An analysis of stone management over the decade before the COVID-19 pandemic in Germany, France and England.

OBJECTIVES: To understand the implications that the rising upper urinary tract (UUT) stone prevalence in Europe and the increasing burden places on patients and healthcare providers (HCPs), we investigated the evolution of diagnoses and procedures in Germany, France and England over the decade before the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We identified International Classification of Diseases (ICD)-10 codes related to UUT stones diagnosis and extracted procedure volumes for extracorporeal shockwave lithotripsy (ESWL), ureteroscopy (URS), percutaneous nephrolithotomy and open surgery using national procedure codes from the German Institute for the Hospital Remuneration System, the French Technical Agency of Hospitalisation Information and NHS England Hospital Episode Statistics. We analysed procedures vs hospital diagnoses from 2010 to 2019 and reported results per 100 000 inhabitants. RESULTS: Between 2010 and 2019, ICD-10 N20 codes for calculus of kidney and ureter increased by 8%, 26% and 15% in Germany, France, and England respectively; whereas procedures increased by 3%, 38% and 18%. Of the patients diagnosed with stones, the percentage that received treatment (of any type) differed between countries. In 2019, in Germany 83% of patients diagnosed with stones received treatment, in France 88%, and in England 56%. These figures were relatively stable over the 10-year study period. Over the past decade, the dominant procedure shifted from ESWL to URS, and the average length of stay for URS decreased. Day case procedures increased in France and England (by 68% and 23%), no data were available in Germany. CONCLUSION: This analysis highlights an increase in stone diagnoses and procedures, and a shift of surgical management. This development may be due to clinical advantages and advanced technology. The continued stone prevalence rise affects patients, hospitals, and HCPs.

The New Lithotripsy Index predicts success of shock wave lithotripsy.

AIM: The aim of this study is to evaluate the factors affecting treatment success in patients who underwent Shock wave lithotripsy (SWL) and to investigate the effect of the Storz Medical Lithotripsy Index (SMLI) on treatment effectiveness. METHODS: Prospective data were collected on patients undergoing SWL treatment for kidney stones between January 2013 and May 2021. Stone location, number and size were determined with non-contrast CT (NCCT) for all patients. All patients underwent SWL with a Storz Modulith SLK lithotripsy machine without anaesthesia. The total amount of energy applied to the stone was calculated using the SMLI. All patients were evaluated for stone-free status by X-ray at least 2 weeks after treatment. The success of the procedure was defined as the patient being completely stone free or the detection of residual fragments < 4 mm that did not require further treatment. RESULTS: A total of 1230 patients with kidney stones were included in the study. The mean age of the patients was 42.33 ± 11.78 (18-75), and the mean BMI was 28.47 ± 8.78 (19.25-38.52). During SWL, 75.6% of patients demonstrated excellent pain tolerance (930/1230). A total of 116 patients could not tolerate the pain during SWL (9.4%). Treatment success was associated with fewer treatment sessions (2.34 ± 1.75 vs. 2.90 ± 2.04; p < 0.001), smaller stone size (7.52 ± 3.29 vs 8.60 ± 3.93; p < 0.001) and higher SMLI/stone size (25.11 ± 13.63 vs. 22.27 ± 14.50; p < 0.001). In the univariate and multivariate regression analysis, the factors affecting the success of the treatment were the number of sessions (OR 1.170), stone size (OR 1.142), number of shocks (OR 1.005), SMLI/stone size (OR 1.024) and pain tolerance (OR 0.692). CONCLUSION: In the treatment of kidney stones with SWL, stone site, stone size, SMLI/stone size, and pain tolerance are the factors affecting success. SMLI per stone size is a statistically significant factor for predicting SWL success.

Utility of blood tests in screening for metabolic disorders in kidney stone disease.

