Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Urolithiasis is a major clinical and economic burden for health care systems. International epidemiological data suggest that the incidence and prevalence of stone disease is increasing. This study demonstrates that the number of diagnoses and procedures relating to kidney stone disease has increased significantly in the last 10 years in the UK. Management of stone disease comprises a significant and increasing proportion of urological practice in the UK, which has implications for work force planning, training, service delivery and research in this field. OBJECTIVE To summarize the changes in prevalence and treatment of upper urinary tract stone disease in the UK over the last 10 years. METHODS Data from the Hospital Episode Statistics (HES) website (http://www.hesonline.nhs.uk) were extracted, summarized and presented. RESULTS The number of upper urinary tract stone hospital episodes increased by 63% to 83 050 in the 10‐year period. The use of shock wave lithotripsy (SWL) for treating all upper tract stones increased from 14 491 cases in 2000–2001 to 22 402 cases in 2010 (a 55% increase) with a 69% increase in lithotripsy for renal stones. There was a 127% increase in the number of ureteroscopic stone treatments from 6 283 to 14 242 cases over the 10‐year period with a 49% increase from 2007/2008 to 2009/2010. There was a decline in open surgery for upper tract stones from 278 cases in 2000/2001 to 47 cases in 2009/2010 (an 83% reduction). Treatment for stone disease has increased substantially in comparison with other urological activity. In 2009/2010, SWL was performed almost as frequently as transurethral resection of the prostate or transurethral resection of bladder tumour, ureteroscopy for stones was performed more frequently than nephrectomy, radical prostatectomy and cystectomy combined, and percutaneous nephrolithotomy was performed more frequently than cystectomy. CONCLUSIONS The present study highlights the increase in prevalence and treatment of stone disease in the UK over the last 10 years. If this trend continues it has important implications for workforce planning, training, service delivery and research in the field of urolithiasis.

What ' s known on the subject? and What does the study add?Haematuria clinics with same day imaging and fl exible cystoscopy are an effi cient way for investigating patients with haematuria. The principal role of haematuria clinics with reference to bladder cancer is to determine which patients are ' normal ' and may be discharged, and which patients are abnormal and should undergo rigid cystoscopy. It is well recognised that CT urography offers a thorough evaluation of the upper urinary tract for stones, renal masses and urothelial neoplasms but the role of CT urography for diagnosing bladder cancer is less certain. The aim of the present study was to evaluate the diagnostic accuracy of CT urography in patients with visible haematuria aged > 40 years and to determine if CT urography has a role for diagnosing bladder cancer.This study shows that the optimum diagnostic strategy for investigating patients with visible haematuria aged > 40 years with infection excluded is a combined strategy using CT urography and fl exible cystoscopy. Patients positive for bladder cancer on CT urography should be referred directly for rigid cystoscopy and so avoid fl exible cystoscopy. The number of fl exible cystoscopies required therefore may be reduced by 17%. The present study also shows that the diagnostic accuracy of voided urine cytology is too low to justify its continuing use in a haematuria clinic using CT urography and fl exible cystoscopy. OBJECTIVES• To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with fl exible cystoscopy and voided urine cytology for diagnosing bladder cancer.• To evaluate diagnostic strategies using CT urography as: (i) an additional test or (ii) a replacement test or (iii) a triage test for diagnosing bladder cancer in patients referred to a hospital haematuria rapid diagnosis clinic. PATIENTS AND METHODS• The clinical cohort consisted of a consecutive series of 778 patients referred to a hospital haematuria rapid diagnosis clinic from 1 March 2004 to 17 December 2007. Criteria for referral were at least one episode of macroscopic haematuria, age > 40 years and urinary tract infection excluded. Of the 778 patients, there were 747 with technically adequate CT urography and fl exible cystoscopy examinations for analysis.• On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and fl exible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and fl exible cystoscopy performed by a urologist. Both examinations were scored using a 3-point system: 1, normal; 2, equivocal; and 3, positive for bladder cancer.• The reference standard consisted of review of the hospital imaging and histopathology databases in December 2009 for all patients and reports from the medical notes for those referred for rigid cystoscopy. Follow-up was for 21 -66 months. RESULTS• The prevalence of bladder cancer in the clinical cohort was 20% (156/77...

