Follow-up of urolithiasis patients after treatment: an algorithm from the EAU Urolithiasis Panel.

OBJECTIVE: To develop a follow-up algorithm for urinary stone patients after definitive treatment. MATERIALS AND METHODS: The panel performed a systematic review on follow-up of urinary stone patients after treatment (PROSPERO: CRD42020205739). Given the lack of comparative studies we critically evaluated the literature and reached a consensus on the follow-up scheme. RESULTS: A total of 76 studies were included in the analysis, including 17 RCTs. In the stone-free general population group, 71-100% of patients are stone-free at 12 months while 29-94% remain stone-free at 36 months. We propose counselling these patients on imaging versus discharge after the first year. The stone-free rate in high-risk patients not receiving targeted medical therapy is < 40% at 36 months, a fact that supports imaging, metabolic, and treatment monitoring follow-up once a year. Patients with residual fragments ≤ 4 mm have a spontaneous expulsion rate of 18-47% and a growth rate of 10-41% at 12 months, supporting annual imaging follow-up. Patients with residual fragments > 4 mm should be considered for surgical re-intervention based on the low spontaneous expulsion rate (13% at 1 year) and high risk of recurrence. Plain film KUB and/or kidney ultrasonography based on clinicians' preference and stone characteristics is the preferred imaging follow-up. Computed tomography should be considered if patient is symptomatic or intervention is planned. CONCLUSIONS: Based on evidence from the systematic review we propose, for the first time, a follow-up algorithm for patients after surgical stone treatment balancing the risks of stone recurrence against the burden of radiation from imaging studies.

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.

Consultation on UTUC II Stockholm 2022: diagnostic and prognostic methods-what's around the corner?

PURPOSE: To map current literature and provide an overview of upcoming future diagnostic and prognostic methods for upper tract urothelial carcinoma (UTUC), including translational medical science. METHODS: A scoping review approach was applied to search the literature. Based on the published literature, and the experts own experience and opinions consensus was reached through discussions at the meeting Consultation on UTUC II in Stockholm, September 2022. RESULTS: The gene mutational profile of UTUC correlates with stage, grade, prognosis, and response to different therapeutic strategies. Analysis of pathway proteins downstream of known pathogenic mutations might be an alternative approach. Liquid biopsies of cell-free DNA may detect UTUC with a higher sensitivity and specificity than urinary cytology. Extracellular vesicles from tumour cells can be detected in urine and may be used to identify the location of the urothelial carcinoma in the urinary tract. 3D microscopy of UTUC samples may add information in the analysis of tumour stage. Chemokines and chemokine receptors were linked to overall survival and responsiveness to neoadjuvant chemotherapy in muscle-invasive bladder cancer, which is potentially also of interest in UTUC. CONCLUSION: Current diagnostic methods for UTUC have shortcomings, especially concerning prognostication, which is important for personalized treatment decisions. There are several upcoming methods that may be of interest for UTUC. Most have been studied for urothelial carcinoma of the bladder, and it is important to keep in mind that UTUC is a different entity and not all methods are adaptable or applicable to UTUC.

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: 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.

Cost analysis of ureteroscopy (URS) vs extracorporeal shockwave lithotripsy (ESWL) in the management of ureteric stones <10 mm in adults: a UK perspective.

