Shockwave lithotripsy compared with ureteroscopic stone treatment for adults with ureteric stones: the TISU non-inferiority RCT.

BACKGROUND: Urinary stone disease affects 2-3% of the general population. Ureteric stones are associated with severe pain and can have a significant impact on a patient's quality of life. Most ureteric stones are expected to pass spontaneously with supportive care; however, between one-fifth and one-third of patients require an active intervention. The two standard interventions are shockwave lithotripsy and ureteroscopic stone treatment. Both treatments are effective, but they differ in terms of invasiveness, anaesthetic requirement, treatment setting, number of procedures, complications, patient-reported outcomes and cost. There is uncertainty around which is the more clinically effective and cost-effective treatment. OBJECTIVES: To determine if shockwave lithotripsy is clinically effective and cost-effective compared with ureteroscopic stone treatment in adults with ureteric stones who are judged to require active intervention. DESIGN: A pragmatic, multicentre, non-inferiority, randomised controlled trial of shockwave lithotripsy as a first-line treatment option compared with primary ureteroscopic stone treatment for ureteric stones. SETTING: Urology departments in 25 NHS hospitals in the UK. PARTICIPANTS: Adults aged ≥ 16 years presenting with a single ureteric stone in any segment of the ureter, confirmed by computerised tomography, who were able to undergo either shockwave lithotripsy or ureteroscopic stone treatment and to complete trial procedures. INTERVENTION: Eligible participants were randomised 1 : 1 to shockwave lithotripsy (up to two sessions) or ureteroscopic stone treatment. MAIN OUTCOME MEASURES: The primary clinical outcome measure was resolution of the stone episode (stone clearance), which was operationally defined as 'no further intervention required to facilitate stone clearance' up to 6 months from randomisation. This was determined from 8-week and 6-month case report forms and any additional hospital visit case report form that was completed by research staff. The primary economic outcome measure was the incremental cost per quality-adjusted life-year gained at 6 months from randomisation. We estimated costs from NHS resources and calculated quality-adjusted life-years from participant completion of the EuroQol-5 Dimensions, three-level version, at baseline, pre intervention, 1 week post intervention and 8 weeks and 6 months post randomisation. RESULTS: In the shockwave lithotripsy arm, 67 out of 302 (22.2%) participants needed further treatment. In the ureteroscopic stone treatment arm, 31 out of 302 (10.3%) participants needed further treatment. The absolute risk difference was 11.4% (95% confidence interval 5.0% to 17.8%); the upper bound of the 95% confidence interval ruled out the prespecified margin of non-inferiority (which was 20%). The mean quality-adjusted life-year difference (shockwave lithotripsy vs. ureteroscopic stone treatment) was -0.021 (95% confidence interval 0.033 to -0.010) and the mean cost difference was -£809 (95% confidence interval -£1061 to -£551). The probability that shockwave lithotripsy is cost-effective is 79% at a threshold of society's willingness to pay for a quality-adjusted life-year of £30,000. The CEAC is derived from the joint distribution of incremental costs and incremental effects. Most of the results fall in the south-west quadrant of the cost effectiveness plane as SWL always costs less but is less effective. LIMITATIONS: A limitation of the trial was low return and completion rates of patient questionnaires. The study was initially powered for 500 patients in each arm; however, the total number of patients recruited was only 307 and 306 patients in the ureteroscopic stone treatment and shockwave lithotripsy arms, respectively. CONCLUSIONS: Patients receiving shockwave lithotripsy needed more further interventions than those receiving primary ureteroscopic retrieval, although the overall costs for those receiving the shockwave treatment were lower. The absolute risk difference between the two clinical pathways (11.4%) was lower than expected and at a level that is acceptable to clinicians and patients. The shockwave lithotripsy pathway is more cost-effective in an NHS setting, but results in lower quality of life. FUTURE WORK: (1) The generic health-related quality-of-life tools used in this study do not fully capture the impact of the various treatment pathways on patients. A condition-specific health-related quality-of-life tool should be developed. (2) Reporting of ureteric stone trials would benefit from agreement on a core outcome set that would ensure that future trials are easier to compare. TRIAL REGISTRATION: This trial is registered as ISRCTN92289221. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 19. See the NIHR Journals Library website for further project information.

