJECTIVE: To perform a collaborative review on the latest evidence related to outcomes and innovations in the practice of PCNL since 2000. EVIDENCE ACQUISITION: A literature review was performed using the PubMed database between 2000 and July 2015, restricted to human species, adults, and the English language. The Medline search used a strategy including the following keywords: percutaneous nephrolithotomy, PNL, advances, trends, technique, and the Medical Subject Headings term percutaneous nephrostomy. EVIDENCE SYNTHESIS: Population-based studies have now provided a wealth of information regarding patient outcomes following PCNL. The complexity of the stone treated can be quantified using a variety of validated nephrolithometry classification systems. Increasing familiarity with the supine approach to PCNL has enabled simultaneous combined retrograde and antegrade surgery. Advances such as endoscopic guided percutaneous access may help urologists achieve access with less morbidity. Increasing miniaturization of equipment has led to the development of mini, micro, and ultramini techniques. The tubeless method of PCNL is now accepted practice with good evidence of safety in appropriately selected patients. CONCLUSIONS: Modern-day PCNL allows personalized stone management tailored to individual patient and surgeon factors. Future studies should continue to refine methods to assess complexity and safety and to determine consensus on the use of miniaturized PCNL. PATIENT SUMMARY: Modern-day percutaneous nephrolithotomy has transformed from an operation traditionally undertaken in one position, using one access method with one set of instrumentation and one surgeon, to one with a variety of options at each step.

Can the Presence of Crystalluria Predict Stone Formation in Patients with Cystinuria?

OBJECTIVES: To determine the feasibility of crystalluria as a biomarker for stone disease in patients with cystinuria. PATIENTS AND METHODS: All patients attending a multidisciplinary cystinuria clinic provided early morning urine (EMU) and clinic urine (CU) samples for crystal measurement over a 2-year period (August 1, 2010, to July 31, 2012). Association between presence of crystals, presence of stone(s), and new stone growth (NSG) was determined using the chi-square test. Crystal numbers in EMU and CU were compared in patients with stones/NSG and no stones/stable disease using the Mann-Whitney U test. RESULTS: There was a statistically significant difference between the presence of crystalluria and presence of stones for CU (chi-square test = 5.86, df = 1, p = 0.02) but not EMU (chi-square test = 1.92, df = 1, p = 0.17) and between the presence of crystalluria and NSG for CU (chi-square test = 8.10, df = 1, p = 0.004) but not EMU (chi-square test = 1.32, df = 1, p = 0.25). Patients with stones and NSG have higher levels of crystalluria in CU than patients with no stones or stable disease (stones, median = 41, interquartile range [IQR] = 600 vs median = 0, IQR = 21, p = 0.01; NSG, median = 49, IQR = 525 vs median = 0, IQR = 40, p = 0.01). CONCLUSION: The presence of crystalluria in CU samples is associated with the presence of stones. Crystalluria is comparable to ultrasound and may serve as a useful adjunct to predict whether a patient with cystinuria has stones, which could guide the frequency of clinic review and imaging.

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.