OBJECTIVES: To compare the total cost of a treatment strategy starting with ureteroscopy (URS) vs a strategy starting with extracorporeal shockwave lithotripsy (ESWL). METHODS: For ureteric stones of <10 mm, URS or ESWL are the main treatment options that are considered. Although the interventions differ, the goal of the interventions is to achieve a stone-free status. A systematic review and meta-analysis undertaken as part of the National Institute for Health and Care Excellence (NICE) guideline on 'Renal and ureteric stones: assessment and management' identified URS as more effective, in terms of getting people stone free, but has a higher probability of re-admission and adverse events (AEs) that contributes to downstream resource use. ESWL is initially less costly, but lower effectiveness means a greater need for repeat or ancillary procedures in order to get a patient stone free. Given these trade-offs between benefits and costs, a cost analysis of URS and ESWL was undertaken as part of the NICE guideline, using evidence from the literature of effectiveness, re-admission and AEs. The NICE guideline meta-analysis showed a lot of heterogeneity and differences in how outcomes were reported between studies. The costing analysis, therefore only used studies where: (i) patients were rendered stone free, and (ii) where effectiveness, was based on the first-line (initial) procedures. Exploratory quality adjusted life year (QALY) work was also undertaken to identify the QALY and quality of life (QoL) differences required for the most expensive intervention to be cost effective, based on the assumption that the difference in effectiveness between the initial procedures would be the main source of the QALY gain between the two strategies. RESULTS: The URS strategy was more costly overall than the ESWL strategy (incremental cost of £2387 [pounds sterling]). Sensitivity analysis varying the initial effectiveness of ESWL treatment (between the base case value of 82% and 40%) showed that URS would still be a more costly strategy even if the initial session of ESWL only had a success probability of 40%. A two-way sensitivity analysis as part of the exploratory QALY work showed that ESWL would have to have very low effectiveness and people would have to wait for further treatment for many weeks (following a failed ESWL treatment) for there to be feasible QoL gains to justify the additional cost of the URS strategy. CONCLUSIONS: ESWL is less effective at initial stone clearance and therefore requires more ancillary interventions than URS. However, the magnitude of the difference in costs means URS is unlikely to be cost effective intervention at a population level for first-line treatment, implying ESWL should be the first choice treatment.

Surgery for high-risk locally advanced (pT3c) renal tumours: oncological outcomes and prognostic significance of a modified International Metastatic Renal Cell Cancer Database Consortium (IMDC) score.

OBJECTIVES: To evaluate contemporary oncological outcomes and long-term survival in patients undergoing surgery for urological tumours involving the peridiaphragmatic inferior vena cava up to the level of the right atrium. To apply prognostic factors developed for metastatic renal cancer to patients with very-high-risk but apparently localized tumours, and develop a scoring system. PATIENTS AND METHODS: A retrospective cohort study of 54 patients referred between December 2007 and April 2018 to a single surgical and oncological team was conducted. Electronic patient records were used to obtain peri-operative data and oncological follow-up. For operated patients lost to follow-up, survival data were obtained from primary care physicians. We used Kaplan-Meier curves to estimate overall survival (OS) and disease-free survival. For the subgroup undergoing curative surgery (n = 32) the prognostic value of a renal cancer score developed at Guy's Hospital using five of the six criteria in the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model (one point for each of anaemia, neutrophilia, thrombophilia, hypercalcaemia and Karnofsky performance status <80), in order to be relevant for M0 disease, was assessed using the log-rank test. RESULTS: The median (interquartile range [IQR]) OS of the whole cohort was 29 (11-57) months. The median (IQR) survival of the curative subgroup (n = 32) was 32 (16-57) months, vs 11 (4-upper limit not reached) months for the cytoreductive subgroup (n = 13; P = 0.14). The median (IQR) follow-up time was 14 (1-65) months for patients alive at analysis. Disease-free survival in the curative subgroup was 10 (6-30) months. The median (IQR) OS by risk category for curative cases, as defined by the Guy's renal cancer score, was not reached in the favourable risk group (score = 0 points) because there were no patient deaths, 43 (30-61) months in the intermediate-risk group (score = 1 point), and 18 months (11-32) months in the poor-risk group (score ≥ 2 points; P = 0.005). CONCLUSION: A median survival of 29 months appears to justify this type of surgery. A prognostic model, the Guy's renal cancer score, using five readily available clinical measures, appears promising in patients with very-high-risk locally advanced tumours.

Associating mutations causing cystinuria with disease severity with the aim of providing precision medicine.