OBJECTIVES: To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease. SUBJECTS AND METHODS: Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney stones were prospectively collected between April 2011 and February 2017. Data were analysed to determine the utility of serum calcium, parathyroid hormone (PTH), urate, chloride, bicarbonate, potassium and phosphate assays in screening for primary hyperparathyroidism, normocalcaemic hyperparathyroidism, hyperuricosuria, distal renal tubular acidosis (dRTA) and hypercalciuria. RESULTS: An elevated serum calcium level was detected in 2.3% of patients. Further investigations prompted by this finding resulted in a diagnosis of primary hyperparathyroidism in 0.2% of men and 4.6% of women for whom serum calcium was recorded. An elevated serum PTH level in the absence of hypercalcaemia was detected in 15.1% of patients. Of these patients, 74.6% were vitamin D-insufficient; no patients were diagnosed with normocalcaemic hyperparathyroidism. Hyperuricosuria was present in 21.6% of patients and hypercalciuria in 47.1%. Hyperuricaemia was not associated with hyperuricosuria, nor was hypophosphataemia associated with hypercalciuria. No patient was highlighted as being at risk of dRTA using serum chloride and bicarbonate as screening tests. CONCLUSION: This study indicates that individuals presenting with renal calculi should undergo metabolic screening with a serum calcium measurement alone. Use of additional blood tests to screen for metabolic disorders is not cost-effective and may provide false reassurance that metabolic abnormalities are not present. A full metabolic assessment with 24-h urine collection should be undertaken in recurrent stone formers and in those at high risk of future stone disease to identify potentially treatable metabolic abnormalities.

A Drosophila genetic model of nephrolithiasis: transcriptional changes in response to diet induced stone formation.

BACKGROUND: Urolithiasis is a significant healthcare issue but the pathophysiology of stone disease remains poorly understood. Drosophila Malpighian tubules were known to share similar physiological function to human renal tubules. We have used Drosophila as a genetic model to study the transcriptional response to stone formation secondary to dietary manipulation. METHODS: Wild-type male flies were raised on standard medium supplemented with lithogenic agents: control, sodium oxalate (NaOx) and ethylene glycol (EG). At 2 weeks, Malpighian tubules were dissected under polarized microscope to visualize crystals. The parallel group was dissected for RNA extraction and subsequent next-generation RNA sequencing. RESULTS: Crystal formation was visualized in 20%(±2.2) of flies on control diet, 73%(±3.6) on NaOx diet and 84%(±2.2) on EG diet. Differentially expressed genes were identified in flies fed with NaOx and EG diet comparing with the control group. Fifty-eight genes were differentially expressed (FDR <0.05, p < 0.05) in NaOx diet and 20 genes in EG diet. The molecular function of differentially expressed genes were assessed. Among these, Nervana 3, Eaat1 (Excitatory amino acid transporter 1), CG7912, CG5404, CG3036 worked as ion transmembrane transporters, which were possibly involved in stone pathogenesis. CONCLUSIONS: We have shown that by dietary modification, stone formation can be manipulated and visualized in Drosophila Malpighian tubules. This genetic model could be potentially used to identify the candidate genes that influence stone risk hence providing more insight to the pathogenesis of human stone disease.

The Preoperative Assessment and Optimization of Patients Undergoing Major Urological Surgery.

PURPOSE OF REVIEW: Improving patient outcomes from major urological surgery requires not only advancement in surgical technique and technology, but also the practice of patient-centered, multidisciplinary, and integrated medical care of these patients from the moment of contemplation of surgery until full recovery. This review examines the evidence for recent developments in preoperative assessment and optimization that is of relevance to major urological surgery. RECENT FINDINGS: Current perioperative medicine recommendations aim to improve the short-term safety and long-term effectiveness of surgical treatments by the delivery of multidisciplinary integrated medical care. New strategies to deliver this aim include preoperative risk stratification using a frailty index and cardiopulmonary exercise testing for patients undergoing intra-abdominal surgery (including radical cystectomy), preoperative management of iron deficiency and anemia, and preoperative exercise intervention. Proof of the utility and validity for improving surgical outcomes through advances in preoperative care is still evolving. Evidence-based developments in this field are likely to benefit patients undergoing major urological surgery, but further research targeted at high-risk patients undergoing specific urological operations is required.