Approximately 1 in 20 people suffers from kidney stones that pass down the urine drainage tube (ureter) into the urinary bladder and cause episodes of severe pain (ureteric colic). People with ureteric colic attend hospital for pain relief and diagnosis. Although most stones smaller than 10 mm eventually reach the bladder and are passed during urination, some get stuck and have to be removed using telescopic surgery (called ureteroscopic stone treatment) or shockwave therapy (called shockwave lithotripsy). Ureteroscopic stone treatment involves passing a telescope-containing instrument through the bladder and into the ureter to fragment and/or remove the stone. This is usually carried out under general anaesthetic as a day case. For shockwave lithotripsy, the patient lies flat on a couch and the apparatus underneath them generates shockwaves that pass through the skin to the ureter and break the stones into smaller fragments, which can be passed naturally in the urine. This involves using X-ray or ultrasound to locate the stone, but can be carried out on an outpatient basis and without general anaesthetic. Telescopic surgery is known to be more successful at removing stones after just one treatment, but it requires more time in hospital and has a higher risk of complications than shockwave lithotripsy (however, shockwave lithotripsy may require more than one session of treatment). Our study, the Therapeutic Interventions for Stones of the Ureter trial, was designed to establish if treatment for ureteric colic should start with telescopic surgery or shockwave therapy. Over 600 NHS patients took part and they were split into two groups. Each patient had an equal chance of their treatment starting with either telescopic surgery or shockwave lithotripsy, which was decided by a computer program (via random allocation). We counted how many patients in each group had further procedures to remove their stone. We found that telescopic surgery was 11% more effective overall, with an associated slightly better quality of life (10 more healthy days over the 6-month period), but was more expensive in an NHS setting. The finding of a lack of any significant additional clinical benefit leads to the conclusion that the more cost-effective treatment pathway is shockwave lithotripsy with telescopic surgery used only in those patients in whom shockwave lithotripsy is unsuccessful.

Evidence and clinical trials in Endourology: where are we going.

PURPOSE OF REVIEW: There is an ongoing explosion in the amount and quality, of research in the field of Endourology. From a solid basis of systematic reviews and small, single centre trials it has been possible to design large randomised controlled trials in the UK and in the USA. This review will describe some of the more recent trials (small and large) that are helping to provide a solid evidence base for our practice in Endourology. ONGOING STUDIES: Randomised controlled trial (RCTs) include: The Therapeutic Interventions for Stones in the Ureter (TISU), the Percutaneous nephrolithotomy, flexible Ureterorenoscopy and extracorporeal Shockwave lithotripsy for lower pole kidney stones (PURE RCTs) and the Prevention of Urinary Stones with Hydration (PUSH). Quality of life (QoL) measures and studies include: the Wisconsin Stone QoL Questionnaire, the Cambridge Renal Stone PROM, the Cambridge Ureteral Stone PROM, the Urinary stone and Intervention QoL questionnaire and the Study to Enhance Understanding of sTent-associated Symptoms (STENTS). The Core Outcome Set in Trials on treatments for Renal and UreteriC sTones (COSTRUCT) study aims to define a core outcome set to be used in future trials. SUMMARY: On-going studies will provide higher quality evidence on the treatment of ureteric and renal stones to inform treatment decision making and guideline recommendations. They will also guide decisions relating to prevention and recurrence and give insight into the true impact of urinary stones and endourological interventions on patients' quality of life. Future studies will incorporate big data and artificial intelligence.

Survey on ureTEric draiNage post uncomplicaTed ureteroscopy (STENT).