This study provides an update on the changing landscape of the management of UUT stones in England. It shows a sustained high prevalence of stone disease commensurate with levels in other developed countries. This study reveals a trend in the last 5 years to surgically intervene on a higher proportion of patients with stones. As in other countries, there is a significant increase in the use of ureteroscopy (particularly intrarenal flexible ureteroscopy) in England. These data have important implications for work-force planning, training, service delivery, and research in the field of urolithiasis.

Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45–60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.

We have developed an automated, highly sensitive and specific method for identifying and enumerating circulating tumour cells (CTCs) in the blood. Blood samples from 10 prostate, 25 colorectal and 4 ovarian cancer patients were analysed. Eleven healthy donors and seven men with elevated serum prostate-specific antigen (PSA) levels but no evidence of malignancy served as controls. Spiking experiments with cancer cell lines were performed to estimate recovery yield. Isolation was performed either by density gradient centrifugation or by filtration, and the CTCs were labelled with monoclonal antibodies against cytokeratins 7/8 and either AUA1 (against EpCam) or anti-PSA. The slides were analysed with the Ikoniscope s robotic fluorescence microscope imaging system. Spiking experiments showed that less than one epithelial cell per millilitre of blood could be detected, and that fluorescence in situ hybridisation (FISH) could identify chromosomal abnormalities in these cells. No positive cells were detected in the 11 healthy control samples. Circulating tumour cells were detected in 23 out of 25 colorectal, 10 out of 10 prostate and 4 out of 4 ovarian cancer patients. Five samples (three colorectal and two ovarian) were analysed by FISH for chromosomes 7 and 8 combined and all had significantly more than four dots per cell. We have demonstrated an Ikoniscope s based relatively simple and rapid procedure for the clear-cut identification of CTCs. The method has considerable promise for screening, early detection of recurrence and evaluation of treatment response for a wide variety of carcinomas.

The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.

RESULTSThe prevalence of bladder tumours was 24%; when CTU was compared with the histopathological findings, there was one false-positive and three false-negative diagnoses, indicating a sensitivity of 0.93 and a specificity of 0.99, with a 0.98 positive and 0.97 negative predictive value for detecting bladder cancer. A review of the three falsenegative cases showed that one was missed on original CTU reporting, the second had the appearance of prostate cancer on CTU and the third was a squamous metaplasia. CONCLUSIONSCTU is an accurate method of detecting bladder tumours in the present patients, and is reliable and accurate for assessing the bladder. Our results support the use of CTU as a first-line screening tool for this high-risk group, the use of which will obviate the need for flexible cystoscopy in patients with a negative CTU and allow those with an obvious tumour to be referred directly for rigid cystoscopy and resection. The remaining patients should be referred for flexible cystoscopy. Such a pathway would accelerate patient assessment by using fewer tests and provide a true 'one-stop' clinic, allowing a comprehensive evaluation with a single test for the upper and lower urinary tract. KEYWORDS macroscopic haematuria, haematuria, bladder cancer, cystoscopy, virtual cystoscopy, CT urography OBJECTIVETo evaluate the use of computed tomography urography (CTU) for diagnosing bladder tumours in patients with macroscopic haematuria and aged > 40 years. PATIENTS AND METHODSIn all, 200 consecutive patients attending a fast-track haematuria clinic were assessed using 'same-day' CTU and flexible cystoscopy. Patients were aged > 40 years and had macroscopic haematuria with no urine infection. CTU studies were reported by one uroradiologist and scored on a 3-point scale to quantify the probability of bladder cancer. All flexible cystoscopies were performed by the same cystoscopist with no knowledge of the findings of CTU, and scored using a 3-point scale. Cystoscopy, pathological findings and CTU were then compared.

These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.