Management of iatrogenic ureteric injury with retrograde ureteric stenting: an analysis of factors affecting technical success and long-term outcome.

Background Iatrogenic ureteral injuries arise as serious complication following obstetrics, gynecological, general, and urological surgery with incidence in the range of 0.5-10%. Retrograde placement of double-J ureteric stent is a possible treatment option if the injury is not recognized at the time of surgery. Purpose To assess technical success and long-term outcome associated with retrograde ureteric stent insertion for iatrogenic ureteric injury. Material and Methods Between 1999 and 2011, 26 patients with initially unrecognized iatrogenic ureteric injury underwent initial management with retrograde ureteric stenting. Full case-notes were available for review in 25 patients. Results The mean interval from injury to attempted stenting was 19.4 days. Successful retrograde ureteric stenting was achieved in 21/25 patients (81%). Retrograde stenting failed in four patients, and nephrostomy followed by alternative procedures were performed instead. At a median follow-up interval of 9.7 months, normal anatomy was demonstrated on 12/21 patients (57%) and a stricture was observed in 6/21 patients (28%) with three requiring surgical intervention. Conclusion Retrograde stenting is a safe and efficient initial management in patients with iatrogenic ureteric injuries.

Tracking kidney stones in a homogeneous medium using a trilateration approach.

Shock wave lithotripsy is a non-invasive procedure by which kidney stones are fragmented by thousands of shock waves. Currently, many shock waves are delivered to the body that do not impact the stone, but do result in tissue trauma. This motivates developing a monitoring system to locate kidney stones, with the goal of gating shock waves not aligned with the stone, and hence, reducing renal trauma during lithotripsy. The system consists of a circular array housing twenty-two 0.5 MHz transducers that can be mounted on a clinical lithotripter. It was deployed in a water tank and tested with two stone models made from gypsum cement and a stone model fragment. An algorithm consisting of threshold detection, automatic rejection of weak signals, and triangulation was developed to determine the location of stones. The results show that within ±15 mm of the focus of the lithotripter, the accuracy was better than 4 mm in the lateral directions and 2 mm in the axial direction. Using off-the-shelf hardware, the algorithm can calculate stone positions every 1 s allowing for real-time tracking during lithotripsy.

Trends in urological stone disease: a 5-year update of hospital episode statistics.

OBJECTIVE: To provide a 5-year follow-on update on the changes in prevalence and treatment of upper urinary tract (UUT) stone disease in England. METHODS: Data from the Hospital Episode Statistics (HES) website (http://www.hesonline.nhs.uk) were extracted, summarised, analysed, and presented. RESULTS: The total number of UUT stone hospital episodes increased slightly from 83 050 in 2009-2010 to 86 742 in 2014-2015 (4.4% increase). The use of shockwave lithotripsy (SWL) for treating all UUT stones remained stable over the 5-year study period following a significant increase in previous years. There was a 49.6% increase in the number of ureteroscopic stone treatments from 12 062 in 2009-2010 to 18 055 in 2014-2015. Increase in ureterorenoscopy (flexible ureteroscopy) showed the most rapid increase from 3 267 to 6 631 cases in the 5-year study period (103% increase). The gap between the total number of ureteroscopies and SWL treatments continues to narrow. Open stone surgery continued to decline with only 30 reported cases in 2014-2015. Due to the continued rapid increase in the number of ureteroscopies performed, treatment for stone disease has continued to increase significantly in comparison to other urological activity. CONCLUSION: 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.

Shock wave lithotripsy (SWL): outcomes from a national SWL database in New Zealand.