Objectives: To assess the feasibility of conducting a randomised controlled trial (RCT) to assess whether avoiding ureteric drainage is superior to performing ureteric drainage after Uncomplicated Ureteroscopy and/or Flexible Ureterorenoscopy (URS/FURS) treatment of a urinary tract stone in improving patient reported outcome measures (PROMs) and 30-day unplanned readmission rates. A secondary objective was to understand current practice of urologists regarding ureteric drainage after uncomplicated URS/FURS (UU). Material and methods: We undertook an online survey of urologists, circulated amongst members of international urological societies and through social media platforms. Uncomplicated URS/FURS was defined as completion of URS/FURS treatment for a urinary tract stone, with the absence of: ureteral trauma, residual fragments requiring further lithotripsy procedures, significant bleeding, perforation, prior urinary tract infection or pregnancy. The ureteric drainage options considered included an indwelling stent, stent on a string or a ureteric catheter. The primary outcome was to determine the proportion of urologists willing to take part in a RCT, randomising patients after UU to a "no ureteric drainage" arm or ureteric drainage arm. Secondary outcomes included determining in their current practice, the proportion of clinicians performing routine ureteric drainage after UU, the reasons for performing ureteric drainage following UU and their preferred optimal duration for ureteric drainage if it is used. The study was reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: Total of 468 respondents from 45 countries took part in the survey, of whom 303 completed the entire survey (65%). The majority agreed that they would be willing to randomise patients (244/303, 81%) in the proposed RCT. Perceived lack of equipoise to randomise was the most common reason for not being willing to participate (59/303, 19%).92% (308/335) reported that they use ureteric drainage after UU. This was most often due to wanting to prevent possible complications from post-operative ureteric oedema (77%) or to aid passage of small fragments (43%). Complexity of the case (i.e. impacted stone 90%) and length of the procedure (46%) were the most important intraoperative factors influencing the decision to use ureteric drainage post procedure. If required, the median stated ideal duration of ureteric drainage was 5 days (IQR: 3-7 days) after UU. If having UU personally, 30% would want no stent postoperatively and over half would prefer a stent on a string. Conclusion: We have highlighted wide variation in practice regarding ureteric drainage after UU. Our results support the feasibility of an RCT evaluating if no ureteric drainage is superior to ureteric drainage in improving PROMs and 30-day unplanned readmission rates following UU.

TISU: Extracorporeal shockwave lithotripsy, as first treatment option, compared with direct progression to ureteroscopic treatment, for ureteric stones: study protocol for a randomised controlled trial.

BACKGROUND: Urinary stone disease is very common with an estimated prevalence among the general population of 2-3%. Ureteric stones are associated with severe pain as they pass through the urinary tract and have significant impact on patients' quality of life due to the detrimental effect on their ability to work and need for hospitalisation. Most ureteric stones can be expected to pass spontaneously with supportive care. However, between one-fifth and one-third of cases require an intervention. The two standard active intervention options are extracorporeal shockwave lithotripsy (ESWL) and ureteroscopic stone retrieval. ESWL and ureteroscopy are effective in terms of stone clearance; however, they differ in terms of invasiveness, anaesthetic requirement, treatment setting, complications, patient-reported outcomes (e.g. pain after intervention, time off work) and cost. There is uncertainty around which is the most clinically effective in terms of stone clearance and the true cost to the NHS and to society (in terms of impact on patient-reported health and economic burden). The aim of this trial is to determine whether, in adults with ureteric stones, judged to require active intervention, ESWL is not inferior and is more cost-effective compared to ureteroscopic treatment as the initial management option. METHODS: The TISU study is a pragmatic multicentre non-inferiority randomised controlled trial of ESWL as the first treatment option compared with direct progression to ureteroscopic treatment for ureteric stones. Patients aged over 16 years with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) will be randomised to either ESWL or ureteroscopy. The primary clinical outcome is resolution of the stone episode (no further intervention required to facilitate stone clearance) up to six months from randomisation. The primary economic outcome is the incremental cost per quality-adjusted life years (QALYs) gained at six months from randomisation. DISCUSSION: Determining whether ESWL is not inferior clinically and is cost-effective compared to ureteroscopic treatment as the initial management in adults with ureteric stones who are judged to require active treatment is relevant not only to patients and clinicians but also to healthcare providers, both in the UK and globally. TRIAL REGISTRATION: ISRCTN registry, ISRCTN92289221 . Registered on 21 February 2013.

Urethral injection therapy for urinary incontinence in women.

BACKGROUND: Urinary incontinence imposes a significant health and economic burden to society. Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used as one the surgical treatments of stress urinary incontinence (SUI) in adult women. OBJECTIVES: To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS: Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable therapy with respect to continence grade (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (mean difference (MD) 0.54, 95% CI 0.16 to 0.92). Another trial, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610.12) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in RevMan) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS: The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects. Also, a Brief Economic Commentary (BEC) identified three studies suggesting that urethral bulking agent might be more cost-effective compared with retropubic mid-urethral slings, transobturator or traditional sling procedure when used as an initial treatment in women without hypermobility or as a follow-up to surgery failure provided injection is kept minimal. However, urethral bulking agent might not be cost-effective when compared with traditional sling as an initial treatment of SUI when a patient is followed up for a longer period (15 months post-surgery).

Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).

BACKGROUND: Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. OBJECTIVES: To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. DESIGN: A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. SETTING: Urology departments in 24 UK NHS hospitals. PARTICIPANTS: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. INTERVENTIONS: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. MAIN OUTCOME MEASURES: The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks. RESULTS: Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location. CONCLUSIONS: Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 µg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION: Tamsulosin 400 µg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Systematic review and meta-analysis of the clinical effectiveness of shock wave lithotripsy, retrograde intrarenal surgery, and percutaneous nephrolithotomy for lower-pole renal stones.

UNLABELLED: The prevalence of urolithiasis is increasing. Lower-pole stones (LPS) are the most common renal calculi and the most likely to require treatment. A systematic review comparing shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) in the treatment of ≤20 mm LPS in adults was performed. Comprehensive searches revealed 2741 records; 7 randomised controlled trials (RCTs) recruiting 691 patients were included. Meta-analyses for stone-free rate (SFR) at ≤3 mo favoured PNL over SWL (risk ratio [RR]: 2.04; 95% confidence interval [CI], 1.50-2.77) and RIRS over SWL (RR: 1.31; 95% CI, 1.08-1.59). Stone size subgroup analyses revealed PNL and RIRS were considerably more effective than SWL for >10 mm stones, but the magnitude of benefit was markedly less for ≤10 mm stones. The quality of evidence (Grading of Recommendations Assessment, Development, and Evaluation [GRADE]) for SFR was moderate for these comparisons. The median SFR from reported RCTs suggests PNL is more effective than RIRS. The findings regarding other outcomes were inconclusive because of limited and inconsistent data. Well-designed, prospective, comparative studies that measure these outcomes using standardised definitions are required, particularly for the direct comparison of PNL and RIRS. This systematic review, which used Cochrane methodology and GRADE quality-of-evidence assessment, provides the first level 1a evidence for the management of LPS. PATIENT SUMMARY: We thoroughly examined the literature to compare the benefits and harms of the different ways of treating kidney stones located at the lower pole. PNL and RIRS were superior to SWL in clearing the stones within 3 mo, but we were unable to make any conclusions regarding other outcomes. More data is required from reliable studies before firm recommendations can be made.

Fate of indeterminate lesions detected on noncontrast computed tomography scan for suspected urolithiasis: a retrospective cohort study with a minimum follow-up of 15 months.

OBJECTIVE: To investigate the fate of indeterminate lesions incidentally found on noncontrast computed tomography (NCCT) for suspected urolithiasis. METHODS: A retrospective review of 404 consecutive cases of suspected urolithiasis was undertaken between May 2010 and April 2011. Data were collected for patient demographics, presence of calculus disease, and additional urologic or nonurologic pathologies and their clinical relevance. The indeterminate or suspicious lesions were followed up and the data were reviewed in September 2012. RESULTS: In total, 404 patients underwent NCCT for renal colic (mean age, 50 years [range, 13-91 years]; 165 females). Minimum follow-up period was 15 months. Fifty-eight patients (14%) had ureteric, 85 (21%) had renal, and 39 patients (10%) had combined ureteric and renal stones. Noncalculus pathologies were found in 107 patients (26%). Sixty patients (15%) had indeterminate lesions. Of these patients, 6 required operative intervention, 35 had a benign diagnosis after further imaging and multidisciplinary team meeting, and 13 remained under surveillance after 1 year. Indeterminate pulmonary lesions (8 of 16) were the commonest lesions to remain under surveillance. CONCLUSION: NCCT is vital for the diagnosis of urolithiasis with a pick up rate of 45% and remains the standard of care. However, with incidental detection of potential malignant lesions, a significant minority will need close monitoring, intervention, or both. In our study, approximately one-third of these lesions either remained under surveillance or had intervention.

Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies made such data difficult to interpret. There was no evidence of any statistically significant difference between pazopanib and best supportive care (HR 0.501; 95 % CI 0.136, 2.348). In the indirect comparison, there were no statistically significant differences between pazopanib and IFN-α (HR 0.627; 95 % CI 0.173, 2.269) or between pazopanib and sunitinib (HR 0.969; 95 % CI 0.359, 2.608). Based upon the work presented including a 12.5 % discount for pazopanib, sunitinib was extendedly dominated by a combination of pazopanib and IFN-α. As a consequence, the incremental cost per QALY for pazopanib versus IFN-α was £38,925. The results were not greatly altered over the range of univariate deterministic sensitivity analyses conducted by the manufacturer but pair-wise probabilistic sensitivity analyses suggested that given a threshold value of £30,000, there is a 54 % probability that pazopanib was preferred to sunitinib, 40 % chance against IFN-α and 47 % chance against best supportive care. The Appraisal Committee concluded that pazopanib should be recommended as a first-line treatment option for people with advanced renal cell carcinoma who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and if the manufacturer provides pazopanib with a 12.5 % discount on the list price and provides a possible future rebate linked to the outcome of the head-to-head COMPARZ trial, as agreed under the terms of the patient access scheme and to be confirmed when the COMPARZ trial data are made available.

Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for ureteric calculi.

BACKGROUND: Ureteral stones frequently cause renal colic, and if left untreated, can lead to obstructive uropathy. Extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy, with or without intracorporeal lithotripsy, are the most common interventions used to treat ureteral stones. ESWL treatment is less invasive than ureteroscopy, but has some limitations such as a high retreatment rate, and is not available in all centres. Recent advances in ureteroscopy have increased success rates and reduced complication rates. OBJECTIVES: To examine evidence from randomised controlled trials (RCTs) on the outcomes of ESWL or ureteroscopy in the treatment of ureteric calculi. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL, Clinicaltrials.gov, Google Scholar, reference lists of articles and abstracts from conference proceedings, all without language restriction. SELECTION CRITERIA: RCTs that compared ESWL with ureteroscopic retrieval of ureteric stones were included in this review. Study participants were adults with ureteric stones requiring intervention. Published and unpublished sources were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three authors independently assessed study quality, risk of bias, and extracted data. Statistical analyses were performed using the random-effects model. Results were expressed as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous data, both with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1205 patients) were included in the review. Stone-free rates were lower in patients who underwent ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re-treatment rates were lower in ureteroscopy patients (6 studies, 1049 participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to 0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to 0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55 days, 95% CI -3.24 to -1.86).Three studies adequately described the randomisation sequence, three studies were unclear on how they randomised, while one study had a high risk of selection bias. All the studies had an unclear risk of performance bias and detection bias, while all had a low risk of attrition bias, reporting bias, or other sources of bias identified. AUTHORS' CONCLUSIONS: Compared with ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free state, but with a higher complication rate and longer hospital stay.

Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy.

BACKGROUND: Surgery performed to improve or replace the function of the diseased urinary bladder has been carried out for over a century. Main reasons for improving or replacing the function of the urinary bladder are bladder cancer, neurogenic bladder dysfunction, detrusor overactivity and chronic inflammatory diseases of the bladder (such as interstitial cystitis, tuberculosis and schistosomiasis). There is still much uncertainty about the best surgical approach. Options available at the present time include: (1) conduit diversion (the creation of various intestinal conduits to the skin) or continent diversion (which includes either a rectal reservoir or continent cutaneous diversion), (2) bladder reconstruction and (3) replacement of the bladder with various intestinal segments. OBJECTIVES: To determine the best way of improving or replacing the function of the lower urinary tract using intestinal segments when the bladder has to be removed or when it has been rendered useless or dangerous by disease. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 28 October 2011), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and CINAHL, and handsearching of journals and conference proceedings, and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of surgery involving transposition of an intestinal segment into the urinary tract. DATA COLLECTION AND ANALYSIS: Trials were evaluated for appropriateness for inclusion and for risk of bias by the review authors. Three review authors were involved in the data extraction. Data were combined in a meta-analysis when appropriate. MAIN RESULTS: Five trials met the inclusion criteria with a total of 355 participants. These trials addressed only five of the 14 comparisons pre-specified in the protocol. One trial reported no statistically significant differences in the incidence of upper urinary tract infection, uretero-intestinal stenosis and renal deterioration in the comparison of continent diversion with conduit diversion. The confidence intervals were all wide, however, and did not rule out important clinical differences. In a second trial, there was no reported difference in the incidence of upper urinary tract infection and uretero-intestinal stenosis when conduit diversions were fashioned from either ileum or colon. A meta-analysis of two trials showed no statistically significant difference in daytime or nocturnal incontinence amongst participants who were randomised to ileocolonic/ileocaecal segment bladder replacement compared to an ileal bladder replacement. However, one small trial suggested that bladder replacement using an ileal segment compared to using an ileocolonic segment may be better in terms of lower rates of nocturnal incontinence. There were no differences in the incidence of dilatation of upper tract, daytime urinary incontinence or wound infection using different intestinal segments for bladder replacement. However the data were reported for 'renal units', but not in a form that allowed appropriate patient-based paired analyses. No statistically significant difference was found in the incidence of renal scarring between anti-refluxing versus freely refluxing uretero-intestinal anastomotic techniques in conduit diversions and bladder replacement groups. Again, the outcome data were not reported as paired analysis or in form to carry out paired analysis. AUTHORS' CONCLUSIONS: The evidence from the included trials was very limited. Only five studies met the inclusion criteria; these were small, of moderate or poor methodological quality, and reported few of the pre-selected outcome measures. This review did not find any evidence that bladder replacement (orthotopic or continent diversion) was better than conduit diversion following cystectomy for cancer. There was no evidence to suggest that bladder reconstruction was better than conduit diversion for benign disease. The clinical significance of data from one small trial suggesting that bladder replacement using an ileal segment compared to using an ileocolonic segment is better in terms of lower rates of nocturnal incontinence is uncertain. The small amount of usable evidence for this review suggests that collaborative multi centre studies should be organised, using random allocation where possible.