BACKGROUND: Cystinuria is an inherited disease that results in the formation of cystine stones in the kidney, which can have serious health complications. Two genes (SLC7A9 and SLC3A1) that form an amino acid transporter are known to be responsible for the disease. Variants that cause the disease disrupt amino acid transport across the cell membrane, leading to the build-up of relatively insoluble cystine, resulting in formation of stones. Assessing the effects of each mutation is critical in order to provide tailored treatment options for patients. We used various computational methods to assess the effects of cystinuria associated mutations, utilising information on protein function, evolutionary conservation and natural population variation of the two genes. We also analysed the ability of some methods to predict the phenotypes of individuals with cystinuria, based on their genotypes, and compared this to clinical data. RESULTS: Using a literature search, we collated a set of 94 SLC3A1 and 58 SLC7A9 point mutations known to be associated with cystinuria. There are differences in sequence location, evolutionary conservation, allele frequency, and predicted effect on protein function between these mutations and other genetic variants of the same genes that occur in a large population. Structural analysis considered how these mutations might lead to cystinuria. For SLC7A9, many mutations swap hydrophobic amino acids for charged amino acids or vice versa, while others affect known functional sites. For SLC3A1, functional information is currently insufficient to make confident predictions but mutations often result in the loss of hydrogen bonds and largely appear to affect protein stability. Finally, we showed that computational predictions of mutation severity were significantly correlated with the disease phenotypes of patients from a clinical study, despite different methods disagreeing for some of their predictions. CONCLUSIONS: The results of this study are promising and highlight the areas of research which must now be pursued to better understand how mutations in SLC3A1 and SLC7A9 cause cystinuria. The application of our approach to a larger data set is essential, but we have shown that computational methods could play an important role in designing more effective personalised treatment options for patients with cystinuria.

Raised preoperative international normalised ratio (INR) identifies patients at high risk of perioperative death after simultaneous renal and cardiac surgery for tumours involving the peri-diaphragmatic inferior vena cava and right atrium.

OBJECTIVE: To identify preoperative factors that predict 30-day mortality in patients undergoing simultaneous cardiac and renal surgery for urological tumours involving the peri-diaphragmatic vena cava and right atrium- The ability to predict mortality and therefore avoid surgery in those patients likely to die would be valuable. PATIENTS AND METHODS: We retrospectively reviewed perioperative outcomes in patients managed between December 2007 and January 2016 by a single team. The relationships of outcome measurements were analysed using Fisher's exact and Mann-Whitney U-tests. RESULTS: Of the 46 patients identified, 41 (89%) underwent surgery (20 males and 21 females). The median (range) age was 65 (17-95) years. Histology confirmed 37 renal cell cancers, one adrenal cancer, two primitive neuroectodermal tumours, and one leiomyosarcoma. The overall 30-day mortality rate was 7% (three of 41 patients). The international normalised ratio (INR), age, and estimated glomerular filtration rate (eGFR) correlated significantly with 30-day mortality. The mortality rate was high in patients with an INR ≥1.5 and <1.5 (with three of the five patients dying) compared to those with an INR <1.5 (0/36 patients died; 30 day mortality 0%). The INR correlated with serious complications (≥Clavien-Dindo Grade III), which occurred in all five patients with an INR ≥1.5 and <1.5 vs 12/36 (33%) with an INR <1.5 (P < 0.002). The median (range) eGFR in those that died was 36 (26-37) mL/min/1.73 m2 compared to 52 (24-154) mL/min/1.73 m2 in those that survived (P = 0.018). CONCLUSIONS: In patients undergoing combined cardiac and renal tumour surgery raised preoperative INR is associated with a high risk of 30-day mortality when the patient is elderly (>70 years) and of significant post-operative complications in younger patients (<70 years). Surgery in patients with a normal INR is challenging but much safer.

What is the quickest scoring system to predict percutaneous nephrolithotomy outcomes? A comparative study among S.T.O.N.E score, guy's stone score and croes nomogram.

OBJECTIVE: To compare the application time and the capacity of the nomograms to predict the success of Guy's Stone Score (GSS), S.T.O.N.E. Nephrolithometry (STONE) and Clinical Research Office of the Endourological Society nephrolithometric nomogram (CROES) of percutaneous nephrolithotomy (PCNL), evaluating the most efficient one for clinical use. MATERIALS AND METHODS: We studied 48 patients who underwent PCNL by the same surgeon between 2010 and 2011. We calculated GSS, STONE and CROES based on preoperative non-contrast computed tomography (CT) images and clinical data. A single observer, blinded to the outcomes, reviewed all images and assigned scores. We compared the application time of each nomogram. We used an analysis of variance for repeated measures and multiple comparisons by the Tukey test. We compared the area under the ROC curve (AUC) of the three nomograms two by two to determine the most predictive scoring system. RESULTS: The immediate success rate was 66.7% and complications occurred in 16.7% of cases. The average operative time was 122 minutes. Mean application time was significantly lower for the GSS (27.5 seconds) when compared to 300.6 seconds for STONE and 213.4 seconds for CROES (p<0.001). There was no significant difference among the GSS (AUC=0.653), STONE (AUC=0.563) and CROES (AUC=0.641) in the ability to predict immediate success of PCNL. CONCLUSIONS: All three nomograms showed similar ability to predict success of PCNL, however the GSS was the quickest to be applied, what is an important issue for routine clinical use when counseling patients who are candidates to PCNL.