OBJECTIVES: To present the national outcomes for New Zealand of over 9000 stone cases treated with SWL at 21 centres over a 20 year period. SUBJECTS/PATIENTS AND METHODS: Stone cases treated with SWL on board the Mobile Medical Technology (MMT) vehicle between 19 June 1995 and 1 December 2014 were identified, and data collection undertaken prospectively for patient, stone and treatment characteristics, and retrospectively for treatment outcomes. The primary outcome was treatment success, defined as complete stone clearance or clinically insignificant residual fragments (CIRFs) of ≤4 mm. Secondary outcomes were stone free rate, complications and auxiliary procedures, and all statistical analyses were descriptive. RESULTS: 9538 stone cases (7769 patients) were included. The overall, cumulative success rate was 58.7%; this included 45.1% that were stone free and 13.5% in which there were CIRFs ≤4 mm. Success rates varied widely by stone size and location. Overall rates of urinary tract infection, perinephric haematoma, hospital admission and ureteral stent placement were 1.1%, 0.2%, 6.8% and 4.1%, respectively. Variations in SWL protocols across centres limits the overall reliability of our findings. CONCLUSION: SWL remains a low morbidity management option requiring careful patient selection. This study provides valuable data for patient counseling and the formation of evidence based guidelines in SWL. The MMT SWL service has demonstrated that is it possible to deliver a high volume specialist stone service without requiring patients to travel further for treatment.

Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).

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.

Switching off micturition using deep brain stimulation at midbrain sites.

Most of the time the bladder is locked in storage mode, switching to voiding only when it is judged safe and/or socially appropriate to urinate. Here we show, in humans and rodents, that deep brain stimulation in the periaqueductal gray matter can rapidly and reversibly manipulate switching within the micturition control circuitry, to defer voiding and maintain urinary continence, even when the bladder is full. Manipulation of neural continence pathways by deep brain stimulation may offer new avenues for the treatment of urinary incontinence of central origin.

Storz Medical Lithotripsy Index Predicts Success of Shock Wave Lithotripsy in Ureteric Stones.

PURPOSE: The aim of this study is to evaluate the factors affecting treatment success in patients who underwent Shock wave lithotripsy (SWL) for ureter stones and to investigate the effect of Storz Medical Lithotripsy Index (SMLI) on treatment effectiveness in ureteric stones. METHOD: Prospective data were collected on patients undergoing SWL treatment for ureter stones between January 2013 and May 2021. Stone location, number, and size were determined with Non contrast CT (NCCT) for all patients. All patients underwent SWL with a Storz Modulith SLK lithotripsy machine with local anaesthesia. The total amount of energy applied to the stone was calculated using the Storz Medical Lithotripsy Index (SMLI). All patients were evaluated for stone-free status by X-ray at least 2 weeks after treatment. The success of the procedure was defined as the patient being completely stone free (SF) or detection of residual fragments < 4 mm that did not require further treatment Results: A total of 1199 patients with ureter stones were included in the study. The mean age of the patients was 43.11 ± 10.65 (18-73), and the mean BMI was 27.87±8.12(19.02-38.65). During SWL, 89.3% of patients demonstrated excellent pain tolerance (1070/1199). A total of 119 patients could not tolerate pain during SWL (10.7%). Treatment success was associated with fewer treatment sessions (2.04±1.64 vs. 2.50 ± 1.48; p < 0.001), smaller stone size (7.35±2.99 vs. 9.02 ± 3.81; p < 0.001) and higher SMLI/stone size (29.70 ± 17.48 vs. 24.98±16.01; p < 0.001). In the univariate and multivariate regression analysis, the factors affecting the success of the treatment were the number of sessions (OR: 1.147), stone size (OR: 1.112), SMLI/stone size (OR: 1.115) and pain tolerance (OR: 0.740). CONCLUSION: In the treatment of ureteral stones with SWL, number of sessions, stone size, SMLI/stone size, and pain tolerance are the factors affecting success. SMLI per stone size is a statistically significant factor for predicting SWL success.

Trends in urological stone disease.

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.

Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria clinic.