Urethral injection therapy for urinary incontinence in women.

BACKGROUND: Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used for the treatment of stress urinary incontinence in adult women. OBJECTIVES: To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS: Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable with respect to continence grade (risk ratio (RR) 0.7, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (RR 0.54, 95% CI 0.16 to 0.92). Another, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in Revman) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS: The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects.

Metastatic Crohn's disease of the penis: two cases.

Metastatic Crohn's disease is a rare inflammatory process that is non-contiguous from the bowel. It can affect the penis and is variable in presentation and onset in relation to bowel symptoms. It has been treated with oral, topical, systemic, and surgical therapies. We describe our experience with two cases of penile metastatic Crohn's disease and their management in comparison with other cases described in the literature. Both our patients were of the lymphoedematous type and had sexual and voiding dysfunction. They were treated with topical and intra-lesional steroids and circumcision after unsuccessful systemic treatments.

Surgical treatments for men with benign prostatic enlargement: cost effectiveness study.

OBJECTIVE: To determine which surgical treatment for lower urinary tract symptoms suggestive of benign prostate enlargement is cost effective. DESIGN: Care pathways describing credible treatment strategies were decided by consensus. Cost-utility analysis used Markov modelling and Monte Carlo simulation. DATA SOURCES: Clinical effectiveness data came from a systematic review and an individual level dataset. Utility values came from previous economic evaluations. Costs were calculated from National Health Service (NHS) and commercial sources. METHODS: The Markov model included parameters with associated measures of uncertainty describing health states between which individuals might move at three monthly intervals over 10 years. Successive annual cohorts of 25,000 men were entered into the model and the probability that treatment strategies were cost effective was assessed with Monte Carlo simulation with 10,000 iterations. RESULTS: A treatment strategy of initial diathermy vaporisation of the prostate followed by endoscopic holmium laser enucleation of the prostate in case of failure to benefit or subsequent relapse had an 85% probability of being cost effective at a willingness to pay value of pound20,000 (euro21,595, $28,686)/quality adjusted life year (QALY) gained. Other strategies with diathermy vaporisation as the initial treatment were generally cheaper and more effective than the current standard of transurethral resection repeated once if necessary. The use of potassium titanyl phosphate laser vaporisation incurred higher costs and was less effective than transurethral resection, and strategies involving initial minimally invasive treatment with microwave thermotherapy were not cost effective. Findings were unchanged by wide ranging sensitivity analyses. CONCLUSION: The outcome of this economic model should be interpreted cautiously because of the limitations of the data used. The finding that initial vaporisation followed by holmium laser enucleation for failure or relapse might be advantageous both to men with lower urinary tract symptoms and to healthcare providers requires confirmation in a good quality prospective clinical trial before any change in current practice. Potassium titanyl phosphate laser vaporisation was unlikely to be cost effective in our model, which argues against its unrestricted use until further evidence of effectiveness and cost reduction is obtained.