Sequential bacillus Calmette-Guérin/Electromotive Drug Administration of Mitomycin C as the Standard Intravesical Regimen in High Risk Nonmuscle Invasive Bladder Cancer: 2-Year Outcomes.

PURPOSE: Sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C is reported to be superior to bacillus Calmette-Guérin alone but it has not been widely adopted. We aimed to determine the efficacy and tolerability of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in high risk, nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Starting in 2009 bacillus Calmette-Guérin/electromotive drug administration of mitomycin C was introduced as the standard induction regime in patients with high risk, nonmuscle invasive bladder cancer undergoing bladder conservation. As induction bacillus Calmette-Guérin was administered in weeks 1 and 2. Mitomycin C was administered in electromotive fashion (40 mg and 20 mA current for 30 minutes) in week 3 and repeated thrice for a total of 9 weeks. As maintenance 3 doses of bacillus Calmette-Guérin were given 3 months after induction and then every 6 months for 3 years. Outcome measures were disease recurrence at first check, 1 and 2-year cystoscopy, and treatment tolerability. RESULTS: Of the 151 patients with high risk, nonmuscle invasive bladder cancer treated between June 2009 and 2013, 44 underwent primary cystectomy and 107 received sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C. Disease was high grade Ta/T1 in 86 patients (80%), of whom 34 (32%) also had carcinoma in situ. A total of 19 patients (18%) had primary carcinoma in situ and 2 had recurrent large volume, low grade disease. Of 107 patients 104 underwent first check cystoscopy, including 90 (87%) who were clear. Of the 90 complete responders 86 underwent 1-year cystoscopy, including 74 (86%) who were recurrence-free. Of the 74 patients 71 underwent 2-year cystoscopy, of whom 66 (93%) remained recurrence-free. The full induction schedule was not completed in 30 patients (28%), including 16 and 14 with minor and major schedule alterations, respectively. There was no difference in recurrence between patients who received a full vs a reduced induction schedule. CONCLUSIONS: This study confirms the excellent oncologic efficacy of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in cases of high risk, nonmuscle invasive bladder cancer. Tolerability is a challenge but alterations to the 9-week schedule appeared to have a negligible impact on outcomes.

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.

Control of hair growth using long-pulsed alexandrite laser is an efficient and cost effective therapy for patients suffering from recurrent pilonidal disease.

Pilonidal sinus (PNS) and its surgical management have a profound impact on hospital resources in terms of finances and productive man-hours. Surgical treatment has been the mainstay of treatment of both acute and chronic pilonidal sinus but recurrence is common. The control of hair growth in the sinus region plays an important role in preventing recurrence. Here, we discuss our experience of treating 19 patients suffering from recurrent pilonidal sinus with laser depilation and its long-term cost effectiveness. This is a retrospective study on patients who had recurrence of pilonidal sinus following multiple surgical treatments. They were treated using long-pulsed alexandrite laser for depilation in the sinus area, an outpatient procedure. Their clinical characteristics and outcomes were then evaluated. There was a significant reduction in hair density after laser treatment (p < 0.001). The disease-free period after laser treatment was significantly longer than that one after surgical treatment (p < 0.001). The average cost of repeated surgical treatment per disease-free month was significantly higher than that of laser treatment (p < 0.001). Evidence suggests the role of natal cleft hair growth in the evolution of the pilonidal disease; therefore, control of hair growth should be considered as an adjunct to the initial treatment via surgery. Compared to surgical treatment of recurrences, laser depilation is an efficient and cost-effective method of preventing recurrence and reducing morbidity and loss of man-hours. We suggest that laser depilation of the pilonidal sinus should be funded by clinical commissioning groups.