UNLABELLED: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Haematuria clinics with same day imaging and flexible cystoscopy are an efficient 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 flexible cystoscopy. Patients positive for bladder cancer on CT urography should be referred directly for rigid cystoscopy and so avoid flexible cystoscopy. The number of flexible 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 flexible cystoscopy. OBJECTIVES: To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with flexible 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 flexible cystoscopy examinations for analysis. On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and flexible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and flexible 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% (156/778). For the diagnostic strategy using CT urography as an additional test for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 1.0 (95% confidence interval [CI] 0.98-1.00), specificity was 0.94 (95% CI 0.91-0.95), the positive predictive value (PPV) was 0.80 (95% CI 0.73-0.85) and the negative predictive value (NPV) was 1.0 (95% CI 0.99-1.00). For the diagnostic strategy using CT urography as a replacement test for flexible cystoscopy for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.83 (95% CI 0.80-0.86), the PPV was 0.58 (95% CI 0.52-0.64), and the NPV was 0.98 (95% CI 0.97-0.99). Similarly using flexible cystoscopy for diagnosing bladder cancer, if scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.98 (95% CI 0.94- 0.99), specificity was 0.94 (95% CI 0.92-0.96), the PPV was 0.80 (95% CI 0.73-0.85) and the NPV was 0.99 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), patients with a positive CT urography score are referred directly for rigid cystoscopy, and patients with an equivocal or normal score were referred for flexible cystoscopy. Sensitivity was 1.0 (95% CI 0.98-1.0), specificity was 0.94 (95% CI 0.91-0.95), the PPV was 0.80 (95% CI 0.73-0.85), and the NPV was 1.0 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 2), patients with a positive CT urography score are referred directly for rigid cystoscopy, patients with an equivocal score are referred for flexible cystoscopy and patients with a normal score undergo clinical follow-up. Sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.93 (95% CI 0.87-0.96), and the NPV was 0.99 (95% CI 0.97-0.99). For voided urine cytology, if scores of 0-3 were classified as negative and 4-5 as positive for bladder cancer, sensitivity was 0.38 (95% CI 0.31-0.45), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.82 (95% CI 0.72-0.88) and the NPV was 0.84 (95% CI 0.81-0.87). CONCLUSIONS: There is a clear advantage for the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), in which patients with a positive CT urography score for bladder cancer are directly referred for rigid cystoscopy, but all other patients undergo flexible cystoscopy. Diagnostic accuracy is the same as for the additional test strategy with the advantage of a 17% reduction of the number of flexible cystoscopies performed. The sensitivity of voided urine cytology is too low to justify its continuing use in a hospital haematuria rapid diagnosis clinic using CT urography and flexible cystoscopy.

Serial analysis of resected prostate cancer suggests up-regulation of type 1 IGF receptor with disease progression.

OBJECTIVE: • To compare immunostaining protocols using different antibodies for the type 1 insulin-like growth factor receptor (IGF-1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF-1R expression varies with time in serial prostate cancer specimens from individual patients. METHODS: • We studied IGF-1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart. • Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate-specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation. • After an optimization process using three commercially-available IGF-1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips. RESULTS: • Santa Cruz antibody sc713 gave positive staining in IGF-1R null R- cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R- cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively. • There was significant correlation of IGF-1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF-1R staining scores generated by the CS antibody were used to analyze the clinical data. • Most patients (six of seven) with falling IGF-1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response) between operations. Conversely, in seven of eight patients who had progression to androgen-independence between procedures, IGF-1R levels increased or remained high. Finally, seven of 11 patients who developed radiologically confirmed metastases between procedures showed stable or increasing IGF-1R staining scores. CONCLUSION: • The present study is the first to assess changes in IGF-1R expression in serial prostate cancer samples. The results obtained indicate that IGF-1R expression usually remains high throughout the course of histologically-proven disease progression in serial specimens, suggesting that the IGF-1R remains a valid treatment target for advanced prostate cancer.

Predicting shockwave lithotripsy outcome for urolithiasis using clinical and stone computed tomography texture analysis variables.

We aimed to develop and evaluate a statistical model, which included known pre-treatment factors and new computed tomography texture analysis (CTTA) variables, for its ability to predict the likelihood of a successful outcome after extracorporeal shockwave lithotripsy (SWL) treatment for renal and ureteric stones. Up to half of patients undergoing SWL may fail treatment. Better prediction of which cases will likely succeed SWL will help patients to make an informed decision on the most effective treatment modality for their stone. 19 pre-treatment factors for SWL success, including 6 CTTA variables, were collected from 459 SWL cases at a single centre. Univariate and multivariable analyses were performed by independent statisticians to predict the probability of a stone free (both with and without residual fragments) outcome after SWL. A multivariable model had an overall accuracy of 66% on Receiver Operator Curve (ROC) analysis to predict for successful SWL outcome. The variables most frequently chosen for the model were those which represented stone size. Although previous studies have suggested SWL can be reliably predicted using pre-treatment factors and that analysis of CT stone images may improve outcome prediction, the results from this study have not produced a useful model for SWL outcome prediction.

Impact of Case Volume on Shock Wave Lithotripsy Outcomes: Data from the National Shock Wave Lithotripsy Database of New Zealand.

Purpose: To assess the impact of individual operator case volume on shock wave lithotripsy (SWL) treatment outcomes in more than 9000 stone cases over a 20-year period in New Zealand. Materials and Methods: Stone cases treated with SWL on the Mobile Medical Technology (MMT) vehicle between June 19, 1995, and December 1, 2014, were identified. Data collection was undertaken prospectively for patient, stone, and treatment characteristics, and retrospectively for treatment outcomes. Multivariate analysis using binary logistic regression was undertaken to assess whether radiographer stone case volume (stones/year) was an independent predictor of SWL success (stone free or clinically insignificant residual fragments ≤4 mm at follow-up). Results: Sixteen radiographers delivered treatment to the included cohort (9039 stone cases), with a median case volume (stones/year) of 73 (range: 37-197) and median total of 425 stones treated (range: 71-1721). The two radiographers with highest case volumes achieved the highest success rates. Radiographer case volume (stones/year) was independently associated with SWL success (odds ratio [OR]: 1.004, 95% confidence interval [CI]: 1.003-1.005, p < 0.0001) and reduced need for post-SWL hospital admission (OR: 0.997, 95% CI: 0.994-1.000, p = 0.028), but there was no associated decrease in post-SWL urosepsis (OR: 0.999, 95% CI: 0.974-1.025, p = 0.941), perinephric hematoma (OR: 1.003, 95% CI: 0.985-1.020, p = 0.778), or need for auxiliary procedures (OR: 1.000, 95% CI: 0.998-1.002, p = 0.871). Conclusions: SWL success rates can be improved by increasing the frequency of cases performed by individual operators. In this multicenter cohort of more than 9000 stone cases treated over a 20-year period, the best outcomes were seen for those radiographers performing >150 cases per year.

The Fluid Mechanics of Ureteroscope Irrigation.

PURPOSE: To develop a physical understanding of ureterorenoscopy irrigation, we derive mathematical models from basic physical principles and compare these predictions with the results of benchtop experiments. Mathematical modeling can be used to understand the role of inlet pressure, tip deflection, the presence of working tools, geometric properties of the instruments used, and material properties of the irrigation fluid on resulting flow rate. MATERIALS AND METHODS: We develop theoretical models to describe irrigation flow in an idealized setup and compare with benchtop experiments for flow through a straight scope, a scope with a deflected tip, and a scope with a working tool inserted. The benchtop experiments were performed using Boston Scientific LithoVue ureteroscope and a variety of Boston Scientific working tools. Standard ureteroscope working channels have circular cross sections, but using theoretical models we investigate whether modifications to the cross-sectional geometry can enhance flow rates. RESULTS: The theoretical flow predictions are confirmed by experimental results. Tip deflection is shown to have a negligible effect on flow rate, but the presence of working tools decreases flow significantly (for a fixed driving pressure). Flow rate is predicted to improve when tools are placed at the edge of the channel, rather than the center, and modifying the cross-sectional shape from a circle to an ellipse can further increase flow rate. CONCLUSIONS: A mathematical framework is formulated and shown to accurately predict the properties of ureteroscope irrigation flow. The theoretical approach has significant potential in quantifying irrigation flow and improving ureteroscope design.

Genetic variants of calcium and vitamin D metabolism in kidney stone disease.

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.