Ureteral Calculi EAU/AUA Nephrolithiasis Guideline Panel Members: Glenn M. Preminger, M.D., Co-Chair Hans-Göran Tiselius, M.D., Ph.D., Co-Chair Dean G. Assimos, M.D., Vice Chair Peter Alken, M.D., Ph.D. A. Colin Buck, M.D., Ph.D. Michele Gallucci, M.D., Ph.D. Thomas Knoll, M.D., Ph.D. James E. Lingeman, M.D. Stephen Y. Nakada, M.D. Margaret Sue Pearle, M.D., Ph.D. Kemal Sarica, M.D., Ph.D. Christian Türk, M.D., Ph.D. J. Stuart Wolf, Jr., M.D. Consultants: Hanan S. Bell, Ph.D. Patrick M. Florer AUA and EAU Staff: Gunnar Aus, M.D., Ph.D., EAU Guidelines Office Chair Heddy Hubbard, Ph.D. Edith Budd Karin Plass Michael Folmer Katherine Moore Kadiatu Kebe MedicalWriting Assistance: Diann Glickman, PharmD 2007 Guideline for the Management of Ureteral Calculi Chapter 1: The Management of Ureteral Calculi: Diagnosis and Treatment Recommendations Table of Contents Introduction..................................................................................................................................... 3 Methodology ................................................................................................................................... 4 Results of the Outcomes Analysis ................................................................................................ 12 Observation and Medical Therapies ......................................................................................... 12 Shock-wave Lithotripsy and Ureteroscopy............................................................................... 13 Efficacy Outcomes.................................................................................................................... 15 Procedure Counts...................................................................................................................... 22 Complications ........................................................................................................................... 27 Other Surgical Interventions..................................................................................................... 30 The Index Patient .......................................................................................................................... 30 Treatment Guidelines for the Index Patient .................................................................................. 31 For All Index Patients ............................................................................................................... 31 For Ureteral Stones <10 mm..................................................................................................... 31 For Ureteral Stones >10 mm..................................................................................................... 33 For Patients Requiring Stone Removal..................................................................................... 34 Recommendations for the Pediatric Patient.............................................................................. 36 Recommendations for the Nonindex Patient ............................................................................ 37 Discussion ..................................................................................................................................... 37 Medical Expulsive Therapy ...................................................................................................... 38 Shock-wave Lithotripsy............................................................................................................ 39 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 1 Ureteroscopy............................................................................................................................. 42 Percutaneous Antegrade Ureteroscopy..................................................................................... 44 Laparoscopic and Open Stone Surgery..................................................................................... 45 Special Considerations.............................................................................................................. 46 Pregnancy ................................................................................................................. 46 Pediatrics .................................................................................................................. 47 Cystine Stones ........................................................................................................... 48 Uric acid Stones ........................................................................................................ 49 Research and Future Directions .................................................................................................... 49 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 2 Introduction The American Urological Association (AUA) Nephrolithiasis Clinical Guideline Panel was established in 1991. Since that time, the Panel has developed three guidelines on the management of nephrolithiasis, the most recent being a 2005 update of the original 1994 Report on the Management of Staghorn Calculi.1 The European Association of Urology (EAU) began their nephrolithiasis guideline project in 2000, yielding the publication of Guidelines on Urolithiasis, with updates in 2001 and 2006.2 While both documents provide useful recommendations on the management of ureteral calculi, changes in shock-wave lithotripsy (SWL) technology, endoscope design, intracorporeal lithotripsy techniques, and laparoscopic expertise have burgeoned over the past five to ten years. Under the sage leadership of the late Dr. Joseph W. Segura, the AUA Practice Guidelines Committee suggested to both the AUA and the EAU that they join efforts in developing the first set of internationally endorsed guidelines focusing on the changes introduced in ureteral stone management over the last decade. We therefore dedicate this report to the memory of Dr. Joseph W. Segura whose vision, integrity, and perseverance led to the establishment of the first international guideline project. This joint EAU/AUA Nephrolithiasis Guideline Panel (hereinafter the Panel) performed a systematic review of the English language literature published since 1997 and a comprehensively analyzed outcomes data from the identified studies. Based on their findings, the Panel concluded that when removal becomes necessary, SWL and ureteroscopy (URS) remain the two primary treatment modalities for Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 3 the management of symptomatic ureteral calculi. Other treatments were reviewed, including medical expulsive therapy (MET) to facilitate spontaneous stone passage, percutaneous antegrade ureteroscopy, and laparoscopic and open surgical ureterolithotomy. In concurrence with the previously published guidelines of both organizations, open stone surgery is still considered a secondary treatment option. Blind basketing of ureteral calculi is not recommended. In addition, the Panel was able to provide some guidance regarding the management of pediatric patients with ureteral calculi. The Panel recognizes that some of the treatment modalities or procedures recommended in this document require access to modern equipment or presupposes a level of training and expertise not available to practitioners in many clinical centers. Those situations may require physicians and patients to resort to treatment alternatives. This article will be published simultaneously in European Urology and The Journal of Urology. The Panel believes that future collaboration between the EAU and the AUA will serve to establish other internationally approved guidelines, offering physician and patient guidance worldwide. Methodology The Panel initially discussed the scope of the guideline and the methodology, which would be similar to that used in developing the previous AUA guideline. All treatments commonly employed in the United States and/or Europe were included in this report except for those that were explicitly excluded in the previous guideline or newer treatments for which insufficient literature existed. In the analysis, patient data were stratified by age (adult versus child), stone size, stone location, and stone composition. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 4 Later, however, the data were found to be insufficient to allow analysis by composition. The outcomes deemed by the Panel to be of particular interest to the patient included the following: stone-free rate, number of procedures performed, stone-passage rate or probability of spontaneous passage, and complications of treatment. The Panel did not examine economic effects, including treatment costs. Outcomes were stratified by stone location (proximal, mid, and distal ureter) and by stone size (dichotomized as ≤10 mm and >10 mm for surgical interventions, and ≤5 mm and >5 mm for medical interventions and observation where possible; exceptions were made when data were reported, for example as <10 mm and ≥10 mm). The mid ureter is the part of the ureter that overlies the bony pelvis, i.e., the position of the ureter that corresponds to the sacroiliac joint; the proximal ureter is above and the distal ureter is below. Treatments were divided into three broad groups: 1. Observation and medical therapy 2. Shock-wave lithotripsy and ureteroscopy 3. Open surgery, laparoscopic stone removal, or percutaneous antegrade ureteroscopy. The review of the evidence began with a literature search and data extraction. Articles were selected from a database of papers derived from MEDLINE searches dealing with all forms of urinary tract stones. This database was maintained by a Panel chair. The abstract of each paper was independently reviewed by an American and a European Panel member, and articles were selected for data extraction if any panel member felt it might have useful data. Additional articles were suggested by Panel members or found as references in review articles. In total, 348 citations entered the Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 5 extraction process. An American and a European Panel member each independently extracted data from each article onto a standardized form. The team members reconciled the extractions, and the data were entered into a Microsoft Access® (Microsoft, Redmond, WA) database. The Panel scrutinized the entries, reconciled the inconsistencies in recording, corrected the extraction errors, and excluded some articles from further analysis for the following reasons: 1. The article was included in the previous guideline. 2. The article did not provide usable data on the outcomes of interest. 3. Results for patients with ureteral stones could not be separated from results for those with renal stones. 4. The treatments used were not current or were not the focus of the analysis. 5. The article was a review article of data reported elsewhere. 6. The article dealt only with salvage therapy. A total of 244 of the 348 articles initially selected had extractable data. Articles excluded from evidence combination remained candidates for discussion in the text of the guideline. The goal was to generate outcomes tables comparing estimates of outcomes across treatment modalities. To generate an outcomes table, estimates of the probabilities and/or magnitudes of the outcomes are required for each intervention. Ideally, these are derived from a synthesis or combination of the evidence. Such a combination can be performed in a variety of ways depending on the nature and quality of the evidence. For this report, the Panel elected to use the Confidence Profile Method3, which provides Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 6 methods for analyzing data from studies that are not randomized controlled trials (RCTs). The Fast*Pro computer software4 was used in the analysis. This program provides posterior distributions from meta-analyses from which the median can be used as a best estimate, and the central 95% of the distribution serves as a confidence interval (CI). Statistical significance at the p<0.05 level (two-tailed) was inferred when zero was not included in the CI. Because of the paucity of controlled trials found on literature review, however, the outcome for each intervention was estimated by combining single arms from various clinical series. These clinical series frequently had very different outcomes, likely due to a combination of site-to-site variations in patient populations, in the performance of the intervention, in the skill of those performing the intervention, and different methods of determining stone-free status. Given these differences, a random-effects, or hierarchical, model was used to combine the studies. Evidence from the studies meeting the inclusion criteria and reporting a given outcome was combined within each treatment modality. Graphs showing the results for each modality were developed to demonstrate similarities and differences between treatments. The available data for procedures per patient would not permit a statistical analysis using these techniques. Unlike the binary outcome of stone-free status (the patient either is or is not stone free), the number of procedures per patient is a discrete rate. In some cases discrete rates can be approximated with a continuous rate, but in order to meta-analyze continuous rates, a measure of variance (e.g., standard deviation, standard error) is needed in addition to the mean. Unfortunately, measures of variance Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 7 were rarely reported in the studies reviewed. As a result, numbers of procedures per patient were evaluated by calculating the average across studies weighted by the number of patients in each study. Procedures per patient were counted in three totals: primary procedures, secondary procedures, and adjunctive procedures. Primary procedures were all consecutive procedures of the same type aimed at removing the stone. Secondary procedures were all other procedures used to remove the stone. Adjunctive procedures were defined as additional procedures that do not involve active stone removal. One difficulty in estimating the total number of procedures per patient is that secondary and adjunctive procedures were not reported consistently. Since the Panel had decided to analyze primary, secondary, and adjunctive procedures separately, only studies that specifically reported data on a type of procedure were included in estimates for that procedure type. This approach may have overestimated numbers of secondary and adjunctive procedures because some articles may not have reported that procedures were not performed. It is important to note that, for certain outcomes, more data were reported for one or another treatment modality. While resulting CIs reflect available data, the probabilities for certain outcomes can vary widely within one treatment modality. In addition, the fact that data from only a few RCTs could be evaluated may have somewhat biased results. For example, differences in patient selection may have had more weight in analyses than differing treatment effects. Nevertheless, the results obtained reflect the best outcome estimates presently available. Studies that reported numbers of patients who were stone free after primary procedures were included in the stone-free analysis. Studies that reported only the Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 8 combined number of patients who either were stone free or had “clinically insignificant fragments” were excluded. Many studies did not indicate how or when stone-free status was determined. The stone-free rate was considered at three time points: after the first procedure, after all consecutive procedures using the primary treatment, and after the total treatments. Initially, the Panel divided complications into three broad categories: acute, longterm, and medical; however, after examining the available evidence, the Panel determined that this breakdown was not useful. Several factors caused inaccuracy in the estimates, but did so in opposite directions, thereby reducing the magnitude of inaccuracy. For example, including studies that did not specifically mention that there were no occurrences of a specific complication may have led to overestimates of complication rates when meta-analyzed. By combining similar complications, the Panel also potentially mitigated the overestimate by making it more likely that a complication in the class was reported. The probability that a patient will have a complication may still be overstated slightly because some patients experienced multiple complications. Since the grouping of complications varies by study, the result of the meta-analysis is best interpreted as the mean number of complications that a patient may experience rather than as the probability of having a complication. Moreover, since reporting of complications is not consistent, the estimated rates given here are probably less accurate than the CIs would indicate. There were insufficient data to permit meaningful metaanalyses of patient deaths. Data analyses were conducted for two age groups. One analysis included studies of patients ages 18 or younger (or identified as pediatric patients in the article without Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 9 specifying age ranges). The adult analysis included all other studies even if children were included. After the evidence was combined and outcome tables were produced, the Panel met to review the results and identify anomalies. From the evidence in the outcome tables and expert opinion, the Panel drafted the treatment guidelines. In this guideline the standard, recommendations, and options given were rated according to the levels of evidence published from the U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research:5 Ia. Evidence obtained from meta-analysis of randomized trials Ib. Evidence obtained from at least one randomized trial IIa. Evidence obtained from at least one well-designed controlled study without randomization IIb. Evidence obtained from at least one other type of well-designed quasiexperimental study III. Evidence obtained from well-designed nonexperimental studies, such as comparative studies, correlation studies, and case reports IV. Evidence obtained from expert committee reports, or opinions, or clinical experience of respected authorities As in the previous AUA guideline, the present statements are graded with respect to the degree of flexibility in application. Although the terminology has changed slightly, from the original AUA reports, the current three levels are essentially the same. A "standard" is the most rigid treatment policy. A "recommendation" has significantly less Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 10 rigidity, and an "option" has the largest amount of flexibility. These terms are defined as follows: 1. Standard: A guideline statement is a standard if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions, and (2) there is virtual unanimity about which intervention is preferred. 2. Recommendation: A guideline statement is a recommendation if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions, and (2) an appreciable, but not unanimous majority agrees on which intervention is preferred. 3. Option: A guideline statement is an option if: (1) the health outcomes of the interventions are not sufficiently well known to permit meaningful decisions, or (2) preferences are unknown or equivocal. The draft was sent to 81 peer reviewers of whom 26 provided comments; the Panel revised the document based on the comments received. The guideline was submitted first for approval to the Practice Guidelines Committee of the AUA and the Guidelines Office of the EAU and then forwarded to the AUA Board of Directors and the EAU Board for final approval. The guideline is posted on the American Urological Association website, www.auanet.org, and on the European Association of Urology website, www.uroweb.org. Chapter 1 will be published in The Journal of Urology and in European Urology. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 11 Results of the Outcomes Analysis The results of the analysis described in this chapter provide most of the evidentiary basis for the guideline statements. Further details and tables corresponding to the figures in this section are found in Chapter 3 and the Appendixes. The panel’s attempt to differentiate results for pediatric patients from those for adults was not completely successful as most studies included both adults and children. Where possible, the panel performed two analyses, one including all studies regardless of patient age, and a second including only those studies or groups of patients that were comprised entirely of pediatric patients. Observation and Medical Therapies Stone-passage rates Only limited data were found on the topic of spontaneous passage by stone size. For stones ≤5 mm, meta-analysis of five patient groups (224 patients) yielded an estimate that 68% would pass spontaneously (95% CI: 46% to 85%]. For stones >5 mm and ≤10 mm, analysis of three groups (104 patients) yielded an estimate that 47% would pass spontaneously (95% CI: 36% to 59%). Details of the meta-analysis are presented in Appendixes 8 and 9. Two medical therapies had sufficient analyzable data: the calcium channel blocker nifedipine and alpha-receptor antagonists. Analyses of stone-passage rates were done in three ways. The first combined all single arms evaluating the therapies. Using this approach, meta-analysis of four studies of nifedipine (160 patients) yielded an estimate of a 75% passage rate (95% CI: 63% to 84%). Six studies examined alpha Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 12 blockers (280 patients); the meta-analysis yielded a stone-passage rate of 81% (95% CI: 72% to 88%). The second method was a standard Bayesian hierarchical meta-analysis of the available RCTs that compared either nifedipine or alpha blockers to control therapies. The results for nifedipine showed an absolute increase of 9% in stone-passage rates (95% CI: -7% to 25%), which was not statistically significant. Meta-analysis of alpha blockers versus control showed an absolute increase of 29% in the stone-passage rate (95% CI: 20% to 37%), which was statistically significant. The Panel also attempted to determine whether alpha blockers provide superior stone passage when compared to nifedipine. Two randomized controlled trials were identified. When hierarchical meta-analysis was performed on these two studies, tamsulosin provided an absolute increase in stone-passage rate of 14% (95% CI: -4% to 32%) which was not statistically significant. When nonhierarchical methods were used, the stone-passage improvement increased to 16% (95% CI: 7% to 26%) which was statistically significant. Finally, the Panel used the results of the meta-analyses versus controls (second method above) to determine the difference between alpha blockers and calcium channel blockers. This method allows the use of more data but is risky since it depends on the control groups having comparable results. The analysis yielded a 20% improvement in stone-passage rates with alpha blockers, and the 95% CI of 1% to 37% just reached statistical significance. Shock-wave Lithotripsy and Ureteroscopy Stone-free rates were analyzed for a number of variant methods of performing SWL and URS. The Panel attempted to differentiate between bypass, pushback, and in Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 13 situ SWL as well as differences between lithotripters. Most differences were minimal and did not reach statistical significance. For that reason, the data presented in this Chapter compare the meta-analysis of all forms of SWL to the meta-analysis of all forms of URS. The Panel also attempted to differentiate between flexible and rigid ureteroscopes. Details of the breakdowns by type of SWL and URS are given in Chapter 3. Data were analyzed for both efficacy and complications. Two efficacy outcomes were analyzed: stone-free rate and procedure counts. Complications were grouped into classes. The most important classes are reported herein. The full complication results are in Appendix 10. Analyses were performed for the following patient groups where data were available. 1. Proximal stones ≤10 mm 2. Proximal stones >10 mm 3. Proximal stones regardless of size 4. Mid-ureteral stones ≤10 mm 5. Mid-ureteral stones >10 mm 6. Mid-ureteral stones regardless of size 7. Distal stones ≤10 mm 8. Distal stones >10 mm 9. Distal stones regardless of size Analyses of pediatric groups were attempted for the same nine groups, although data were lacking for many groups. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 14 Efficacy Outcomes Stone-free rates The Panel decided to analyze a single stone-free rate. If the study reported the stone-free rate after all primary procedures, that number was used. If not and the study reported the stone-free rate after the first procedure, then that number was used. The intention of the Panel was to provide an estimate of the number of primary procedures and the stone-free rate after those procedures. There is a lack of uniformity in the literature in reporting the time to stone-free status, thereby limiting the ability to comment on the timing of this parameter. The results of the meta-analysis of stone-free data are presented for the overall group in Table 1 and Figure 1. The results are presented as medians of the posterior distribution (best central estimate) with 95% Bayesian CIs (credible intervals [CIs]). Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 15 Table 1. Stone-Free Rates for SWL and URS in the Overall Population Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 16 Figure 1. Stone-Free Rates for SWL and URS in the Overall Population Stone Free Rates after Primary/First Treatment Distal Ureter - SWL Distal Ureter - URS Distal Ureter < 10 mm - SWL Distal Ureter < 10 mm - URS Distal Ureter > 10 mm - SWL Distal Ureter > 10 mm - URS Mid Ureter - SWL Mid Ureter - URS Mid Ureter < 10 mm - SWL Mid Ureter < 10 mm - URS Mid Ureter > 10 mm - SWL Mid Ureter > 10 mm - URS Proximal Ureter - SWL Proximal Ureter - URS Proximal Ureter < 10 mm - SWL Proximal Ureter < 10 mm - URS Proximal Ureter > 10 mm - SWL Proximal Ureter > 10 mm - URS 0% 20% 40% 60% 80% 100% Estimated Occurrence Rate with 95% CI CI=confidence interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 17 This analysis shows that overall, for stones in the proximal ureter (n=8,670), there was no difference in stone-free rates between SWL and URS. However, for proximal ureteral stones <10 mm (n=1,129), SWL had a higher stone-free rate than URS, and for stones >10 mm (n=523), URS had superior stone-free rates. This difference arises because the stone-free rate for proximal ureteral stones treated with URS did not vary significantly with size, whereas the stone-free rate following SWL negatively correlated with stone size. For all distal stones, URS yields better stone-free rates overall and in both size categories. For all mid-ureteral stones, URS appears superior, but the small number of patients may have prevented results from reaching statistical significance. Unfortunately, RCTs comparing these treatments were generally lacking, making an accurate assessment impossible. However, the posterior distributions resulting from the meta-analysis can be subtracted, yielding a distribution for the difference between the treatments. If the CI of this result does not include zero, then the results may be considered to be statistically significantly different. This operation is mathematically justifiable but operationally risky: if the patients receiving different treatments are different or if outcome measures are different, results may be meaningless. Nonetheless, the Panel performed the comparison and found that URS stone-free rates were significantly better than SWL rates for distal ureteral stones ≤10 mm and >10 mm and for proximal ureteral stones >10 mm. The stone-free rate for mid-ureteral stones was not statistically significantly different between URS and SWL. The results with URS using a flexible ureteroscope for proximal ureteral stones appear better than those achieved with a rigid device, but not at a statistically significant level. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 18 Stone-free results for pediatric patients are shown in Table 2 and Figure 2. The very small number of patients in most groups, particularly for URS, makes comparisons among treatments difficult. However, it does appear that SWL may be more effective in the pediatric subset than in the overall population, particularly in the mid and lower ureter. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 19 Table 2. Stone-Free Rates for SWL and URS, Pediatric Population Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 20 Figure 2. Stone-Free Rates for SWL and URS, Pediatric Population Stone Free Rates after Primary/First Treatment Pediatric Patients Distal Ureter - SWL Distal Ureter - URS Distal Ureter < 10 mm - SWL Distal Ureter < 10 mm - URS Distal Ureter > 10 mm - SWL Mid Ureter - SWL Mid Ureter - URS Mid Ureter < 10 mm - SWL Mid Ureter > 10 mm - SWL Mid Ureter > 10 mm - URS Proximal Ureter - SWL Proximal Ureter - URS Proximal Ureter < 10 mm - SWL Proximal Ureter > 10 mm - SWL 0% 20% 40% 60% 80% 100% Estimated Occurrence Rate with 95% CI CI=confidence interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 21 Procedure Counts Procedure counts were captured as three types: 1. Primary procedures – the number of times the intended procedure was performed. 2. Secondary procedures – the number of times an alternative stone removal procedure(s) was performed. 3. Adjunctive procedures – additional procedures performed at a time other than when the primary or secondary procedures were performed; these could include procedures related to the primary/secondary procedures such as stent removals as well as procedures performed to deal with complications; most adjunctive procedures in the data presented represent stent removals. It is likely that many stent-related adjunctive procedures were underreported, and thus the adjunctive procedure count may be underestimated. As mentioned in Chapter 2, it was not possible to perform a meta-analysis or to test for statistically significant differences between treatments due to the lack of variance data, and only weighted averages could be computed. The procedure count results for the overall population are shown in Table 3 and Figure 3. Figure 3 results are presented as stacked bars. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 22 Table 3. Procedure Counts for SWL and URS in the Overall Population Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 23 Figure 3. Procedure Counts for SWL and URS in the Overall Population Procedures per Patient Distal Ureter - SWL Distal Ureter - URS Distal Ureter < 10 mm - SWL Distal Ureter < 10 mm - URS Distal Ureter > 10 mm - SWL Distal Ureter > 10 mm - URS Mid Ureter - SWL Mid Ureter - URS Mid Ureter < 10 mm - SWL Mid Ureter < 10 mm - URS Mid Ureter > 10 mm - SWL Mid Ureter > 10 mm - URS Proximal Ureter - SWL Proximal Ureter - URS Proximal Ureter < 10 mm - SWL Proximal Ureter < 10 mm - URS Proximal Ureter > 10 mm - SWL Proximal Ureter > 10 mm - URS 0.0 0.5 1.0 1.5 2.0 2.5 3.0 Weighted Mean Procedures per Patient Primary Procedures Secondary Procedures Adjunctive Procedures Procedure count results for pediatric patients are shown in Table 4 and Figure 4. Again, the numbers of patients with available data were small and did not support meaningful comparisons among treatments. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 24 Table 4. Procedure Counts for SWL and URS in the Pediatric Population, All Locations Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 25 Figure 4. Procedure Counts for SWL and URS in the Pediatric Population, All Locations Procedures per Patient - Pediatric Patients Distal Ureter - SWL Distal Ureter - URS Distal Ureter < 10 mm - SWL Distal Ureter < 10 mm - URS Distal Ureter > 10 mm - SWL Mid Ureter - SWL Mid Ureter - URS Mid Ureter < 10 mm - SWL Mid Ureter < 10 mm - URS Mid Ureter > 10 mm - SWL Mid Ureter > 10 mm - URS Proximal Ureter - SWL Proximal Ureter - URS Proximal Ureter < 10 mm - SWL Proximal Ureter < 10 mm - URS Proximal Ureter > 10 mm - SWL 0.0 0.5 1.0 1.5 2.0 2.5 Weighted Mean Procedures per Patient Primary Procedures Secondary Procedures Adjunctive Procedures Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 26 Complications The articles were extracted for various complications; however, the Panel believes the following are the most relevant: 1. Sepsis 2. Steinstrasse 3. Stricture 4. Ureteral injury 5. Urinary tract infection (UTI) Serious complications, including death and loss of kidney, were sufficiently rare that data were not available to estimate their rates of occurrence. Other complications are listed in Chapter 3. The complication rates for the overall population by treatment, size, and location are shown in Table 5. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 27 Table 5. Complications Occurrence Rates with SWL and URS, Overall Population SWL Groups/Patients Med/95% CI Distal Ureter Sepsis 6 2019 3% (2 - 5)% Steinstrasse 1 26 4% (0 - 17)% Stricture 2 609 Ureteral Injury UTI URS Groups/Patients Med/95% CI 7 1954 2% (1 - 4)% 0% (0 - 1)% 16 1911 1% (1 - 2)% 1 45 1% (0 - 5)% 23 4529 3% (3 - 4)% 3 87 4% (1 - 12)% 3 458 4% (2 - 7)% 2 398 5% (0 - 20)% 4 199 4% (1 - 11)% Steinstrasse 1 37 8% (2 - 20)% Stricture 1 43 1% (0 - 6)% 7 326 4% (2 - 7)% 10 514 6% (3 - 8)% Mid Ureter Sepsis Ureteral Injury UTI 1 37 6% (1 - 16)% 1 63 2% (0 - 7)% 5 704 3% (2 - 4)% 8 360 4% (2 - 6)% Steinstrasse 3 235 5% (2 - 10)% 1 109 0% (0 - 2)% Stricture 2 124 2% (0 - 8)% 8 987 2% (1 - 5)% Ureteral Injury 2 124 2% (0 - 8)% 10 1005 6% (3 - 9)% UTI 5 360 4% (2 - 7)% 2 224 4% (1 - 8)% Proximal Ureter Sepsis Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 28 Table 6 summarizes complications for all pediatric groups. Since there are few groups and patients, it was not possible to stratify data by stone size or location. The reported frequencies of pain may be inaccurate because of inconsistent reporting. Table 6. Complication Occurrence Rates - Overall, Pediatric Population G = number of groups/treatment arms extracted; P = number of patients in those groups. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 29 Other Surgical Interventions Small numbers of studies reported on open surgery, laparoscopic stone removal, and percutaneous antegrade ureteroscopy. Because these procedures are usually reserved for special cases, the reported data should not be used to compare procedures with each other or with SWL or URS. As expected, these more invasive procedures yielded high stone-free rates when used. A single pediatric report provided procedure counts for two patients who had one open procedure each. Two studies reported stone-free rates for children with open procedures (n=five patients); the computed stone-free rate was 82% (95% CI: 43% to 99%). The Index Patient In constructing these guidelines, an “index patient” was defined to reflect the typical individual with a ureteral stone whom a urologist treats. The following definition was created. The index patient is a nonpregnant adult with a unilateral noncystine/nonuric acid radiopaque ureteral stone without renal calculi requiring therapy whose contralateral kidney functions normally and whose medical condition, body habitus, and anatomy allow any one of the treatment options to be undertaken. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 30 Treatment Guidelines for the Index Patient For All Index Patients Standard: Patients with bacteriuria should be treated with appropriate antibiotics. [Based on Panel consensus/Level IV] Untreated bacteriuria can lead to infectious complications and possible urosepsis if combined with urinary tract obstruction, endourologic manipulation, or SWL. Urine culture prior to intervention is recommended; screening with dipsticks might be sufficient in uncomplicated cases.2 In case of suspected or proven infection, appropriate antibiotic therapy should be administered before intervention.6 Standard: Stone extraction with a basket without endoscopic visualization of the stone (blind basketing) should not be performed. [Based on Panel consensus/Level IV] Before the availability of modern ureteroscopes, extraction of distal ureteral stones with a basket with or without fluoroscopy was common. This procedure is, however, associated with an obvious risk of injury to the ureter. It is the expert opinion of the Panel that blind stone extraction with a basket should not be performed, and that intraureteral manipulations with a stone basket should always be performed under direct ureteroscopic vision. Fluoroscopic imaging of the stone alone is not sufficient. For Ureteral Stones <10 mm Option: In a patient who has a newly diagnosed ureteral stone <10 mm and whose symptoms are controlled, observation with periodic evaluation is an Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 31 option for initial treatment. Such patients may be offered an appropriate medical therapy to facilitate stone passage during the observation period. [Based on review of the data and panel opinion/Level 1A] The Panel performed a meta-analysis of studies in which spontaneous ureteral stone passage was assessed. The median probability of stone passage was 68% for stones ≤5 mm (n=224) and 47% for those >5 and ≤10 mm (n=104) in size (details previously discussed and provided in the appendixes). The Panel recognized that these studies had certain limitations including nonstandardization of the stone size measurement methods and lack of analysis of stone position, stone-passage history, and time to stone passage in some. A meta-analysis of MET was also performed which demonstrated that alpha blockers facilitate stone passage and that the positive impact of nifedipine is marginal. This analysis also indicates that alpha blockers are superior to nifedipine and, hence, may be the preferred agents for MET (details provided in the Appendixes). A similar benefit of MET was demonstrated in a recently published meta-analytic study.7 The methods of analysis used in this study were somewhat different as the absolute improvement in stone passage was calculated in our study and the relative improvement in the latter. The vast majority of the trials analyzed in this and our analysis were limited to patients with distal ureteral stones. The majority of stones pass spontaneously within four to six weeks. This was demonstrated by Miller and Kane8, who reported that of stones ≤2 mm, 2 to 4 mm and 4 to 6 mm in size, 95% of those which passed did so by 31, 40, and 39 days, respectively. In a choice between active stone removal and conservative treatment with MET, it is important to take into account all individual circumstances that may affect treatment decisions. A prerequisite for MET is that the patient is reasonably comfortable Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 32 with that therapeutic approach and that there is no obvious advantage of immediate active stone removal. Standard: Patients should be counseled on the attendant risks of MET including associated drug side effects and should be informed that it is administered for an “off label” use. [Based on Panel consensus/Level IV] Standard: Patients who elect for an attempt at spontaneous passage or MET should have well-controlled pain, no clinical evidence of sepsis, and adequate renal functional reserve. [Based on Panel consensus/Level IV] Standard: Patients should be followed with periodic imaging studies to monitor stone position and to assess for hydronephrosis. [Based on Panel consensus/Level IV] Standard: Stone removal is indicated in the presence of persistent obstruction, failure of stone progression, or in the presence of increasing or unremitting colic. [Based on Panel consensus/Level IV] For Ureteral Stones >10 mm Although patients with ureteral stones >10 mm could be observed or treated with MET, in most cases such stones will require surgical treatment. No recommendation can be made for spontaneous passage (with or without medical therapy) for patients with large stones. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 33 For Patients Requiring Stone Removal Standard: A patient must be informed about the existing active treatment modalities, including the relative benefits and risks associated with each modality. [Based on Panel consensus/Level IV] Specifically, both SWL and URS should be discussed as initial treatment options for the majority of cases. Regardless of the availability of this equipment and physician experience, this discussion should include stone-free rates, anesthesia requirements, need for additional procedures, and associated complications. Patients should be informed that URS is associated with a better chance of becoming stone free with a single procedure, but has higher complication rates. Recommendation: For patients requiring stone removal, both SWL and URS are acceptable first-line treatments. [Based on review of the data and Panel consensus/Level 1A-IV (details provided in Chapter 3)] The meta-analysis demonstrated that URS yields significantly greater stone-free rates for the majority of stone stratifications. Recommendation: Routine stenting is not recommended as part of SWL. [Based on Panel consensus/Level III] The 1997 AUA guideline, Report on the Management of Ureteral Calculi, stated that “Routine stenting is not recommended as part of SWL.”9 The 1997 guideline Panel noted that it had become common practice to place a ureteral stent for more efficient fragmentation of ureteral stones when using SWL. However, the data analyzed showed Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 34 no improved fragmentation with stenting.9 The current analysis demonstrates similar findings. In addition, studies assessing the efficacy of SWL treatment with or without internal stent placement have consistently noted frequent symptoms related to stents.10-13 Option: Stenting following uncomplicated URS is optional. [Based on Panel consensus/Level 1A] Several randomized prospective studies published since the 1997 AUA guideline document have demonstrated that routine stenting after uncomplicated URS may not be necessary.10, 14-19 It is well documented that ureteral stenting is associated with bothersome lower urinary tract symptoms and pain that can, albeit temporarily, alter quality of life.15-17, 20-26 In addition, there are complications associated with ureteral stenting, including stent migration, urinary tract infection, breakage, encrustation, and obstruction. Moreover, ureteral stents add some expense to the overall ureteroscopic procedure and unless a pull string is attached to the distal end of the stent, secondary cystoscopy is required for stent removal.27 There are clear indications for stenting after the completion of URS. These include ureteral injury, stricture, solitary kidney, renal insufficiency, or a large residual stone burden. Option: Percutaneous antegrade ureteroscopy is an acceptable first-line treatment in select cases. [Based on Panel consensus/Level III] Instead of a retrograde endoscopic approach to the ureteral stone, percutaneous antegrade access can be substituted.28 This treatment option is indicated: • in select cases with large impacted stones in the upper ureter Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 35 • in combination with renal stone removal • in cases of ureteral stones after urinary diversion29 • in select cases resulting from failure of retrograde ureteral access to large, impacted upper ureteral stones.30 Option: Laparoscopic or open surgical stone removal may be considered in rare cases where SWL, URS, and percutaneous URS fail or are unlikely to be successful. [Based on Panel consensus/Level III] The 1997 AUA guideline stated that “Open surgery should not be the first-line treatment.”9 The invasiveness and morbidity of open surgery can be avoided. In very difficult situations, however, such as with very large, impacted stones and/or multiple ureteral stones, or in cases of concurrent conditions requiring surgery, an alternative procedure might be desired as primary or salvage therapy. Laparoscopic ureterolithotomy is a less invasive alternative to open surgery in this setting. Comparative series indicate that open surgical ureterolithotomy can be replaced by laparoscopic ureterolithotomy in most situations.31, 32 From the 15 case series of laparoscopic ureterolithotomy included in the Panel’s literature review, the median stone-free rate was 88% for the primary treatment. It is notable that this success was achieved when virtually all of the procedures were for large and/or impacted calculi. Recommendations for the Pediatric Patient Option: Both SWL and URS are effective in this population. Treatment choices should be based on the child’s size and urinary tract anatomy. The Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 36 small size of the pediatric ureter and urethra favors the less invasive approach of SWL. [Based on review of data and Panel consensus/Level III] Recommendations for the Nonindex Patient Standard: For septic patients with obstructing stones, urgent decompression of the collecting system with either percutaneous drainage or ureteral stenting is indicated. Definitive treatment of the stone should be delayed until sepsis is resolved. [Based on Panel consensus/Level III] The compromised delivery of antibiotics into the obstructed kidney mandates that the collecting system be drained to promote resolution of the infection. The choice of drainage modality, whether percutaneous nephrostomy or ureteral stent, is left to the discretion of the urologist, as both have been shown in a randomized trial to be equally effective in the setting of presumed obstructive pyelonephritis/pyonephrosis.33 Definitive treatment of the stone should be delayed until sepsis has resolved and the infection is cleared following a complete course of appropriate antimicrobial therapy. Discussion There are two significant changes in treatment approach that distinguish the present document from the guideline published by the AUA in 1997. The most significant change is the use of retrograde URS as first-line treatment for middle and upper ureteral stones with a low probability of spontaneous passage. This change reflects Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 37 both the vast technological improvements that have been made during the last decade and the experience and facility that surgeons now have with the procedure. The other change is the establishment of effective MET to facilitate spontaneous stone passage. These advances, the current status of other technologies and procedures, issues related to nonindex patients, and future directions and research germane to this condition will be subsequently discussed. Medical Expulsive Therapy There is growing evidence that MET, the administration of drugs to facilitate stone passage, can be efficacious. Studies have demonstrated that this approach may facilitate and accelerate the spontaneous passage of ureteral stones as well as stone fragments generated with SWL.34-38 Our meta-analysis demonstrated the effectiveness of MET. Nine percent (CI: -7% to 25%) more patients receiving nifedipine passed their stones than did controls in our meta-analysis, a difference that was not statistically significant. In contrast, a statistically significant 29% (CI: 20% to 37%) more patients passed their stones with alpha blocker therapy than did control patients. These findings indicate that alpha blockers facilitate ureteral stone passage while nifedipine may provide a marginal benefit. Therefore, the Panel feels that alpha blockers are the preferred agents for MET at this time. Similar findings have been reported by Hollingsworth and associates7, who recently performed a meta-analysis of studies involving alpha blockers or nifedipine in patients with ureteral stones. The differences in methodology from our study have been previously mentioned. Patients given either one of these agents had a greater likelihood of stone passage than those not receiving such therapy. The pooled-risk ratios and 95% CIs for alpha blockers and calcium channel blockers were 1.54 (1.29 to Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 38 1.85) and 1.90 (1.51 to 2.40).7 The benefit of adding corticosteroids was reported to be small.7, 37 Tamsulosin has been the most common alpha blocker utilized in these studies. However, one small study demonstrated tamsulosin, terazosin, and doxazosin as equally effective in this setting.39 These studies also demonstrated that MET reduces the stonepassage time and limits pain. The beneficial effects of these drugs are likely attributed to ureteral smooth muscle relaxation mediated through either inhibition of calcium channel pumps or alpha-1 receptor blockade. Further prospective and randomized studies are warranted to determine the patients who best respond to MET. A large, multicenter, randomized, placebo-controlled study has recently been funded in the United States for this purpose. Patients with ureteral stones in all segments of the ureter will be randomized to tamsulosin or placebo. Shock-wave Lithotripsy Shock-wave lithotripsy was introduced to clinical practice as a treatment for ureteral stones in the early 1980s. Today, even with the refinement of endourologic methods for stone removal such as URS and PNL, SWL remains the primary treatment for most uncomplicated upper urinary tract calculi. The meta-analysis published by the AUA Nephrolithiasis Guideline Panel in 1997 documented that the stone-free rate for SWL for proximal ureteral stones overall was 83% (78 studies, 17,742 patients). To achieve this result, 1.40 procedures were necessary per patient. The results were very similar in the distal ureter, with a stone-free rate of 85% (66 studies, 9,422 patients) necessitating 1.29 primary and secondary procedures per patient. There was no significant difference between various SWL techniques (SWL with pushback, SWL with Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 39 stent or catheter bypass, or SWL in situ). Consequently, the Panel suggested that the use of a ureteral stent to improve stone-free rates was not warranted. This observation is also confirmed by the present analysis. However, there may be circumstances such as when the stone is small or of low radiographic density where a stent or ureteral catheter (sometimes using a contrast agent) may help facilitate localization during SWL. The Panel considered complications of SWL for ureteral stones to be infrequent. The current meta-analysis analyzed SWL stone-free results for three locations in the ureter (proximal, mid, distal). The SWL stone-free results are 82% in the proximal ureter (41 studies, 6,428 patients), 73% in the mid ureter (31 studies, 1,607 patients), and 74% in the distal ureter (50 studies, 6,981 patients). The results in the 1997 guideline, which divided the ureter into proximal and distal only, reported SWL stone-free results of 83% and 85%, respectively. The CIs for the distal ureter do not overlap and indicate a statistically significant worsening of results in the distal ureter from the earlier results. No change is shown for the proximal ureter. The cause of this difference is not clear. Additional procedures also were infrequently necessary (0.62 procedures per patient for proximal ureteral stones, 0.52 for mid-ureteral stones, and 0.37 for distal ureteral stones). Serious complications were again infrequent. As expected, stone-free rates were lower and the number of procedures necessary were higher for ureteral stones >10 mm in diameter managed with SWL. The outcomes for SWL for ureteral calculi in pediatric patients were similar to those for adults, making this a useful option, particularly in patients where the size of the patient (and ureter/urethra) may make URS a less attractive option. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 40 The newer generation lithotriptors with higher peak pressures and smaller focal zones should, in theory, be ideal for the treatment of stones in the ureter but instead have not been associated with an improvement in stone-free rates or a reduction in the number of procedures needed when this treatment approach is chosen. In fact, the SWL stone-free rates for stones in the distal ureter have declined significantly when compared with the 1997 AUA analysis. The explanation for the lack of improvement in SWL outcomes is unknown. Although ureteroscopic stone removal is possible with intravenous sedation, one clear advantage of SWL over URS is that the procedure is more easily and routinely performed with intravenous sedation or other minimal anesthetic techniques. Therefore, for the patient who desires treatment with minimal anesthesia, SWL is an attractive approach. Shock-wave lithotripsy can be performed with the aid of either fluoroscopy or ultrasound (US). While some stones in the proximal and distal ureter can be imaged with US, this imaging modality clearly limits SWL application in the ureter when compared to fluoroscopy. However, a combination of both fluoroscopy and US can facilitate stone location and minimize radiation exposure. As documented in the 1997 AUA report, there appears to be little, if any, advantage to routine stenting when performing SWL for ureteral stones. Concerns have been raised, too, regarding the use of SWL to treat distal ureteral calculi in women of childbearing age because of the theoretical possibility that unfertilized eggs and/or ovaries may be damaged. To date, no objective evidence has been discovered to support such concerns, but many centers require that women age 40 or Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 41 younger be fully informed of the possibility and give their consent before treatment with SWL.40-44 Ureteroscopy Ureteroscopy has traditionally constituted the favored approach for the surgical treatment of mid and distal ureteral stones while SWL has been preferred for the less accessible proximal ureteral stones. With the development of smaller caliber semirigid and flexible ureteroscopes and the introduction of improved instrumentation, including the holmium:YAG laser, URS has evolved into a safer and more efficacious modality for treatment of stones in all locations in the ureter with increasing experience worldwide.45, 46 Complication rates, most notably ureteral perforation rates, have been reduced to less than 5%, and long-term complications such as stricture formation occur with an incidence of 2% or less.47 Overall stone-free rates are remarkably high at 81% to 94% depending on stone location, with the vast majority of patients rendered stone free in a single procedure (Figure 1 and Chapter 3). In 1997, the AUA Nephrolithiasis Clinical Guideline Panel recommended SWL for <1 cm stones in the proximal ureter and either SWL or URS for >1 cm proximal ureteral stones.9 With improved efficacy and reduced morbidity currently associated with ureteroscopic management of proximal ureteral stones, this modality is now deemed appropriate for stones of any size in the proximal ureter. Indeed, the current analysis revealed a stone-free rate of 81% for ureteroscopic treatment of proximal ureteral stones, with surprisingly little difference in stone-free rates according to stone size (93% for stones <10 mm and 87% for stones >10 mm). The flexible ureteroscope is largely Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 42 responsible for improved access to the proximal ureter; superior stone-free rates are achieved using flexible URS (87%) compared with rigid or semirigid URS (77%). These stone-free rates are comparable to those achieved with SWL. The middle ureter poses challenges for all surgical stone treatments; the location over the iliac vessels may hinder access with a semirigid ureteroscope, and identification and targeting of mid-ureteral stones for SWL has proved problematic due to the underlying bone. Despite the limitations, ureteroscopic management is still highly successful; a stone-free rate of 86% was demonstrated in the current analysis, although success rates declined substantially when treating larger stones (>10 mm) compared with smaller stones (78% versus 91%, respectively). Ureteroscopic treatment of distal ureteral stones is uniformly associated with high success rates and low complication rates. An overall stone-free rate of 94% was achieved with either a rigid or semirigid ureteroscope, with little drop off in stone-free rates when treating larger stones. On the other hand, flexible URS was less successful than rigid or semirigid URS for distal ureteral stones, particularly those >10 mm, likely due to difficulty maintaining access within the distal ureter with a flexible ureteroscope. A number of adjunctive measures have contributed to the enhanced success of ureteroscopic management of ureteral calculi. Historically, stones in the proximal ureter have been associated with lower success rates than those in the mid and distal ureter, in part because the proximal ureter is more difficult to access and stone fragments often become displaced into the kidney where they may be difficult to treat. Improved flexible ureteroscopes and greater technical skill, along with the introduction of devices to Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 43 prevent stone migration48, 49 have improved the success of treating proximal ureteral stones. Although the efficacy of URS for the treatment of ureteral calculi has been amply shown, the need for a ureteral stent with its attendant morbidity has biased opinion towards SWL in some cases. Clearly, SWL is associated with fewer postoperative symptoms and better patient acceptance than URS. However, a number of recent prospective, randomized trials have shown that for uncomplicated URS, the ureter may be left unstented without undue risk of obstruction or colic requiring emergent medical attention.10, 14-19 Ureteroscopy can also be applied when SWL might be contraindicated or illadvised. Ureteroscopy can be performed safely in select patients in whom cessation of anticoagulants is considered unsafe.50 In addition, URS has been shown to be effective regardless of patient body habitus. Several studies have shown that morbidly obese patients can be treated with success rates and complication rates comparable to the general population.51, 52 Finally, URS can be used to safely simultaneously treat bilateral ureteral stones in select cases.53-55 Percutaneous Antegrade Ureteroscopy Percutaneous antegrade removal of ureteral stones is a consideration in selected cases, for example, for the treatment of very large (>15 mm diameter) impacted stones in the proximal ureter between the ureteropelvic junction and the lower border of the fourth lumbar vertebra.30, 56 In these cases with stone-free rates between 85% and 100%, its superiority to standard techniques has been evaluated in one prospective randomized57 and in two prospective studies.28, 30 In a total number of 204 patients, the complication Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 44 rate was low, acceptable, and not specifically different from any other percutaneous procedure. Percutaneous antegrade removal of ureteral stones is an alternative when SWL is not indicated or has failed58 and when the upper urinary tract is not amenable to retrograde URS; for example, in those with urinary diversion29 or renal transplants.59 Laparoscopic and Open Stone Surgery Shock-wave lithotripsy, URS, and percutaneous antegrade URS can achieve success for the vast majority of stone cases. In extreme situations or in cases of simultaneous open surgery for another purpose, open surgical ureterolithotomy might rarely be considered.60, 61 For most cases with very large, impacted, and/or multiple ureteral stones in which SWL and URS have either failed or are unlikely to succeed, laparoscopic ureterolithotomy is a better alternative than open surgery if expertise in laparoscopic techniques is available. Both retroperitoneal and transperitoneal laparoscopic access to all portions of the ureter have been reported. Laparoscopic ureterolithotomy in the distal ureter is somewhat less successful than in the middle and proximal ureter, but the size of the stone does not appear to influence outcome. Although highly effective, laparoscopic ureterolithotomy is not a first-line therapy in most cases because of its invasiveness, attendant longer recovery time, and the greater risk of associated complications compared to SWL and URS. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 45 Special Considerations Pregnancy Renal colic is the most common nonobstetric cause of abdominal pain in pregnant patients requiring hospitalization. The evaluation of pregnant patients suspected of having renal colic begins with ultrasonography, as ionizing radiation should be limited in this setting. If the US examination is unrevealing and the patient remains severely symptomatic, a limited intravenous pyelogram may be considered. A typical regimen includes a preliminary plain radiograph (KUB) and two films, 15 minutes and 60 minutes following contrast administration. Noncontrast computed tomography is uncommonly performed in this setting because of the higher dose of radiation exposure. Magnetic resonance imaging can define the level of obstruction, and a stone may be seen as a filling defect. However, these findings are nonspecific. In addition, there is a paucity of experience with using this imaging modality during pregnancy.62 Once the diagnosis has been established, these patients have traditionally been managed with temporizing therapies (ureteral stenting, percutaneous nephrostomy), an approach often associated with poor patient tolerance. Further, the temporizing approach typically requires multiple exchanges of stents or nephrostomy tubes during the remainder of the patient's pregnancy due to the potential for rapid encrustation of these devices. A number of groups have now reported successful outcomes with URS in pregnant patients harboring ureteral stones. The first substantial report was by Ulvik, et al63 who reported on the performance of URS in 24 pregnant women. Most patients had stones or edema, and there were no adverse sequelae associated with ureteroscopic stone Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 46 removal. Similar results have been reported by Lifshitz and Lingeman64 and Watterson et al65 who found that the ureteroscopic approach was both diagnostic and therapeutic in pregnant patients with very low morbidity and the need for only short-term ureteral stenting, if at all, afterwards. When intracorporeal lithotripsy is necessary during ureteroscopic treatment of calculi in pregnant patients, the holmium laser has the advantage of minimal tissue penetration, thereby theoretically limiting risk of fetal injury. Pediatrics Both SWL and URS are effective treatment alternatives for stone removal in children. Selection of the most appropriate treatment has to be based on the individual stone problem, the available equipment and the urologist’s expertise in treating children. Children appear to pass stone fragments after SWL more readily than adults.66-71 Ureteroscopy may be used as a primary treatment or as a secondary treatment after SWL in case of poor stone disintegration. Less efficient SWL disintegration might be seen in children with stones composed of cystine, brushite and calcium oxalate monohydrate or when anatomic abnormalities result in difficulties in fluoroscopic or ultrasonographic visualization of the stone.72-74 One of the main problems with pediatric URS is the size of the ureteroscope relative to the narrow intramural ureter and the urethral diameter. This problem has lately been circumvented by the use of smaller ureteroscopes, for example, mini or needle instruments as well as small flexible semirigid or rigid ureteroscopes and pediatric (6.9 Fr) cystoscopes. With the availability of 4.5 and 6.0 Fr semirigid ureteroscopes, a 5.3 Fr flexible ureteroscope and a holmium:YAG laser energy source, instrument-related complications have become uncommon.73-75 However, the utilization of proper technique Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 47 remains the most important factor for generating successful outcomes in this population. Percutaneous stone removal is also possible in pediatric patients with comparable indications to those in adults. Such an approach might be considered for stone removal in children with a malformation of the lower urinary tract. Cystine Stones Individuals with cystinuria are considered nonindex patients by the Panel for a variety of reasons. There are limited data regarding treatment outcomes in this group.76-83 In vitro studies also show that these stones are commonly resistant to SWL, although the degree of resistance may be variable.77, 78 The structural characteristics of these stones are thought to contribute to their decreased SWL fragility. In addition, some of these stones may be barely opaque on standard imaging or fluoroscopy, potentially compromising shock-wave focusing. In contrast to SWL, technology currently utilized for intracorporeal lithotripsy during URS, including the holmium laser, ultrasonic and pneumatic devices, can readily fragment cystine stones.81 Certain imaging characteristics may predict SWL outcomes for this patient group. Bhatta and colleagues reported that cystine stones having a rough-appearing external surface on plain film imaging were more apt to be fragmented with shock-wave energy than those with a smooth contour.82 Kim and associates reported that the computed tomography attenuation coefficients of the latter were significantly higher than the roughtype stones.83 Other types of stones with higher attenuation values have also been demonstrated to be resistant to shock-wave fragmentation.84 Patients with this rare genetic disorder typically have their first stone event early in life, are prone to recurrent stones, and are consequently subject to repetitive removal Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 48 procedures. In addition, patients with cystinuria are at risk for developing renal insufficiency over time.85, 86 Prophylactic medical therapy and close follow-up can limit recurrence. Uric acid Stones Uric acid calculi are typically radiolucent, thus limiting the ability to treat such patients using in situ SWL. However, this approach may be possible with devices that use US if the stone can indeed be localized. When properly targeted, these stones fragment readily with SWL. Uric acid stones have lower computed tomography attenuation values, and can usually can be distinguished from calcium, cystine, and struvite calculi.87 The presence of a low attenuation or a radiolucent stone, particularly in a patient with a low urinary pH, should lead the clinician to suspect this diagnosis. Manipulation of the urinary pH with oral potassium citrate, sodium citrate, or sodium bicarbonate to a level ranging from 6.0 to 7.0 may obviate the need for surgical intervention. Moreover, this medical treatment may allow stone dissolution in patients whose symptoms are controllable, should prevent the development of future uric acid stones, and has also been shown to enhance stone clearance with SWL.88 Medical expulsive therapy may be administered concomitantly. Ureteroscopy is a very effective method of treating patients who are not candidates for observation.89 Research and Future Directions Ten years have elapsed since the last publication of the AUA guidelines, and one year since the EAU recommendations on ureteral stones. Extensive cooperation between AUA and EAU Panel members has produced this unique collaborative report. This Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 49 venture should provide the foundation for future collaborative efforts in guideline development. The Panel encountered a number of deficits in the literature. While the management of ureteral stones remains commonly needed, few RCTs were available for data extraction. The data were inconsistent, starting from the definition of stone sizes and ending with variable definitions of a stone-free state. These limitations hinder the development of evidence-based recommendations. To improve the quality of research, the Panel strongly recommends the following: • conducting RCTs comparing interventional techniques like URS and SWL • conducting pharmacological studies of stone-expulsion therapies as doubleblinded RCTs • reporting stone-free data without inclusion of residual fragments • using consistent nomenclature to report stone size, stone location, stone-free rates, time point when stone-free rate is determined, or method of imaging to determine stone-free rate • reporting data stratified by patient/stone characteristics, such as patient age, stone size, stone location, stone composition, gender, body mass index, and treatment modality • reporting all associated treatments including placement of ureteral stents or nephrostomies • using standardized methods to report acute and long-term outcomes • developing methods to predict outcomes for SWL, URS, and MET Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 50 • providing measures of variability such as standard deviation, standard error, CI, or variance with corresponding average patient numbers • reporting raw data to facilitate meta-analyses The Panel suggests focusing on the following issues in future investigations: • investigating the proposed current efficacy problems of second and third generation shock-wave machines and developing approaches to improve SWL • determining the safety of each technique with respect to acute and long-term effects • investigating the promising medical stone expulsion in basic research studies and in clinical trials to unravel the underlying mechanisms and to optimize the treatment regimens • addressing issues such as patient preferences, quality of life, and time until the patient completed therapy when evaluating treatment strategies. To date, only a few studies have addressed patient preference.90-92 • although largely dependent on different health systems, addressing costeffectiveness Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 51 Chapter 2: Methodology Table of Contents Introduction..................................................................................................................................... 2 Problem Definition.......................................................................................................................... 2 Literature Search and Data Extraction............................................................................................ 3 Evidence Combination.................................................................................................................... 4 Stone-free Analysis..................................................................................................................... 7 Procedures per Patient ................................................................................................................ 8 Complications ............................................................................................................................. 8 Analyses of Data from Adults and Children............................................................................... 9 Guideline Generation and Approvals............................................................................................ 10 Dissemination ............................................................................................................................... 10 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 1 Introduction This guideline was developed using an explicit approach to address the relevant factors for choosing among alternative interventions. These factors include outcomes of the interventions, patient preferences, and the relative priorities of interventions given limited health care resources. The guideline Panel used scientific evidence to estimate outcomes of treatment modalities as accurately as possible. Panel members themselves served as proxies for patients in considering preferences with regard to health and economic outcomes. The steps taken to develop this guideline are summarized in Chapter 1 and described in detail in the present Chapter. Steps included problem definition, literature search, data extraction, systematic evidence combination, guideline generation, approval, and dissemination. Problem Definition This guideline was the first joint guideline effort of the American Urological Association (AUA) and the European Association of Urology (EAU). Initial discussions included methodology and the scope of the guideline. It was decided that the methodology for problem definition, data collection, and initial analysis would be similar to that used in the previous AUA guideline. All treatments commonly performed in the United States and/or Europe were included in this update except for treatments that were explicitly excluded in the previous guideline or newer treatments for which insufficient literature exists. The Panel initially desired to stratify patient data by age (adult versus child), stone size, stone location, and stone composition. Later, however, the data were found to be insufficient to allow analysis by composition. The outcomes deemed by the Panel to be of particular interest to the patient included stone-free rate, number of procedures performed, stone-passage rate or probability of Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 2 spontaneous passage, and complications of treatment. The Panel did not examine economic effects, including treatment costs. Outcomes were stratified by stone location (proximal, mid, and distal ureter) and by stone size (dichotomized as ≤10 mm and >10 mm for surgical interventions, and ≤5 mm and >5 mm for medical interventions and observation where possible; exceptions were made when data were reported, for example as <10 mm and ≥10 mm). The mid ureter is the part of the ureter that overlies the bony pelvis, i.e., the position of the ureter that corresponds to the sacroiliac joint; the proximal ureter is above and the distal ureter is below. Treatments were divided into three broad groups: 1. Observation and medical therapy 2. Shock-wave lithotripsy and ureteroscopy 3. Open surgery, laparoscopic stone removal, or percutaneous antegrade ureteroscopy. Literature Search and Data Extraction The review of the evidence began with a literature search and data extraction. Articles were selected from a database of papers derived from MEDLINE searches dealing with all forms of urinary tract stones. This database was maintained by a Panel chair. The abstract of each paper was independently reviewed by an American and a European Panel member, and articles were selected for data extraction if any panel member felt it might have useful data. Additional articles were suggested by Panel members or found as references in review articles. In total, 348 citations entered the extraction process. An American and a European Panel member each independently extracted data from each article onto a standardized form (Appendix 5). The team members reconciled the extractions, and the data were entered into a Microsoft Access® Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 3 (Microsoft, Redmond, WA) database. The Panel scrutinized the entries, reconciled the inconsistencies in recording, corrected the extraction errors, and excluded some articles from further analysis for the following reasons: 1. The article was included in the previous guideline. 2. The article did not provide usable data on the outcomes of interest. 3. Results for patients with ureteral stones could not be separated from results for those with renal stones. 4. The treatments used were not current or were not the focus of the analysis. 5. The article was a review article of data reported elsewhere. 6. The article dealt only with salvage therapy. A total of 244 of the articles were initially accepted, although some were later rejected from inclusion in both the efficacy and complications analyses. For example, some articles were not included in the efficacy analysis but were included in the safety analysis for certain complications in which there was clarity as far as reported data. A complete list of these articles is presented in both Appendix 6, ordered by primary author, and Appendix 7, ordered by reference number. Articles excluded from evidence combination remained candidates as references to support the discussion in the text of the Guideline. Evidence Combination The analytic goal was to generate outcome tables comparing estimates of outcomes across treatment modalities. To generate an outcome table, estimates of the probabilities and/or magnitudes of the outcomes are required for each intervention. Ideally, these are derived from a synthesis or combination of the evidence. Such a combination can be performed in a variety of Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 4 ways depending on the nature and quality of the evidence. For example, if there is one wellconducted randomized controlled trial, the results of that trial alone may be used in the outcomes table while findings of other studies of lesser quality are ignored. Alternatively, if there are no studies of satisfactory quality for certain outcomes tables or if available studies are not commensurable, expert opinion may be used to complete the table. Finally, if a number of studies have some degree of relevance to a particular outcome or outcomes, then meta-analytic mathematical methods may be used. A variety of specific meta-analytic methods are available, and selection of a particular method depends on the nature of the evidence. For this 2007 Guideline for the Management of Ureteral Calculi, the Panel elected to use the Confidence Profile Method, which provides methods for analyzing data from studies that are not randomized controlled trials. The Fast*Pro computer software was used in the analysis. This program provides posterior distributions from meta-analyses from which the median can be used as a best estimate, and the central 95% of the distribution serves as a confidence interval. Statistical significance at the p<0.05 level (twotailed) was inferred when zero was not included in the confidence interval. Because of the paucity of controlled trials found on literature review, however, the outcome for each intervention was estimated by combining single arms from various clinical series. These clinical series frequently had very different outcomes, likely due to a combination of site-to-site variations in patient populations, in the performance of the intervention, in the skill of those performing the intervention, and different methods of determining stone-free status. Given these differences, a random-effects, or hierarchical, model was used to combine the studies. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 5 A random-effects model assumes that there is an underlying true rate for the outcome being assessed for each site. It further assumes that this underlying rate varies from site to site. This site-to-site variation in the true rate is assumed to be normally distributed. The method of meta-analysis used attempts to determine these underlying distributions. The results of the confidence-profile method are probability distributions that are described using the median of the distribution with a confidence interval. In this case, the 95% confidence interval indicates that the probability (Bayesian) of the true value being outside the interval is 5%. These Bayesian confidence intervals are sometimes called credible intervals. The Bayseian method of computation assumes a “prior” distribution that reflects knowledge about the probability of the outcome before the results of any experiments are known. The prior distributions selected for this analysis are among a class of “noninformative” prior distributions, which means that they correspond to little or no prior knowledge. The existence of such a prior distribution can cause small changes in results, particularly for small studies. The prior distribution for all probability parameters is Jefferey’s prior (beta distribution with both parameters set to 0.5). The prior for the variance for the underlying normal distribution is gamma distributed with both parameters set to 0.5. Three of the four outcomes identified as important to patients receiving treatment for ureteral calculi were analyzed using these methods; insufficient data were available to use these techniques for the outcome procedures per patient. Evidence from the studies meeting the inclusion criteria and reporting a given outcome was combined within each treatment modality. Graphs showing the results for each modality were developed to demonstrate similarities and differences between treatments. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 6 It is important to note that for certain outcomes more data were reported for one or another treatment modality. While resulting confidence intervals reflect available data, the probabilities for certain outcomes can vary widely from study to study within one treatment modality. In addition, the fact that data from only a few randomized controlled trials could be evaluated may have somewhat biased results. For example, differences in patient selection may have had more weight in analyses than differing treatment effects. Nevertheless, the results obtained reflect the best outcome estimates presently available. Stone-free Analysis Studies that reported numbers of patients who were stone free after primary procedures were included in the stone-free analysis. Studies that reported only the combined number of patients who either were stone free or had “clinically insignificant fragments” were excluded. Many studies did not indicate how or when stone-free status was determined. The stone-free rate was considered at three time points: after the first procedure, after all consecutive procedures using the primary treatment, and after total treatments. After considering the data and the way they were reported, the Panel ultimately decided to report only a single number. That number would be based on the stone-free rate after all consecutive primary treatments if available for a given group of patients within an article. If not, then the number would be based on the number of patients stone free after the first primary treatment. If only the total stone-free rate was available, it would not be used. The Panel elected to use this method since the ultimate total stone-free rate is expected to be nearly always 100 % in subjects with ureteral stones. The procedure count data could be used to show how many primary procedures, on average, would be needed to get the stone-free rate reported. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 7 Procedures per Patient Unlike the binary outcome of stone-free status (the patient either is or is not stone free), the number of procedures per patient is a discrete rate. In some cases, discrete rates can be approximated with a continuous rate, but in order to meta-analyze continuous rates, a measure of variance (e.g., standard deviation, standard error) is needed in addition to the mean. Unfortunately, measures of variance were rarely reported in the studies reviewed. As a result, numbers of procedures per patient were evaluated by calculating the average across studies weighted by the number of patients in each study. Procedures per patient were counted in three totals: primary procedures, secondary procedures, and adjunctive procedures. Primary procedures were all consecutive procedures of the same type aimed at removing the stone. Secondary procedures were all other procedures used to remove the stone. Adjunctive procedures were defined as additional procedures that do not involve active stone removal. One difficulty in estimating the total number of procedures per patient is that secondary and adjunctive procedures were not reported consistently. Some studies reported secondary and adjunctive procedures together as the “extra” procedures performed beyond the primary procedure. Other studies reported only primary procedures, while others simply provided an undefined total number of procedures. Since the Panel had decided to analyze primary, secondary, and adjunctive procedures separately, only studies that specifically reported data on a type of procedure were included in estimates for that procedure type. This approach may have overestimated numbers of secondary and adjunctive procedures because some articles may not have reported that procedures were not performed. Complications Initially, the Panel divided complications into three broad categories: acute, long-term, and medical; however, after examining the available evidence, the Panel determined that this Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 8 breakdown was not useful. Complications were variably reported and only studies that specifically reported data concerning occurrences of complications were included in the analysis. Transfusions and a composite category of all other acute complications were meta-analyzed. Several factors caused inaccuracy in the estimates, but did so in opposite directions, thereby reducing the magnitude of the inaccuracy. For example, including studies that did not specifically mention that there were no occurrences of a specific complication may have led to overestimates of complication rates when meta-analyzed. By combining similar complications, the Panel also potentially mitigated the overestimate by making it more likely that a complication in the class was reported. The probability that a patient will have a complication may still be overstated slightly because some patients experience multiple complications. Since the grouping of complications varies by study, the result of the meta-analysis is best interpreted as the mean number of complications that a patient may experience rather than as the probability of having a complication. Moreover, since reporting of complications is not consistent, the estimated rates given here are probably less accurate than the confidence intervals would indicate. There were insufficient data to permit meaningful meta-analyses of patient deaths. The estimates of death rates provided in the guideline are the Panel's expert opinion based on the limited data available. Analyses of Data from Adults and Children Data analyses were conducted for two age groups. One analysis included studies of patients age 18 or younger (or identified as pediatric patients in the article without specifying age ranges). A separate adult analysis was rejected since many studies included both adults and children or weren’t clear about whether children were included. An overall analysis was done which included all studies including those including children. This overall analysis is primarily adult patients. The Panel considered the number of children in these cases to be too small to significantly influence the results. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 9 Guideline Generation and Approvals After the evidence was combined and outcome tables were produced, the Panel met to review the results and identify anomalies. Additional teleconferences were held to review updates to the outcomes tables based on the problems identified. From the evidence in the outcome tables and expert opinion, the Panel drafted the treatment guideline. The draft was sent to 81 peer reviewers of whom 26 provided comments; the Panel revised the document based on the comments received. The guideline was submitted first for approval to the Practice Guidelines Committee of the AUA and the Guidelines Office of the EAU and then forwarded to the AUA Board of Directors and the EAU Board for final approval. Dissemination The guideline is posted on the American Urological Association website, www.auanet.org, and on the European Association of Urology website, www.uroweb.org. Chapter 1 will be published in The Journal of Urology and in European Urology. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 10 Chapter 3: Outcomes Analysis for the Management of Ureteral Calculi Table of Contents Introduction........................................................................................................................................2 Observation and Medical Therapies ..................................................................................................3 Shock-wave Lithotripsy and Ureteroscopy........................................................................................5 Efficacy Outcomes .......................................................................................................... 6 Stone-free rates............................................................................................................ 6 Procedure counts ....................................................................................................... 13 Complications and Side Effects .................................................................................... 21 Other Surgical Interventions ............................................................................................................36 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 1 Introduction The underlying purpose of data extraction from the literature by the Panel was to develop estimates of the outcomes of interest to the patient for each of the relevant treatments. The data were meta-analyzed to yield estimates of these outcomes. Where possible and relevant, attempts also were made to determine whether differences among treatments reached statistical significance. The results of the analysis described in this chapter provide most of the evidentiary basis for the guideline statements in Chapter 1. Relevant treatments may vary depending on the patient’s general condition and the size, location, and composition of the stone. The Panel initially intended to produce outcomes tables stratified by each of these variables. However, lack of sufficiently stratified data constrained the analysis, and outcomes were stratified only by stone location (proximal, mid, and distal ureter) and by stone size (dichotomized as ≤10 mm and >10 mm for surgical interventions and ≤5 mm and >5 mm for medical interventions and observation where possible; exceptions were made when data were reported, for example, as <10 mm and ≥10 mm). The mid ureter is the part of the ureter that overlies the bony pelvis, i.e., the position of the ureter that corresponds to the sacroiliac joint; the proximal ureter is above and the distal ureter is below. Treatments were divided into three broad groups: 1. Observation and medical therapy – primarily for patients with smaller stones 2. Shock-wave lithotripsy (SWL) and ureteroscopy (URS) – for patients with larger stones Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 2 3. Open surgery, laparoscopic stone removal, or percutaneous antegrade ureteroscopy – for patients who are not candidates for URS or SWL or who have failed those treatments Studies reporting these interventions did not always clearly indicate patient differences in stone size, location, and composition or segregate patients to treatments based on those differences. As a result, the findings presented are not based on cleanly delineated patient groups. Nevertheless, the results represent the Panel’s best estimates based on available data. The Panel’s attempt to segregate results for pediatric patients from those for adults was not completely successful as most studies included both adults and children. Where possible, the Panel performed two analyses, one including all studies regardless of patient age, and a second including only those studies or groups of patients that were comprised entirely of pediatric patients. The latter analysis was not possible for observation/medical therapies due to a lack of data. Observation and Medical Therapies Most small stones and many larger stones pass spontaneously. The Panel attempted to estimate from the literature the probability of spontaneous passage by stone size, but only limited data were found. For stones ≤5 mm, meta-analysis of five patient groups (224 patients) yielded an estimate that 68% would pass spontaneously (95% confidence interval [CI]: 46% to 85%). For stones >5 mm and ≤10 mm, analysis of three groups (104 patients) yielded an estimate that 47% would pass spontaneously (95% CI: 36% to 59%). Details of the meta-analysis are presented in Appendix 8. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 3 Analysis of medical therapies was complicated by the fact that treatments were not standardized and control groups, where present, may or may not have received steroids or other therapies. Two medical therapies had sufficient analyzable data: nifedipine and alpha-1 adrenergic blockers. Analysis of stone-passage rates were done in three ways. The first combined all single arms evaluating the therapies. Using this approach, meta-analysis of four studies of nifedipine (160 patients) yielded an estimate of a 75% passage rate (95% CI: 63% to 84%). Six studies examined alpha blockers (280 patients); the meta-analysis yielded a stone-passage rate of 81% (95% CI: 72% to 88%). One study compared three alpha blockers (tamsulosin, terazosin, and doxazosin) and found no differences in passage rates among them (ref 18204). The second method was a standard Bayesian hierarchical meta-analysis of available randomized controlled trials (RCTs) that compared either nifedipine or alpha blockers to control therapy. The results for nifedipine showed an absolute increase of 8% in stone-passage rates (95% CI: -7% to 25%) which was not statistically significant. Meta-analysis of alpha blockers versus control showed an absolute increase of 29% in the stone-passage rate (95% CI: 20% to 37%) which was statistically significant. The Panel also attempted to determine whether alpha blockers provide superior stone passage when compared to nifedipine. Two randomized controlled trials were identified. When hierarchical meta-analysis was performed on these two studies, tamsulosin provided an absolute increase in stone-passage rate of 14% (95% CI: -4% to 32%) which was not statistically significant. When nonhierarchical methods were used, the stone-passage improvement increased to 16% (95% CI: 7% to 26%) which was statistically significant. Finally, the Panel used the results of the meta-analyses versus Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 4 controls (second method above) to determine the difference between alpha blockers and calcium channel blockers. This method allows the use of more data but is risky since it depends on the control groups having comparable results. The analysis yielded a 20% improvement in stone-passage rates with alpha blockers, and the 95% CI of 1% to 37% just reached statistical significance. Shock-wave Lithotripsy and Ureteroscopy The majority of data collected were on SWL and URS and thus, the major analyses focused on these treatments. Because both SWL and URS are conducted using various techniques, the Panel categorized the data accordingly. For SWL, the Panel used the categories SWL in situ, SWL-bypass therapy, SWL-pushback, and SWL-other. For URS, the Panel initially used the categories URS-rigid, URS-semi-rigid, URS-flexible, URS-combined (groups where some patients received flexible and some rigid), and URSother. As the analysis proceeded, the categories for URS changed. In particular, rigid and semi-rigid procedures were combined into a single category, labeled URS-rigid, because the Panel believed these devices were sufficiently similar. Data for those few groups of patients who all were treated with flexible URS were captured in a category called URSflexible. Since many studies reported groups where flexible URS and rigid URS were both used and since the Panel concluded that rigid URS is often used when flexible URS is not, the Panel determined that broader analysis for flexible URS was appropriate. A category called URS-mixed-flexible included all groups that had some patients receiving flexible URS or unspecified URS. The URS-flexible groups are included in the URS- Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 5 mixed-flexible analysis. In addition to these subgroup analyses, overall analyses of all SWL groups and of all URS groups were performed. Data were analyzed for both efficacy and complications. Two efficacy outcomes were analyzed: stone-free rate and procedure counts. Complications were grouped into classes. For the complete groupings and complication results, see Appendix 10. Analyses were performed for the following patient groups where data were available. 1. Proximal stones ≤10 mm 2. Proximal stones >10 mm 3. Proximal stones regardless of size 4. Mid-ureteral stones ≤10 mm 5. Mid-ureteral stones >10 mm 6. Mid-ureteral stones regardless of size 7. Distal stones ≤10 mm 8. Distal stones >10 mm 9. Distal stones regardless of size Analyses of pediatric groups were attempted for the same nine groups, although data were lacking for many groups. Efficacy Outcomes Stone-free rates Stone-free rates were determined initially in several ways. The Panel defined stone free as completely stone free without residual fragments. If the author used the term “stone free” and did not indicate that it could include residual fragments, the panel Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 6 assumed that patients were completely stone free. Stone-free data were extracted at three time points: 1. After the first procedure 2. After all primary procedures (procedures of the same type, i.e., either all SWL or all URS) 3. After all procedures The initial analysis was performed separately for each time point. However, because most studies did not give data for all time points, the panel decided to use one time point from each study. If the study gave the stone-free rate after all primary procedures, that number was used. If not, and the study gave the stone-free rate after the first procedure, then that number was used. The stone-free rate after all procedures was never used. The intention of the Panel was to provide an estimate of the number of primary procedures and the stone-free rate after those procedures. Because many studies only provided stone-free rates after the first procedure, the estimates of stone-free rates may be a little low. However, since most patients are stone free after the first procedure, this error should be rather small. The results of the analysis of stone-free data are presented for the overall group in Table 1. The Table shows the number of patient groups (G) and total number of patients (P) that contributed to the analysis. A patient group frequently represents patients from a single study. However, a study may have contributed multiple groups if the patients were different in some way and the results were stratified in the article, e.g., if the article compared two types of rigid scopes, it might provide data for patients treated with each scope type. This would yield two groups in the group count even though it represented Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 7 only one study. It should be noted that there are relatively small numbers of patients and groups for which mid ureter stone data are available. There are also small numbers of patients for the categories SWL-bypass, SWL-pushback, and URS-flexible. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 8 Table 1. Stone-Free Rates for Shock-wave Lithotripsy and Ureteroscopy in the Overall Population Proximal Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary/First Treatments Overall G/P Median CI (2.5 - 97.5)% 41/642 (79 - 85)% 82% 28/476 1/59 12/160 83% 83% 80% (79 - 87)% (72 - 91)% (72 - 86)% G/P 14/886 1/67 5/578 1/59 7/182 46/224 4/40 18/691 28/155 81% 89% 87% 77% (77 - 85)% (75 - 97)% (82 - 91)% (71 - 83)% 9/243 1/1 5/134 4/109 Size <10mm Median CI (2.5 - 97.5)% (85 - 93)% 90% (84 - 97)% 92% (89 - 98)% 94% (72 - 91)% 83% (67 - 91)% 80% G/P 11/293 1/23 4/186 Size >10mm Media CI (2.5 - 97.5)% (55 - 79)% 68% (59 - 91)% 78% (59 - 92)% 78% 6/84 53% (39 - 67)% 8/230 79% (71 - 87)% 3/58 5/172 81% 81% (63 - 93)% (71 - 88)% Ureteroscopy All forms Flexible Mixed flexible Rigid Mid Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other (73 - 85)% (15 - 100)% (74 - 89)% (66 - 85)% 80% 84% 83% 77% Primary/First Treatments Overall Size <10mm Size >10mm G/P 31/160 1/14 19/115 Median 73% 71% 77% CI (2.5 - 97.5)% (66 - 79)% (45 - 89)% (69 - 84)% G/P 5/44 Median 84% CI (2.5 - 97.5)% (65 - 95)% G/P 2/15 Median 76% CI (2.5 97.5)% (36 - 97)% 2/14 91% (67 - 99)% 1/6 96% (67 - 100)% 11/442 65% (51 - 77)% 3/30 77% (47 - 95)% 1/9 66% (35 - 90)% 30/102 2/14 11/262 19/762 86% 88% 88% 85% (81 - 89)% (53 - 99)% (79 - 94)% (79 - 89)% 5/80 91% (81 - 96)% 5/73 78% (61 - 90)% 1/9 4/71 87% 92% (59 - 99)% (82 - 97)% 1/5 4/68 60% 80% (21 - 91)% (66 - 90)% Ureteroscopy All forms Flexible Mixed flexible Rigid Distal Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary/First Treatments Overall G/P Median CI (2.5 - 97.5)% 50/698 (73 - 75)%* 74% G/P 17/168 42/649 75% (73 - 75)%* 14/164 86% (79 - 92)% 9/965 74% (56 - 88)% 8/486 71% (57 - 82)% 3/35 90% (75 - 98)% 1/1 84% (15 - 100)% 59/595 1/2 9/431 50/552 94% 10% 93% 94% (93 - 95)% (0 - 67)% (89 - 96)% (93 - 96)% 13/162 97% (96 - 98)% 8/412 93% (88 - 96)% 1/38 12/158 97% 98% (88 - 100)% (96 - 99)% 1/10 7/402 79% 94% (50 - 96)% (90 - 97)% Size <10mm Median CI (2.5 - 97.5)% (80 - 91)% 86% G/P 10/966 Size >10mm CI (2.5 Median (57 - 87)% 74% Ureteroscopy All forms Flexible Mixed flexible Rigid Total Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary/First Treatments Size <10mm Size >10mm G/P 37/562 1/67 24/380 1/59 11/196 Median 86% 92% 85% 83% 88% CI (2.5 - 97.5)% (82 - 89)% (84 - 97)% (79 - 90)% (72 - 91)% (81 - 93)% G/P 27/2348 1/23 16/1627 Median 67% 78% 65% CI (2.5 97.5)% (59 - 75)% (59 - 91)% (53 - 76)% 10/698 70% (57 - 82)% 25/259 1/1 7/206 18/239 93% 84% 87% 95% (90 - 95)% (15 - 100)% (81 - 92)% (92 - 97)% 19/928 87% (83 - 90)% 5/94 14/834 81% 88% (67 - 92)% (85 - 91)% Ureteroscopy All forms Flexible Mixed flexible Rigid Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 9 Results are presented as medians of the posterior distribution (best central estimate) with 95% Bayesian CIs (credible intervals [confidence intervals]). Note that the results of the analysis of URS-all forms are uniformly better than those for SWL-all forms when all ureteral locations are combined and segregated by size. The Panel wondered if it could be shown that these results reached statistical significance for any of the respective ureteral locations. Unfortunately, RCTs comparing these treatments were generally lacking, making an accurate assessment impossible. However, the posterior distributions resulting from the meta-analysis can be subtracted, yielding a posterior for the difference between the treatments. If the CI of this result does not include 0, then the results may be considered to be statistically significantly different. This operation is mathematically justifiable but operationally risky: if patients receiving different treatments are different or if outcome measures are different, results may be meaningless. Nonetheless, the panel performed the comparison and found that URS stone-free rates were significantly better than SWL rates for distal ureteral stones ≤10 mm and >10 mm and for proximal ureteral stones >10 mm. The stone-free result of URS tended to be better than that of SWL for all mid-ureteral stones, but the difference was not statistically significant (likely related to small sample size). However, this did not reach statistical significance which may be related to the small number of patients in these respective groups. The results with URS using a flexible ureteroscope for proximal ureteral stones appear better than those achieved with a rigid device, but not at a statistically significant level. Stone-free results for pediatric patients are shown in Table 2. The very small numbers of patients in most groups, particularly for URS, makes comparisons among Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 10 treatments difficult. However, it does appear that SWL may be more effective in the pediatric subset than in the overall population, particularly in the mid and distal ureter. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 11 Table 2. Stone-Free Rates for Shock-wave Lithotripsy and Ureteroscopy, Pediatric Population Proximal Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary/First Treatments Overall G/P Median CI (2.5 - 97.5)% 7/1 81% (69 - 90)% 5/43 89% (72 - 98)% G/P 3/1 4/6 85% (65 - 96)% 1/19 99% (88 - 100)% 3/3 78% (56 - 93)% 4/24 85% (59 - 97)% 5/1 57% (25 - 85)% 1/3 4/1 6% 67% (0 - 54)% (38 - 90)% G/P Size <10mm Median CI (2.5 - 97.5)% Size >10mm Median CI (2.5 - 97.5)% 63% (21 - 94)% 1/1 98% (81 - 100)% 2/4 36% (5 - 81)% Ureteroscopy All forms Flexible Mixed flexible Rigid Primary/First Treatments Overall Mid Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Size <10mm Size >10mm G/P 6/3 Median 82% CI (2.5 - 97.5)% (63 - 94)% G/P 4/16 Median 80% CI (2.5 - 97.5)% (41 - 98)% G/P 1/6 Median 96% CI (2.5 - 97.5)% (67 - 100)% 4/3 88% (70 - 97)% 2/14 91% (67 - 99)% 1/6 96% (67 - 100)% 2/3 56% (8 - 96)% 2/2 50% (6 - 94)% 3/1 80% (52 0 96)% 1/5 78% (37 - 99)% 3/1 80% (52 - 96)% 1/5 78% (37 - 99)% Ureteroscopy All forms Flexible Mixed flexible Rigid Distal Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary/First Treatments Overall G/P Median CI (2.5 - 97.5)% 8/2 80% (68 - 90)% G/P 5/13 6/2 77% (63 - 87)% 3/11 84% (68 - 94)% 1/2 87% (71 - 97)% 2/2 95% (79 - 100)% 2/16 93% (72 - 100)% 1/1 84% (15 - 100)% 9/1 92% (86 - 96)% 2/29 89% (72 - 98)% 1/7 8/1 84% 93% (50 - 98)% (87- 96)% 2/29 89% (72 - 98)% Size <10mm Median CI (2.5 - 97.5)% 86% (78 - 92)% G/P 2/2 Size >10mm Median CI (2.5 - 97.5)% 83% (58 - 97)% Ureteroscopy All forms Flexible Mixed flexible Rigid Total Ureter Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary/First Treatments Size <10mm G/P Median CI (2.5 - 97.5)% 7/19 87% (80 - 93)% G/P 4/6 3/15 86% (70 - 96)% 1/4 93% (83 - 98)% 4/47 88% (72 - 97)% 3/1 55% (26 - 81)% 3/72 91% (81 - 97)% 1/5 78% (37 - 98)% 3/72 91% (81 - 97)% 1/5 78% (37 - 98)% Size >10mm Median CI (2.5 - 97.5)% 73% (52 - 89)% Ureteroscopy All forms Flexible Mixed flexible Rigid Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 12 Procedure counts Procedure counts were captured as three types: 1. Primary procedures – the number of times the first removal procedure was performed. 2. Secondary procedures – the number of times an alternative stone removal procedure(s) was performed. 3. Adjunctive procedures – additional procedures performed at a time other than when the primary or secondary procedures were performed; these could include procedures related to the primary/secondary procedures such as stent removals as well as procedures performed to deal with complications; most adjunctive procedures in the data presented represent stent removals. It is likely that many stent-related adjunctive procedures were underreported, and thus the adjunctive procedure count may be underestimated.. While it would have been desirable to calculate a total procedure count, few studies reported all three types of procedures. Thus, the three types were computed separately. While adding them together to obtain a total procedure count is possible, the fact that the data came from different studies reduces the meaning of such a sum. As mentioned in Chapter 2, it was not possible to perform a meta-analysis due to the lack of variance data, and only weighted averages could be computed. It was not possible to determine whether the procedure count results differed by statistically significant amounts due to a lack of variance data. The procedure count results for the overall population are shown in Tables 3A-D. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 13 Table 3A. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Overall Population, Proximal Ureteral Stones Stones – All Sizes Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary Treatment Weighted G/P Mean 1.31 37/5902 1.55 1/180 1.28 24/4567 1.10 1/59 11/1096 1.43 G/P Ureteroscopy All forms Flexible Mixed flexible Rigid Stones ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other 42/1634 5/124 16/447 26/1187 Primary Treatment Weighted G/P Mean 1.26 16/1243 1.36 1/67 1.28 8/1032 1.10 1/59 6/85 1.04 G/P Ureteroscopy All forms Flexible Mixed flexible Rigid Stones ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Weighted Mean 1.02 1.00 1.03 1.02 All forms Flexible Mixed flexible Rigid Adjunctive Treatment Weighted G/P Mean 0.24 13/1329 1.00 1/180 0.28 6/183 8/416 0.12 12/1715 0.06 6/966 0.09 G/P G/P 27/1831 Weighted Mean 0.26 6/197 21/1634 0.04 0.29 Weighted Mean 0.17 1.00 0.25 0.13 Secondary Treatment Weighted G/P Mean 5/150 0.14 14/1159 4/104 7/451 7/708 Adjunctive Treatment Weighted G/P Mean 0.77 3/114 1.00 1/67 0.45 2/47 3/112 0.15 2/38 0.11 G/P 5/119 Weighted Mean 0.64 2/18 3/101 0.28 0.70 9/277 Weighted Mean 1.02 9/701 Weighted Mean 0.08 3/36 6/241 1.00 1.02 9/701 0.08 Primary Treatment Weighted G/P Mean 1.49 11/510 2.00 1/23 1.52 4/424 Ureteroscopy Secondary Treatment Weighted G/P Mean 20/2131 0.07 Secondary Treatment Weighted G/P Mean 5/83 0.21 1/41 0.20 G/P Adjunctive Treatment Weighted G/P Mean 0.56 4/45 1.00 1/23 6/63 1.14 4/42 0.21 3/22 0.09 G/P G/P Weighted Mean 6/222 Weighted Mean 0.12 G/P 5/137 Weighted Mean 1.07 2/30 3/107 1.00 1.09 1/14 5/208 0.07 0.12 G/P, number of groups/number of patients. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 14 Table 3B. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Overall Population, Mid Ureteral Stones Mid Ureter – All Sizes Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary Treatment Weighted G/P Mean 10/291 1.11 1/14 1.07 1/13 1.20 Ureteroscopy All forms Flexible Mixed flexible Rigid Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Mid Ureter ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid 3/71 0.06 Adjunctive Treatment Weighted G/P Mean 4/241 0.23 1/14 0.14 3/38 0.13 8/264 1.11 6/245 0.21 3/189 0.26 G/P Weighted Mean 1.04 1.02 1.11 1.01 G/P G/P 15/934 Weighted Mean 0.07 2/66 13/868 0.21 0.06 Weighted Mean 0.09 1.00 0.26 0.05 25/686 2/53 10/180 15/506 Mid Ureter ≤10 mm Secondary Treatment Weighted G/P Mean 9/316 0.18 Primary Treatment Weighted G/P Mean 8/444 1.20 5/416 1.21 3/28 1.00 G/P 7/241 Weighted Mean 1.02 1/9 6/232 1.00 1.02 Primary Treatment Weighted G/P Mean 4/148 1.52 3/129 1.55 1/19 1.32 G/P 3/18 Weighted Mean 1.00 1/5 2/13 1.00 1.00 Secondary Treatment Weighted G/P Mean 2/80 0.15 8/357 1/40 3/66 5/291 Adjunctive Treatment Weighted G/P Mean 2/80 0.15 G/P 7/671 Weighted Mean 0.06 3/99 Weighted Mean 0.71 7/671 0.06 3/99 0.71 Secondary Treatment Weighted G/P Mean G/P G/P Adjunctive Treatment Weighted G/P Mean G/P 3/119 Weighted Mean 0.18 1/5 Weighted Mean 0.20 3/119 0.18 1/5 0.20 G/P, number of groups/number of patients. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 15 Table 3C. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Overall Population, Distal Ureteral Stones Distal Ureter – All Sizes Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary Treatment Weighted G/P Mean 48/7117 1.22 Secondary Treatment Weighted G/P Mean 30/5069 0.12 Adjunctive Treatment Weighted G/P Mean 15/3875 0.03 38/5963 1.26 23/4297 0.12 13/3500 0.03 10/1154 1.03 7/772 0.13 2/375 0.02 G/P Weighted Mean 1.04 1.00 1.01 1.04 G/P G/P 25/5124 Weighted Mean 0.03 24/2848 Weighted Mean 0.36 25/5124 0.03 24/2848 0.36 Ureteroscopy All forms Flexible Mixed flexible Rigid Distal Ureter ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other 56/5308 1/2 7/277 49/5031 Primary Treatment Weighted G/P Mean 19/2031 1.31 14/1659 1.20 5/372 1.80 G/P 15/1326 Weighted Mean 1.01 1/38 14/1288 1.00 1.01 Ureteroscopy All forms Flexible Mixed flexible Rigid Distal Ureter ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Secondary Treatment Weighted G/P Mean 7/250 0.13 Adjunctive Treatment Weighted G/P Mean 7/250 0.13 G/P 11/1131 Weighted Mean 0.05 6/397 Weighted Mean 0.83 11/1131 0.05 6/397 0.83 G/P Primary Treatment Weighted G/P Mean 13/1065 1.43 Secondary Treatment Weighted G/P Mean 3/1026 0.10 11/1045 1.43 3/1026 0.10 2/20 1.30 G/P G/P 5/231 Weighted Mean 1.02 2/148 Weighted Mean 0.14 1/110 Weighted Mean 1.00 1/10 4/221 1.00 1.02 2/148 0.14 1/110 1.00 Ureteroscopy All forms Flexible Mixed flexible Rigid Adjunctive Treatment Weighted G/P Mean G/P G/P, number of groups/number of patients. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 16 Table 3D. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Overall Population, Total Ureteral Stones Total Ureter ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Primary Treatment Weighted G/P Mean 29/4577 1.33 1/67 1.36 20/3872 1.24 1/59 1.10 7/579 1.95 G/P Ureteroscopy All forms Flexible Mixed flexible Rigid Total Ureter ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other 17/1474 1/1 3/83 14/1391 Primary Treatment Weighted G/P Mean 21/1860 1.49 1/23 2.00 14/1771 1.50 Adjunctive Treatment Weighted G/P Mean 6/152 0.61 1/67 1.00 2/47 0.45 8/282 0.13 3/38 0.11 3/38 0.11 G/P G/P 8/711 Weighted Mean 0.05 8/711 0.05 Weighted Mean 0.78 1.00 0.28 0.81 Secondary Treatment Weighted G/P Mean 9/1113 0.11 4/1067 0.10 7/381 1/1 2/18 5/363 Adjunctive Treatment Weighted G/P Mean 3/45 0.56 1/23 1.00 6/66 1.18 5/46 0.28 2/22 0.09 G/P G/P 6/234 Weighted Mean 0.08 G/P 13/494 Weighted Mean 1.04 3/129 Weighted Mean 0.89 4/66 9/428 1.02 1.04 1/14 5/220 0.07 0.08 1/14 2/115 0.21 0.97 Ureteroscopy All forms Flexible Mixed flexible Rigid Weighted Mean 1.02 1.00 1.00 1.02 Secondary Treatment Weighted G/P Mean 11/320 0.13 G/P, number of groups/number of patients. Procedure count results for pediatric patients are shown in Tables 4A-D. Again, the numbers of patients with available data were small and did not support meaningful comparisons among treatments. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 17 Table 4A. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Pediatric Population, Proximal Ureteral Stones Proximal Ureter – All Sizes Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Proximal Ureter ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Proximal Ureter≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy Primary Treatment Weighted G/P Mean 5/83 1.28 3/49 1.39 Secondary Treatment Weighted G/P Mean 3/38 0.05 1/13 0.08 Adjunctive Treatment Weighted G/P Mean 1/5 0.00 2/34 1.12 2/25 0.04 1/5 0.00 G/P G/P 7/38 Weighted Mean 0.34 G/P 6/27 Weighted Mean 1.00 1/9 Weighted Mean 1.00 1/3 5/24 1.00 1.00 2/6 5/32 0.50 0.31 1/9 1.00 Primary Treatment Weighted G/P Mean 6/69 1.12 Secondary Treatment Weighted G/P Mean 1/3 0.00 Adjunctive Treatment Weighted G/P Mean 1/3 0.00 1/19 1.42 5/50 1.00 1/3 0.00 1/3 0.00 G/P G/P 5/156 Weighted Mean 0.12 G/P 2/55 Weighted Mean 1.07 3/101 Weighted Mean 0.70 2/55 1.07 5/156 0.12 3/101 0.70 Primary Treatment Weighted G/P Mean 4/16 1.38 Secondary Treatment Weighted G/P Mean 2/2 0.00 Adjunctive Treatment Weighted G/P Mean 2/2 0.00 1/12 1.50 3/4 1.00 2/2 0.00 2/2 0.00 G/P Weighted Mean G/P Weighted Mean G/P Weighted Mean All forms Flexible Mixed flexible Rigid G/P, number of groups/number of patients. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 18 Table 4B. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Pediatric Population, Mid Ureteral Stones Mid Ureter – All Sizes Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Mid Ureter ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Mid Ureter ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Primary Treatment Weighted G/P Mean 4/32 1.44 Secondary Treatment Weighted G/P Mean 1/9 0.11 3/29 1.48 1/9 1/3 G/P 4/18 1.00 Weighted Mean 1.00 4/18 1.00 G/P Primary Treatment Weighted G/P Mean 5/42 0.67 2/14 0.02 3/28 2/53 1.00 Weighted Mean 1.08 2/53 1.08 G/P Primary Treatment Weighted G/P Mean 1/6 1.33 1/6 0.11 2/12 Weighted Mean 0.17 2/12 Weighted Mean 0.75 2/12 0.17 2/12 0.75 Secondary Treatment Weighted G/P Mean G/P Adjunctive Treatment Weighted G/P Mean 4/145 Weighted Mean 0.09 3/99 Weighted Mean 0.71 4/145 0.09 3/99 0.71 G/P Secondary Treatment Weighted G/P Mean G/P Adjunctive Treatment Weighted G/P Mean 1.33 1/5 Weighted Mean 1.00 1/5 1.00 G/P Adjunctive Treatment Weighted G/P Mean 1/5 Weighted Mean 0.20 1/5 0.20 G/P 1/5 Weighted Mean 0.20 1/5 0.20 G/P G/P, number of groups/number of patients. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 19 Table 4C. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Pediatric Population, Distal Ureteral Stones Distal Ureter – All Sizes Primary Treatment Weighted G/P Mean 7/212 1.38 Shock-wave Lithotripsy All forms Bypass In situ Pushback Other 6/188 1.43 4/98 1/24 G/P 10/185 1.00 Weighted Mean 1.05 2/24 8/161 1.00 1.06 G/P Ureteroscopy All forms Flexible Mixed flexible Rigid Secondary Treatment Weighted G/P Mean 4/98 0.08 Distal Ureter ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Distal Ureter ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy Primary Treatment Weighted G/P Mean 6/161 1.35 7/190 5/96 1/17 6/173 0.06 0.09 1/17 4/79 0.12 0.85 Secondary Treatment Weighted G/P Mean 1/14 0.36 1/14 3/42 G/P 4/109 1.00 Weighted Mean 1.03 1/17 3/92 1.00 1.04 3/25 1.44 1/1 1.00 Weighted Mean G/P 0.07 Weighted Mean 0.72 1.48 Primary Treatment Weighted G/P Mean 4/26 1.42 2/43 Weighted Mean 0.09 3/119 G/P 0.08 Adjunctive Treatment Weighted G/P Mean 2/43 0.07 G/P Adjunctive Treatment Weighted G/P Mean 0.36 8/269 Weighted Mean 0.10 4/143 Weighted Mean 0.71 1/17 7/252 0.06 0.10 1/17 3/126 0.12 0.79 Secondary Treatment Weighted G/P Mean G/P Weighted Mean G/P Adjunctive Treatment Weighted G/P Mean G/P Weighted Mean All forms Flexible Mixed flexible Rigid G/P, number of groups/number of patients. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 20 Table 4D. Procedure Counts for Shock-wave Lithotripsy and Ureteroscopy in the Pediatric Population, Total Ureteral Stones Total Ureter ≤10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Total Ureter ≥10 mm Shock-wave Lithotripsy All forms Bypass In situ Pushback Other Ureteroscopy All forms Flexible Mixed flexible Rigid Primary Treatment Weighted G/P Mean 7/196 1.37 Secondary Treatment Weighted G/P Mean 3/17 0.30 Adjunctive Treatment Weighted G/P Mean 2/3 0.00 3/152 1.48 1/14 0.36 4/44 2/3 3/75 1.00 Weighted Mean 1.05 5/167 0.00 Weighted Mean 0.09 3/109 0% Weighted Mean 0.58 1/17 2/58 1.00 1.07 1/17 4/150 0.06 0.09 1/17 2/92 0.12 0.67 G/P Primary Treatment Weighted G/P Mean 3/48 1.39 G/P Secondary Treatment Weighted G/P Mean 1/2 0.00 1//43 1.44 2/5 G/P 1/5 1.00 Weighted Mean 1.00 1/5 1.00 G/P 1/2 2/3 G/P Adjunctive Treatment Weighted G/P Mean 1/2 0.00 1/2 G/P 1/5 0.00 Weighted Mean 0.20 1/5 0% Weighted Mean 0.20 1/5 0.20 1/5 0.20 G/P, number of groups/number of patients. Complications and Side Effects The important complications and side effects are reported grouped into the following categories: 1. Cardiovascular 2. Death 3. Sepsis 4. Steinstrasse 5. Stricture 6. Transfusion Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 21 7. Ureteral injury 8. Ureteral obstruction 9. Urinary tract infections (UTI) 10. Overall significant The last category included data from articles that did not specify the nature of the complications but simply provided a count of significant complications. This most frequently occurred when the study indicated that there were no significant complications. The numbers of specific complications listed in an article were not summed and counted as overall significant complications. Thus, the estimates for this category are probably substantially underestimated and are included to show that there were studies that specified that no complications occurred. The Panel made no inferences about the nonoccurrence of complications. If an article did not mention a complication, even if other complications were listed, no assumption was made that the complication did not occur. This decision may have caused the presented data to be overestimated because studies where the complication occurred and was reported were more likely to be included. However, since many studies did not report complications or may have omitted complications, the complication rates may be underestimated. It is not known to what extent these competing sources of inaccuracy counteract each other. For very rare events, such as death, for which the few recorded instances are probably reported, the estimates given are significant overestimates. The complication rate for the overall population by treatment, size, and location are shown in Table 5. The Panel opted not to compare treatments with regard to statistically significant differences since articles varied in the complications reported and Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 22 computing a statistical measure of difference was likely to be misleading. Estimates for rare events, such as death, are included to indicate that they can occur, but the estimates are unrealistically high. This situation is likely also true for other serious but rare complications. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 23 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Cardiovascular Distal Ureter Death No. of Groups No. of Pts Med. Prob. 95% CI SWL - all types SWL - in situ URS - all types URS - rigid 1 1 1 1 395 395 32 32 2% 2% 4% 4% (1 - 3)% (1 - 3)% (0 - 14)% (0 - 14)% Proximal Ureter SWL - all types SWL - other URS - all types URS - mixed flexible 1 1 1 1 111 111 109 109 0% 0% 2% 2% (0 - 2)% (0 - 2)% (0 - 6)% (0 - 6)% Distal Ureter SWL - all types SWL - in situ 2 2 1,185 1,185 0% 0% (0 - 1)% (0 - 0)% Size Treatment Distal Ureter ≤10 mm SWL - all types SWL - in situ 1 1 341 341 0% 0% (0 - 1)% (0 - 1)% Distal Ureter ≥10 mm SWL - all types SWL - in situ 1 1 105 105 0% 0% (0 - 2)% (0 - 2)% SWL - all types SWL - in situ URS - all types URS - flexible URS - mixed flexible 2 2 1 1 1 238 238 40 40 40 0% 0% 1% 1% 1% (0 - 1)% (0 - 1)% (0 - 6)% (0 - 6)% (0 - 6)% Mid Ureter Mid Ureter ≤10 mm SWL - all types SWL - in situ 1 1 44 44 1% 1% (0 - 6)% (0 - 6)% Mid Ureter ≥10 mm SWL - all types SWL - in situ 1 1 30 30 1% 1% (0 - 8)% (0 - 8)% Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 24 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Size Proximal Ureter Overall Significant No. of Groups No. of Pts Med. Prob. 95% CI SWL - all types SWL - in situ URS - all types URS - flexible URS - mixed flexible 2 2 1 1 1 1,143 1,143 84 84 84 0% 0% 0% 0% 0% (0 - 0)% (0 - 0)% (0 - 3)% (0 - 3)% (0 - 3)% Treatment Proximal Ureter ≤10 mm SWL - all types SWL - in situ 1 1 151 151 0% 0% (0 - 2)% (0 - 2)% Proximal Ureter ≥10 mm SWL - all types SWL - in situ 1 1 117 117 0% 0% (0 - 2)% (0 - 2)% SWL - all types SWL - in situ SWL - other URS - all types URS - mixed flexible URS - rigid 11 9 2 18 3 15 2,027 1,974 53 1,902 132 1,770 1% 3% 7% 9% 7% (0 - 2)% (0 - 1)% (0 - 11)% (5 - 10)% (4 - 16)% (4 - 10)% 1% Distal Ureter Distal Ureter ≤10 mm SWL - all types SWL - in situ SWL - other URS - all types URS - rigid 4 3 1 6 6 809 800 9 532 532 1% 0% 2% 6% 6% (0 - 2)% (0 - 1)% (0 - 24)% (3 - 12)% (3 - 12)% Distal Ureter ≥10 mm SWL - all types SWL - in situ URS - all types URS - rigid 2 2 3 3 197 197 177 177 1% 1% 16% 16% (0 - 3)% (0 - 3)% (5 - 35)% (5 - 35)% Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 25 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Overall Significant Stone Location Mid Ureter Size Treatment SWL - all types SWL - in situ SWL - other URS - all types URS - flexible URS - mixed flexible URS - rigid Mid Ureter ≤10 mm Mid Ureter ≥10 mm Proximal Ureter Proximal Ureter ≤10 mm Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology No. of Groups 4 2 2 9 1 3 6 No. of Pts 149 125 24 126 1 27 99 Med. Prob. 3% 1% 8% 14% 16% 13% 15% 95% CI (0 - 9)% (0 - 6)% (0 - 34)% (8 - 22)% (0 - 85)% (2 - 34)% (8 - 24)% SWL - all types SWL - in situ SWL - other URS - all types URS - rigid 2 1 1 1 1 91 90 1 15 15 1% 0% 16% 14% 14% (0 - 7)% (0 - 3)% (0 - 85)% (3 - 36)% (3 - 36)% URS - all types URS - rigid 1 1 8 8 14% 14% (1 - 45)% (1 - 45)% SWL - all types SWL - in situ SWL - other URS - all types URS - flexible URS - mixed flexible URS - rigid 6 3 3 13 1 5 8 622 453 169 383 8 190 193 4% 1% 11% 11% 3% 12% 10% (1 - 12)% (0 - 5)% (2 - 34)% (6 - 17)% (0 - 26)% (4 - 26)% (6 - 17)% SWL - all types SWL - in situ SWL - other URS - all types URS - mixed flexible URS - rigid 2 1 1 3 2 1 165 151 14 120 98 22 1% 0% 2% 12% 15% 1% (0 - 7)% (0 - 2)% (0 - 16)% (2 - 32)% (1 - 47)% (0 - 11)% 26 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Sepsis Stone Location Size Treatment Proximal Ureter ≥10 mm Distal Ureter No. of Groups No. of Pts Med. Prob. 95% CI SWL - all types SWL - in situ URS - all types URS - mixed flexible URS - rigid 1 1 4 2 2 117 117 108 42 66 0% 0% 17% 24% 10% (0 - 2)% (0 - 2)% (6 - 34)% (2 - 69)% (3 - 21)% SWL - all types SWL - in situ SWL - other URS - all types URS - mixed flexible URS - rigid 6 5 1 7 1 6 2,019 2,003 16 1,954 109 1,845 3% 3% 1% 2% 0% 2% (2 - 5)% (2 - 5)% (0 - 14)% (1 - 4)% (0 - 2)% (1 - 4)% Distal Ureter ≤10 mm SWL - all types SWL - in situ SWL - other URS - all types URS - rigid 2 1 1 1 1 53 44 9 12 12 4% 3% 2% 2% 2% (1 - 14)% (0 - 10)% (0 - 24)% (0 - 19)% (0 - 19)% Distal Ureter ≥10 mm SWL - all types SWL - in situ 1 1 342 342 4% 4% (2 - 6)% (2 - 6)% SWL - all types SWL - in situ SWL - other URS - all types URS - flexible URS - mixed flexible 2 1 1 4 1 2 398 396 2 199 40 43 5% 2% 10% 4% 1% 5% (0 - 20)% (1 - 4)% (0 - 67)% (1 - 11)% (0 - 6)% (0 - 24)% Mid Ureter Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 27 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Sepsis Steinstrasse Stone Location Size Treatment URS - rigid Mid Ureter ≤10 mm Proximal Ureter No. of Groups 2 No. of Pts 156 Med. Prob. 3% 95% CI (0 - 14)% SWL - all types SWL - other 1 1 1 1 16% 16% (0 - 85)% (0 - 85)% SWL - all types SWL - in situ SWL - other URS - all types URS - flexible URS - mixed flexible URS - rigid 5 2 3 8 1 4 4 704 499 205 360 84 213 147 3% 3% 2% 4% 0% 3% 5% (2 - 4)% (2 - 5)% (1 - 6)% (2 - 6)% (0 - 3)% (1 - 7)% (2 - 10)% Proximal Ureter ≤10 mm SWL - all types SWL - other SWL - all types SWL - in situ 1 1 1 1 14 14 41 41 2% 2% 1% 1% (0 - 16)% (0 - 16)% (0 - 6)% (0 - 6)% Proximal Ureter ≥10 mm URS - all types URS - rigid 1 1 41 41 1% 1% (0 - 6)% (0 - 6)% Distal Ureter SWL - all types SWL - other 1 1 26 26 4% 4% (0 - 17)% (0 - 17)% Mid Ureter SWL - all types SWL - other 1 1 37 37 8% 8% (2 - 20)% (2 - 20)% Proximal Ureter SWL - all types SWL - in situ 3 1 235 50 5% 6% (2 - 10)% (2 - 15)% Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 28 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Stricture Distal Ureter Size Treatment SWL - other URS - all types URS - mixed flexible No. of Groups 2 1 1 No. of Pts 185 109 109 Med. Prob. 4% 0% 0% 95% CI (1 - 10)% (0 - 2)% (0 - 2)% SWL - all types SWL - in situ URS - all types URS - mixed flexible URS - rigid 2 2 16 2 14 609 609 1,911 76 1,835 0% 0% 1% 4% 1% (0 - 1)% (0 - 1)% (1 - 2)% (1 - 14)% (1 - 2)% Distal Ureter ≤10 mm SWL - all types SWL - in situ URS - all types URS - rigid 1 1 2 2 28 28 125 125 1% 1% 2% 2% (0 - 9)% (0 - 9)% (0 - 9)% (0 - 9)% Distal Ureter ≥10 mm SWL - all types SWL - in situ 1 1 63 63 0% 0% (0 - 4)% (0 - 4)% SWL - all types SWL - in situ URS - all types URS - flexible URS - mixed flexible URS - rigid 1 1 7 1 4 3 43 43 326 1 43 283 1% 1% 4% 16% 8% 2% (0 - 6)% (0 - 6)% (2 - 7)% (0 - 85)% (2 - 22)% (1 - 6)% Mid Ureter Mid Ureter ≤10 mm SWL - all types SWL - in situ 1 1 15 15 1% 1% (0 - 15)% (0 - 15)% Mid Ureter ≥10 mm SWL - all types 1 24 1% (0 - 10)% Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 29 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Size Proximal Ureter Transfusion No. of Groups 1 No. of Pts 24 Med. Prob. 1% 95% CI (0 - 10)% SWL - all types SWL - in situ SWL - other URS - all types URS - flexible URS - mixed flexible URS - rigid 2 1 1 8 1 4 4 124 13 111 987 8 164 823 2% 2% 0% 2% 3% 3% 2% (0 - 8)% (0 - 17)% (0 - 2)% (1 - 5)% (0 - 26)% (1 - 8)% (0 - 5)% Treatment SWL - in situ Proximal Ureter ≤10 mm URS - all types URS - rigid 1 1 64 64 0% 0% (0 - 4)% (0 - 4)% Proximal Ureter ≥10 mm URS - all types URS - rigid 1 1 51 51 0% 0% (0 - 5)% (0 - 5)% SWL - all types SWL - in situ URS - all types URS - mixed flexible 1 1 1 1 91 91 109 109 0% 0% 0% 0% (0 - 3)% (0 - 3)% (0 - 2)% (0 - 2)% Distal Ureter Distal Ureter ≤10 mm SWL - all types SWL - in situ 1 1 28 28 1% 1% (0 - 9)% (0 - 9)% Distal Ureter ≥10 mm SWL - all types SWL - in situ 1 1 63 63 0% 0% (0 - 4)% (0 - 4)% SWL - all types SWL - in situ 1 1 43 43 1% 1% (0 - 6)% (0 - 6)% Mid Ureter Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 30 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Ureteral Injury Stone Location Size Treatment No. of Groups No. of Pts Med. Prob. 95% CI Mid Ureter ≤10 mm SWL - all types SWL - in situ 1 1 15 15 1% 1% (0 - 15)% (0 - 15)% Mid Ureter ≥10 mm SWL - all types SWL - in situ 1 1 28 28 1% 1% (0 - 9)% (0 - 9)% Proximal Ureter URS - all types URS - mixed flexible 1 1 17 17 1% 1% (0 - 14)% (0 - 14)% Distal Ureter SWL - All types SWL - in situ URS - all types URS - mixed flexible URS - rigid 1 1 23 4 19 45 45 4,529 298 4,231 1% 1% 3% 5% 3% (0 - 5)% (0 - 5)% (3 - 4)% (3 - 8)% (2 - 4)% Distal Ureter ≤10 mm URS - all types URS - rigid 3 3 215 215 2% 2% (0 - 5)% (0 - 5)% Distal Ureter ≥10 mm URS - all types URS - rigid 1 1 71 71 0% 0% (0 - 3)% (0 - 3)% URS - all types URS - flexible URS - mixed flexible URS - rigid 10 1 4 6 514 40 91 423 6% 1% 5% 6% (3 - 8)% (0 - 6)% (1 - 13)% (3 - 9)% URS - all types URS - rigid 2 2 31 31 8% 8% (0 - 39)% (0 - 39)% Mid Ureter Mid Ureter ≤10 mm Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 31 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Size Treatment Mid Ureter ≥10 mm Proximal Ureter Ureteral Obstruction No. of Groups No. of Pts Med. Prob. 95% CI URS - all types URS - rigid 1 1 33 33 1% 1% (0 - 7)% (0 - 7)% SWL - all types SWL - in situ SWL - other URS - all types URS - flexible URS - mixed flexible URS - rigid 2 1 1 10 1 3 7 124 13 111 1,005 84 200 805 2% 2% 0% 6% 0% 2% 7% (0 - 8)% (0 - 17)% (0 - 2)% (3 - 9)% (0 - 3)% (0 - 6)% (4 - 12)% Proximal Ureter ≤10 mm URS - all types URS - rigid 3 3 74 74 9% 9% (1 - 28)% (1 - 28)% Proximal Ureter ≥10 mm URS - all types URS - rigid 2 2 92 92 1% 1% (0 - 6)% (0 - 6)% SWL - All types SWL - in situ SWL - other URS - all types URS - rigid 5 4 1 2 2 330 314 16 185 185 3% 2% 1% 2% 2% (1 - 6)% (1 - 6)% (0 - 14)% (1 - 6)% (1 - 6)% Distal Ureter Distal Ureter ≤10 mm SWL - all types SWL - in situ SWL - other 4 3 1 95 86 9 5% 4% 2% (1 - 11)% (1 - 12)% (0 - 24)% Distal Ureter ≥10 mm SWL - all types SWL - in situ 1 1 63 63 0% 0% (0 - 4)% (0 - 4)% Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 32 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Size Mid Ureter No. of Pts Med. Prob. 95% CI SWL - all types SWL - in situ SWL - other URS - all types URS - mixed flexible 3 2 1 1 1 64 62 2 25 25 9% 6% 10% 1% 1% (1 - 24)% (0 - 25)% (0 - 67)% (0 - 9)% (0 - 9)% Mid Ureter ≤10 mm SWL - all types SWL - in situ SWL - other 2 1 1 16 15 1 11% 1% 16% (0 - 46)% (0 - 15)% (0 - 85)% Mid Ureter ≥10 mm SWL - all types SWL - in situ 1 1 28 28 1% 1% (0 - 9)% (0 - 9)% SWL - all types SWL - bypass SWL - in situ SWL - other 4 1 2 1 430 90 320 20 2% 2% 2% 1% (1 - 4)% (0 - 7)% (0 - 6)% (0 - 12)% SWL - all types SWL - other 1 1 14 14 2% 2% (0 - 16)% (0 - 16)% SWL - all types SWL - in situ SWL - other URS - all types URS - rigid 3 1 2 3 3 87 45 42 458 458 4% 5% 3% 4% 4% (1 - 12)% (1 - 14)% (0 - 13)% (2 - 7)% (2 - 7)% SWL - all types SWL - other 1 1 9 9 2% 2% (0 - 24)% (0 - 24)% Proximal Ureter Proximal Ureter Urinary Tract Infection No. of Groups Treatment ≤10 mm Distal Ureter Distal Ureter ≤10 mm Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 33 Table 5. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) by Treatment, Size, and Location in the Overall Population Complication Category Stone Location Size Mid Ureter Mid Ureter ≤10 mm Proximal Ureter Proximal Ureter ≤10 mm Treatment URS - all types URS - rigid No. of Groups 1 1 No. of Pts 12 12 Med. Prob. 2% 2% 95% CI (0 - 19)% (0 - 19)% SWL - all types SWL - other URS - all types URS - rigid 1 1 1 1 37 37 63 63 6% 6% 2% 2% (1 - 16)% (1 - 16)% (0 - 7)% (0 - 7)% SWL - all types SWL - other 1 1 1 1 16% 16% (0 - 85)% (0 - 85)% SWL - all types SWL - bypass SWL - in situ SWL - other URS - all types URS - mixed flexible URS - rigid 5 1 1 3 2 1 1 360 90 65 205 224 109 115 4% 1% 8% 4% 4% 4% 3% (2 - 7)% (0 - 5)% (3 - 16)% (1 - 8)% (1 - 8)% (1 - 8)% (1 - 7)% SWL - all types SWL - other 1 1 14 14 2% 2% (0 - 16)% (0 - 16)% No., number; Prob., probability; SWL, shock-wave lithotripsy; URS, ureteroscopy Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 34 Table 6 summarizes complications for all pediatric groups. Since there are few groups and patients, it was not possible to stratify data by stone size or location. Table 6. Complication Occurrence Rates with Shock-Wave Lithotripsy (SWL) and Ureteroscopy (URS) in the Pediatric Population SWL Overall SWL in Situ SWL - Other G/P Median Bleeding Overall Significant Complications 2/206 5% CI (2.5 - 97.5)% (0 - 24)% 1/38 1% (0 - 6)% Pain 3/106 18% (9 - 30)% 3/106 18% Retention (0 - 7)% 1/63 2% (0 - 7)% Sepsis 1/63 2/101 2% 4% (1 - 12)% 1/63 5% (1 - 12)% G/P Median 2/206 5% CI (2.5 - 97.5)% (0 - 24)% G/P Median CI (2.5 - 97.5)% 1/38 1% (0 - 6)% 1/38 1% (0 - 6)% (9 - 30)% Skin 1/168 0% (0 - 1)% 1/168 0% (0 - 1)% Stricture 1/25 1% (0 - 9)% 1/25 1% (0 - 9)% Ureteral Obstruction 4/283 2/63 2% (1 - 6)% (1 - 6)% 1/38 1% (0 - 6)% (0 - 9)% 3/245 1/25 3% 2% 1% (0 - 9)% 1/38 1% (0 - 6)% Urinary Tract Infection URS Overall URS Mixed Flexible G/P Median Bleeding 1/66 17% CI (2.5 - 97.5)% (9 - 27)% Infection Overall Significant Complications 2/91 6% 5/65 Pain 3/98 1/26 Retention URS Rigid/Semi-rigid G/P Median CI (2.5 - 97.5)% 1/66 17% CI (2.5 - 97.5)% (9 - 27)% (2 - 13)% 1/25 5% (0 - 17)% 1/66 5% (1 - 12)% 5% (1 - 14)% 2/10 11% (1 - 41)% 3/55 4% (0 - 13)% 5% (1 - 13)% 3/98 5% (1 - 13)% 4% (0 - 17)% 1/26 4% (0 - 17)% 3/73 3% (0 - 9)% (2 - 11)% G/P Median Sepsis 3/73 3% (0 - 9)% Stent Migration 1/25 5% (0 - 17)% 1/25 5% (0 - 17)% Ureteral Injury 6/216 6% (3 - 10)% 1/29 4% (0 - 15)% 5/187 6% Ureteral Obstruction 1/26 1% (0 - 9)% 1/26 1% (0 - 9)% Urinary Tract Infection 1/12 2% (0 - 19)% 1/12 2% (0 - 19)% Stricture 5/106 5% (2 - 11)% 5/106 5% (2 - 11)% Other Long -term complications 1/43 12% (5 - 24)% 1/43 12% (5 - 24)% CI, confidence interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 35 Other Surgical Interventions Open surgery, laparoscopic stone removal, and percutaneous antegrade ureteroscopy were also considered by the Panel although relatively small numbers of studies reported on these procedures. Stone-free rate results are shown in Table 7, and procedure count data are shown in Tables 8A-D. Because these procedures are usually reserved for special cases, the reported data should not be used to compare procedures with each other or with SWL or URS. As expected, these more invasive procedures yielded high stone-free rates. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 36 Table 7. Stone-Free Rates for Other Surgical Interventions in the Overall Population Proximal Ureter Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Mid Ureter Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Distal Ureter Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Total Ureter Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Primary/First Treatments Overall G/P Median CI (2.5 - 9.5)% 5/91 84% (75 - 91)% 4/176 95% (90 - 98)% G/P 1/1 Size <10mm Median CI (2.5 - 9.5)% 84% (15 - 100)% G/P Median G/P Median G/P 2/7 Median 76% Primary/First Treatments Overall G/P 1/10 Median 98% CI (2.5 97.5)% (78 - 100)% Median 86% CI (2.5 - 9.5)% (64 - 97)% 1/122 97% (92 - 99)% Median CI (2.5 - 9.5)% CI (2.5 - 9.5)% G/P Median G/P Median G/P 5/37 2/89 Median 85% 97% Size >10mm Size <10mm Primary/First Treatments Overall G/P Size >10mm Median CI (2.5 - 9.5)% 81% (54 - 96)% 97% (92 - 100)% Size <10mm Primary/First Treatments Overall G/P 1/15 G/P 3/13 2/89 CI (2.5 - 9.5)% Size >10mm Size <10mm CI (2.5 - 9.5)% (38 - 96)% CI (2.5 - 9.5)% CI (2.5 - 9.5)% Size >10mm CI (2.5 - 9.5)% (68 - 95)% (92 - 100)% G/P, number of groups/number of patients; PNL, percutaneous antegrade ureteroscopy. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 37 Table 8A. Procedure Counts for Other Surgical Interventions in the Overall Population, Proximal Ureteral Stones Proximal Ureter – All Sizes Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Proximal Ureter ≤10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Proximal Ureter ≥10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Primary Treatment Weighted G/P Mean 5/38 1.00 4/176 1.05 Secondary Treatment Weighted G/P Mean 2/61 0.18 3/238 0.04 Adjunctive Treatment Weighted G/P Mean 1/2 1.00 5/242 0.73 Primary Treatment Weighted G/P Mean 2/7 1.00 Secondary Treatment Weighted G/P Mean 1/6 0.17 Adjunctive Treatment Weighted G/P Mean 2/7 1.00 Primary Treatment Weighted G/P Mean 4/19 1.00 2/89 1.00 Secondary Treatment Weighted G/P Mean 2/12 0.17 1/66 0.02 Adjunctive Treatment Weighted G/P Mean 2/7 1.00 3/155 0.58 G/P, number of groups/number of patients; PNL, percutaneous antegrade ureteroscopy. Table 8B. Procedure Counts for Other Surgical Interventions in the Overall Population, Mid Ureteral Stones Mid Ureter – All Sizes Other Surgeries Primary Treatment Weighted G/P Mean Secondary Treatment Weighted G/P Mean Adjunctive Treatment Weighted G/P Mean Primary Treatment Weighted G/P Mean 1/6 1.00 Secondary Treatment Weighted G/P Mean 1/6 0.17 Adjunctive Treatment Weighted G/P Mean 1/6 1.00 Primary Treatment Weighted G/P Mean 1/6 1.00 Secondary Treatment Weighted G/P Mean 1/6 0.17 Adjunctive Treatment Weighted G/P Mean 1/6 1.00 Laparoscopic Stone Removal PNL Open Surgery Mid Ureter ≤10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Mid Ureter ≥10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery G/P, number of groups/number of patients; PNL, percutaneous antegrade ureteroscopy. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 38 Table 8C. Procedure Counts for Other Surgical Interventions in the Overall Population, Distal Ureteral Stones Distal Ureter – All Sizes Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Distal Ureter ≤10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Distal Ureter ≥10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Primary Treatment Weighted G/P Mean 1/15 1.00 Secondary Treatment Weighted G/P Mean 1/15 0.13 Adjunctive Treatment Weighted G/P Mean Primary Treatment Weighted G/P Mean 1/6 1.00 Secondary Treatment Weighted G/P Mean 1/6 0.17 Adjunctive Treatment Weighted G/P Mean 1/6 1.00 Primary Treatment Weighted G/P Mean 1/6 1.00 Secondary Treatment Weighted G/P Mean 1/6 0.17 Adjunctive Treatment Weighted G/P Mean 1/61 1.00 1/122 1.00 G/P, number of groups/number of patients; PNL, percutaneous antegrade ureteroscopy. Table 8D. Procedure Counts for Other Surgical Interventions in the Overall Population, Total Ureteral Stones Total Ureter ≤10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Total Ureter ≥10 mm Other Surgeries Laparoscopic Stone Removal PNL Open Surgery Primary Treatment Weighted G/P Mean 2/7 1.00 Secondary Treatment Weighted G/P Mean 1/6 0.17 Adjunctive Treatment Weighted G/P Mean 2/7 1.00 Primary Treatment Secondary Treatment Adjunctive Treatment G/P 5/37 1/89 1/18 Weighted Mean 1.00 1.00 1.00 G/P 2/12 1/66 Weighted Mean 0.17 0.02 G/P 4/43 3/155 Weighted Mean 0.30 0.58 G/P, number of groups/number of patients; PNL, percutaneous antegrade ureteroscopy. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 39 A single pediatric report provided procedure counts for two patients who had one open procedure each. Two studies reported stone-free rates for children with open procedures (N=5 patients); the computed stone-free rate was 82% (95% CI: 43% to 99%). Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 40 Acknowledgements and Disclaimers The supporting systematic literature review and data analysis, and the drafting of this document were conducted by the EAU/AUA Nephrolithiasis Guideline Panel (hereinafter the Panel). Each association selected a Panel chair who in turn appointed the Panel members, urologists with specific expertise in this disease. The mission of the Panel was to develop either analysis- or consensus-based recommendations, depending on the type of evidence available and Panel processes to support optimal clinical practices in the management of ureteral calculi. This document was submitted to 81 urologists and other health care professionals for peer review. After revision of the document based upon the peer review comments, the guideline was submitted for approval to the Practice Guidelines Committee of the AUA and the Guidelines Office of the EAU. Then it was forwarded to the AUA Board of Directors and the EAU Board for final approval. Funding of the Panel and of the PGC was provided by the AUA and the EAU, although Panel members received no remuneration for their work. Each member of the PGC and of the Panel furnished a current conflict of interest disclosure to the AUA. The final report is intended to provide medical practitioners with a current understanding of the principles and strategies for the management of ureteral calculi. The report is based on an extensive review of available professional literature as well as clinical experience and expert opinion. Some of the medical therapies currently employed in the management of ureteral calculi have not been approved by the US Food and Drug Administration for this specific indication. Thus, doses and dosing regimens may deviate Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 53 from that employed for the Food and Drug Adminstration-approved indications, and this difference should be considered in the risk-versus-benefit assessment. This document provides guidance only, and does not establish a fixed set of rules or define the legal standard of care. As medical knowledge expands and technology advances, this guideline will change. Today it represents not absolute mandates but provisional proposals or recommendations for treatment under the specific conditions described. For all these reasons, the guideline does not preempt physician judgment in individual cases. Also, treating physicians must take into account variations in resources, and in patient tolerances, needs and preferences. Conformance with the guideline reflected in this document cannot guarantee a successful outcome. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology® 54 2007 Guideline for the Management of Ureteral Calculi Appendixes European Association of Urology American Urological Association Education and Research, Inc. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 1 Table of Contents Appendix 1: Ureteral Stones Guideline Update Panel Members and Consultants (1997) .............1 Appendix 2: EAU Working Group on Urolithiasis ........................................................................3 Appendix 3: Ureteral Stones Guideline Update Panel Members and Consultants (2007) ............4 Appendix 4: Article Status Report..................................................................................................6 Appendix 5: Article Extraction Form .............................................................................................8 Appendix 6: Bibliography of Extracted Articles Sorted by Primary Author................................13 Appendix 7: Bibliography of Extracted Articles Sorted by ProCite Number ..............................33 Appendix 8: Stone Free Rates for Observation Therapies by Size...............................................50 Appendix 9: Stone Free Rates for Medical Therapies by Size .....................................................51 Appendix 10: Complications Graphs............................................................................................52 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 2 Appendix 1: Ureteral Stones Guideline Update Panel Members and Consultants (1997) Members: Joseph W. Segura, M.D., F.A.C.S. (Chairman) The Carl Rosen Professor of Urology Department of Urology The Mayo Clinic Rochester, Minnesota Glenn M. Preminger, M.D., F.A.C.S. (Panel Facilitator) Professor, Department of Urology Duke University Medical Center Durham, North Carolina Dean G. Assimos, M.D., F.A.C.S. Associate Professor of Surgical Sciences Department of Urology The Bowman Gray School of Medicine Wake Forest University Winston-Salem, North Carolina Stephen P. Dretler, M.D., F.A.C.S. Clinical Professor of Surgery Harvard Medical School Director, Kidney Stone Center Massachusetts General Hospital Boston, Massachusetts Robert K. Kahn, M.D., F.A.C.S. Chief of Endourology California Pacific Medical Center San Francisco, California James E. Lingeman, M.D., F.A.C.S. Director of Research Methodist Hospital Institute for Kidney Stone Disease Associate Clinical Instructor in Urology Indiana University School of Medicine Indianapolis, Indiana Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 1 Joseph N. Macaluso, Jr., M.D., F.A.C.S. Managing Director The Urologic Institute of New Orleans Associate Professor of Clinical Urology Louisiana State University Medical Center School of Medicine New Orleans, Louisiana Consultants: Hanan S. Bell, Ph.D. (Consultant in Methodology) Seattle, Washington Patrick M. Florer (Database Design and Coordination) Dallas, Texas Curtis Colby (Editor) Washington, D.C. Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 2 Appendix 2: EAU Working Group on Urolithiasis Prof. Dr. H-G. Tiselius, Stockholm (S) (chairman) Prof. Dr. P. Alken, Mannheim (D) Mr. C. Buck, Glasgow (UK) Prof. Dr. P. Conort, Paris (F) Prof. Dr. M. Gallucci, Rome (I) Dr. Th. Knoll, Mannheim (D) Prof. Dr. Chr. Türk, Vienna (A) Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 3 Appendix 3: Ureteral Stones Guideline Update Panel Members and Consultants (2007) Members: Glenn M. Preminger, M.D., Co-Chair Division of Urologic Surgery Duke University Medical Center Durham, North Carolina Hans-Göran Tiselius, M.D., Ph.D.,Co-Chair Department of Urology, Karolinska University Hospital, Huddinge Division of Urology Karolinska Institutet Stockholm, Sweden Dean G. Assimos, M.D., Vice Chair Department of Urology Wake Forest University School of Medicine Winston-Salem, North Carolina Peter Alken, M.D., Ph.D. Department of Urology Klinikum Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg Mannheim, Germany Colin Buck, M.D., Ph.D. Brownlee House Carluke, Scotland United Kingdom Michele Gallucci, M.D., Ph.D. Urologia Istituto Regina Elena Rome, Italy Thomas Knoll, M.D., Ph.D. Department of Urology Klinikum Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg Mannheim, Germany Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 4 James E. Lingeman, M.D. Department of Urology Methodist Hospital Institute for Kidney Stone Disease Indiana University School of Medicine Indianapolis, Indiana Stephen Y. Nakada, M.D. Division of Urology Department of Surgery University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Margaret Sue Pearle, M.D., Ph.D. Department of Urology University of Texas Southwestern Medical Center Dallas, Texas Kemal Sarica, M.D., Ph.D. Department of Urology Memorial Hospital Istanbul, Turkey Christian Türk, M.D., Ph.D. Urology Department Rudolfspital Vienna, Austria J. Stuart Wolf, Jr., M.D. Department of Urology University of Michigan Ann Arbor, MI Consultants: Hanan S. Bell, Ph.D. Patrick M. Florer Diann Glickman, PharmD Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 5 Appendix 4: Article Status Report Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 6 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 7 Appendix 5: Article Extraction Form (continued on next page) Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 8 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 9 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 10 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 11 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 12 Appendix 6: Bibliography of Extracted Articles Sorted by Primary Author (includes Procite number and citation) 15572 Abdel-Khalek, M., Sheir, K., Elsobky, E., Showkey, S., Kenawy, M. Prognostic factors for extracorporeal shock-wave lithotripsy of ureteric stones--A multivariate analysis study. Scandinavian Journal of Urology & Nephrology. 2003; 37: 413-8 15606 Aghamir, S. K., Mohseni, M. G., Ardestani, A. Treatment of ureteral calculi with ballistic lithotripsy. Journal of Endourology. 2003; 17: 887-90 17128 Akhtar, M. S., Akhtar, F. K. Utility of the Lithoclast in the treatment of upper, middle and lower ureteric calculi. Surgeon Journal of the Royal Colleges of Surgeons of Edinburgh & Ireland. 2003; 1: 144-8 19854 Akhtar, S., Ather, M. H. Appropriate cutoff for treatment of distal ureteral stones by single session in situ extracorporeal shock wave lithotripsy. Urology. 2005; 66: 1165-8 7686 al Busaidy, S.S., Prem, A.R., Medhat, M. Paediatric ureteroscopy for ureteric calculi: a 4-year experience British Journal of Urology. 1997; 80: 797-801 8030 al Busaidy, S.S., Prem, A.R., Medhat, M., Giriraj, D., Gopakumar, P., Bhat, H.S. Paediatric ureteric calculi: efficacy of primary in situ extracorporeal shock wave lithotripsy British Journal of Urology. 1998; 82: 90-96 18958 Albala, D. M., Siddiqui, K. M., Fulmer, B., Alioto, J., Frankel, J., Monga, M. Extracorporeal shock wave lithotripsy with a transportable electrohydraulic lithotripter: experience with >300 patients. BJU International. 2005; 96: 603-7 16046 Al-Busaidy, S. S., Prem, A. R., Medhat, M., Al-Bulushi, Y. H. Ureteric calculi in children: Preliminary experience with holmium:yag laser lithotripsy. BJU International. 2004; 93: 1318-23 6472 Al-Rasheed, S.A., el-Faqih, S.R., Husain, I., Abdurrahman, M., al-Mugeirin, M.M. The aetiological and clinical pattern of childhood urolithiasis in Saudi Arabia International Urology & Nephrology. 1995; 27: 349-355 16616 Anagnostou, T., Tolley, D. Management of ureteric stones. [Review] [64 refs] European Urology. 2004; 45: 714-21 10696 Andreoni, C., Afane, J., Olweny, E., Clayman, R. V. Flexible ureteroscopic lithotripsy: first-line therapy for proximal ureteral and renal calculi in the morbidly obese and superobese patient Journal of Endourology. 2001; 15: 493-8 15872 Ansari, M. S., Gupta, N. P., Seth, A., Hemal, A. K., Dogra, P. N., Singh, T. P. Stone fragility: its therapeutic implications in shock wave lithotripsy of upper urinary tract stones. International Urology & Nephrology. 2003; 35: 387-92 18154 Aridogan, I. A., Zeren, S., Bayazit, Y., Soyupak, B., Doran, S. Complications of pneumatic ureterolithotripsy in the early postoperative period. Journal of Endourology. 2005; 19: 50-3 14430 Arrabal-Martin, M., Pareja-Vilches, M., Gutierrez-Tejero, F., Mijan-Ortiz, J. L., Palao-Yago, F., Zuluaga-Gomez, A. Therapeutic options in lithiasis of the lumbar ureter. European Urology. 2003; 43: 556-63 9598 Ather, M.H., Memon, A. 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Holmium laser lithotripsy for ureteral calculi: an outpatient procedure Journal of Endourology. 1998; 12: 241-246 7047 Yiu, M.K., Liu, P.L., Yiu, T.F., Chan, A.Y. Clinical experience with holmium:YAG laser lithotripsy of ureteral calculi Lasers In Surgery & Medicine. 1996; 19: 103-106 11132 Zargooshi, J. Open stone surgery in children: is it justified in the era of minimally invasive therapies? Bju International. 2001; 88: 928-31 14424 Zeng, G. Q., Zhong, W. D., Cai, Y. B., Dai, Q. S., Hu, J. B., Wei, H. A. Extracorporeal shock-wave versus pneumatic ureteroscopic lithotripsy in treatment of lower ureteral calculi. Asian Journal of Andrology. 2002; 4: 303-5 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 32 Appendix 7: Bibliography of Extracted Articles Sorted by ProCite Number 6359 Francesca, F., Grasso, M., Da Pozzo, L., Bertini, R., Nava, L., Rigatti, P. Ureteral Lithiasis: In situ Piezoelectric versus in situ spark gap lithotripsy. A randomized study. Archivos Espanoles De Urologia. ; 48: 6420 Erhard, M., Salwen, J., Bagley, D.H. Ureteroscopic removal of mid and proximal ureteral calculi. Journal of Urology. ; 155: 38-42 6425 Ozgur, S., Erol, A., Gunes, Z., Dalva, I., Cetin, S. Predictive value of a new scoring system for the outcome of primary in situ experimental extracorporeal shock wave lithotripsy of upper ureteral calculi. European 6440 Scarpa, R.M., De Lisa, A., Porru, D., Canetto, A., Usai, E. Ureterolithotripsy in children. Urology. ; 46: 8596443 Nakada, S.Y., Pearle, M.S., Soble, J.J., Gardner, S.M., McClennan, B.L., Clayman, R.V. Extracorporeal shock-wave lithotripsy of middle ureteral stones: are ureteral stents necessary?. Urology. ; 46: 649-652 6448 Francesca, F., Scattoni, V., Nava, L., Pompa, P., Grasso, M., Rigatti, P. Failures and complications of transurethral ureteroscopy in 297 cases: conventional rigid instruments vs. small caliber semirigid ureteroscopes. European Urology. ; 28: 112-115 6451 Laerum, E., Ommundsen, O.E., Gronseth, J.E., Christiansen, A., Fagertun, H.E. Oral diclofenac in the prophylactic treatment of recurrent renal colic. A double-blind comparison with placebo. European Urology. ; 6472 Al-Rasheed, S.A., el-Faqih, S.R., Husain, I., Abdurrahman, M., al-Mugeirin, M.M. The aetiological and clinical pattern of childhood urolithiasis in Saudi Arabia. International Urology & Nephrology. ; 27: 349-355 6480 Gade, J., Holtveg, H., Nielsen, O.S., Rasmussen, O.V. The treatment of ureteric calculi before and after the introduction of extracorporeal shockwave lithotripsy. Scandinavian Journal of Urology & Nephrology. ; 29: 6481 Haupt, G., Pannek, J., Herde, T., Schulze, H., Senge, T. The Lithovac: new suction device for the Swiss Lithoclast. Journal of Endourology. ; 9: 375-377 6490 Thuroff, S., Chaussy, C.G. First clinical experience and in situ treatment of ureteric stones using Lithostar Multiline lithotripter. Journal of Endourology. ; 9: 367-370 6504 Scarpa, R.M., De Lisa, A., Usai, E. Diagnosis and treatment of ureteral calculi during pregnancy with rigid ureteroscopes. Journal of Urology. ; 155: 875-877 6505 Schmidt, A., Volz, C., Eisenberger, F. The Dornier Lithotripter U 30: first clinical experience. Journal of Endourology. ; 9: 363-366 6656 Carringer, M., Swartz, R., Johansson, J.E. Management of ureteric calculi during pregnancy by ureteroscopy and laser lithotripsy. British Journal of Urology. ; 77: 17-20 6676 Kumar, V., Ahlawat, R., Banjeree, G.K., Bhaduria, R.P., Elhence, A., Bhandari, M. Percutaneous ureterolitholapaxy: the best bet to clear large bulk impacted upper ureteral calculi. Archivos Espanoles De 6692 Smith, D.P., Jerkins, G.R., Noe, H.N. Urethroscopy in small neonates with posterior urethral valves and ureteroscopy in children with ureteral calculi. Urology. ; 47: 908-910 6701 Lim, D.J., Walker, R.D., Ellsworth, P.I., Newman, R.C., Cohen, M.S., Barraza, M.A., Stevens, P.S. Treatment of pediatric urolithiasis between 1984 and 1994. Journal of Urology. ; 156: 702-705 6716 Grasso, M. Experience with the holmium laser as an endoscopic lithotrite. Urology. ; 48: 199-206 6736 Razvi, H.A., Denstedt, J.D., Chun, S.S., Sales, J.L. Intracorporeal lithotripsy with the holmium:YAG laser. Journal of Urology. ; 156: 912-914 6757 Hosking, D.H., Bard, R.J. Ureteroscopy with intravenous sedation for treatment of distal ureteral calculi: a safe and effective alternative to shock wave lithotripsy. Journal of Urology. ; 156: 899-902 6899 Schow, D.A., Jackson, T.L., Samson, J.M., Hightower, S.A., Johnson, D.L. Use of intravenous alfentanilmidazolam anesthesia for sedation during brief endourologic procedures. Journal of Endourology. ; 8: 33-36 6947 Colombo, T., Zigeuner, R., Altziebler, S., Pummer, K., Stettner, H., Hubmer, G. Effect of extracorporeal shock wave lithotripsy on prostate specific antigen. Journal of Urology. ; 156: 1682-1684 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 33 6957 Elashry, O.M., DiMeglio, R.B., Nakada, S.Y., McDougall, E.M., Clayman, R.V. Intracorporeal electrohydraulic lithotripsy of ureteral and renal calculi using small caliber (1.9F) electrohydraulic lithotripsy probes. Journal of Urology. ; 156: 1581-1585 6960 Geist, E., Schmidt, A., Volz, C., Eisenberger, F. The Dornier-Lithotripter U30. First clinical experience. Archivos Espanoles De Urologia. ; 49: 437-441 6962 Gschwend, J.E., Haag, U., Hollmer, S., Kleinschmidt, K., Hautmann, R.E. Impact of extracorporeal shock wave lithotripsy in pediatric patients: complications and long-term follow-up. Urologia Internationalis. ; 56: 6981 Terai, A., Takeuchi, H., Terachi, T., Kawakita, M., Okada, Y., Yoshida, H., Isokawa, Y., Taki, Y., Yoshida, O. Intracorporeal lithotripsy with the Swiss Lithoclast. International Journal of Urology. ; 3: 184-186 7047 Yiu, M.K., Liu, P.L., Yiu, T.F., Chan, A.Y. Clinical experience with holmium:YAG laser lithotripsy of ureteral calculi. Lasers In Surgery & Medicine. ; 19: 103-106 7096 Cranidis, A.I., Karayannis, A.A., Delakas, D.S., Livadas, C.E., Anezinis, P.E. Cystine stones: the efficacy of percutaneous and shock wave lithotripsy. Urologia Internationalis. ; 56: 180-183 7100 Deliveliotis, C., Kostakopoulos, A., Stavropoulos, N.J., Koutsokalis, G., Dimopoulos, C. Extracorporeal shock wave lithotripsy of middle ureteral calculi: ventral shock wave application. Urologia Internationalis. ; 56: 21-22 7111 Goethuys, H., Winnepenninckx, B., Van Poppel, H., Baert, L. The new generation Siemens Multiline lithotripter tube M: early results in ureteral calculi. Journal of Endourology. ; 10: 403-406 7124 Jung, P., Wolff, J.M., Mattelaer, P., Jakse, G. Role of lasertripsy in the management of ureteral calculi: experience with alexandrite laser system in 232 patients. Journal of Endourology. ; 10: 345-348 7129 Kurzrock, E.A., Huffman, J.L., Hardy, B.E., Fugelso, P. Endoscopic treatment of pediatric urolithiasis. Journal of Pediatric Surgery. ; 31: 1413-1416 7140 Micali, S., Moore, R.G., Averch, T.D., Adams, J.B., Kavoussi, L.R. The role of laparoscopy in the treatment of renal and ureteral calculi. Journal of Urology. ; 157: 463-466 7162 Shroff, S., Watson, G.M., Parikh, A., Thomas, R., Soonawalla, P.F., Pope, A. The holmium: YAG laser for ureteric stones. British Journal of Urology. ; 78: 836-839 7170 Wolf, J.S., Jr., Bub, W.L., Endicott, R.C., Clayman, R.V. Use of intravenous contrast material during in situ extracorporeal shock wave lithotripsy of ureteral calculi. Journal of Urology. ; 157: 38-41 7184 Cass, A.S. Comparison of first-generation (Dornier HM3) and second-generation (Medstone STS) lithotripters: treatment results with 145 renal and ureteral calculi in children. Journal of Endourology. ; 10: 493-499 7187 Deliveliotis, C., Giannakopoulos, S., Louras, G., Koutsokalis, G., Alivizatos, G., Kostakopoulos, A. Doublepigtail stents for distal ureteral calculi: an alternative form of definitive treatment. Urologia Internationalis. ; 7198 Kim, H.H., Lee, J.H., Park, M.S., Lee, S.E., Kim, S.W. In situ extracorporeal shockwave lithotripsy for ureteral calculi: investigation of factors influencing stone fragmentation and appropriate number of sessions for changing treatment modality. Journal of Endourology. ; 10: 501-505 7227 Singal, R.K., Denstedt, J.D. Contemporary management of ureteral stones.. Urologic Clinics of North America. ; 24: 59-70 7260 D'Amico, F.C., Belis, J.A. Treatment of ureteral calculi with an 8.3-Fr. disposable shaft rigid ureteroscope. Techniques in Urology. ; 2: 126-129 7368 Deliveliotis, C., Stavropoulos, N.I., Koutsokalis, G., Kostakopoulos, A., Dimopoulos, C. Distal ureteral calculi: ureteroscopy vs. ESWL. A prospective analysis. International Urology & Nephrology. ; 28: 627-631 7398 Kostakopoulos, A., Stavropoulos, N.J., Louras, G., Deliveliotis, C., Dimopoulos, C. Extracorporeal shock wave lithotripsy of radiolucent urinary calculi using the Dornier HM-3 and HM-4 lithotriptors. Urologia Internationalis. ; 58: 47-49 7408 Miroglu, C., Saporta, L. Transurethral ureteroscopy: is local anesthesia with intravenous sedation sufficiently effective and safe?. European Urology. ; 31: 36-39 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 34 7416 Patel, A., Fuchs, G.J. Expanding the horizons of SWL through adjunctive use of retrograde intrarenal surgery: new techniques and indications. Journal of Endourology. ; 11: 33-36 7441 Yang, S.S., Hong, J.S. Electrohydraulic lithotripsy of upper ureteral calculi with semirigid ureteroscope. Journal of Endourology. ; 10: 27-30 7447 Netto, N.R., Claro, J.A., Esteves, S.C., Andrade, E.F. Ureteroscopic stone removal in the distal ureter. Why change?. Journal of Urology. ; 157: 2081-2083 7469 Kim, S.C., Moon, Y.T. Experience with EDAP LT02 extracorporeal shockwave lithotripsy in 1363 patients: comparison with results of LT01 SWL in 1586 patients. Journal of Endourology. ; 11: 103-111 7478 Minevich, E., Rousseau, M.B., Wacksman, J., Lewis, A.G., Sheldon, C.A. Pediatric ureteroscopy: technique and preliminary results. Journal of Pediatric Surgery. ; 32: 571-574 7488 Tawfiek, E.R., Grasso, M., Bagley, D.H. Initial use of Browne Pneumatic Impactor. Journal of Endourology. ; 11: 121-124 7517 Doublet, J.D., Tchala, K., Tligui, M., Ciofu, C., Gattegno, B., Thibault, P. In situ extracorporeal shock wave lithotripsy for acute renal colic due to obstructing ureteral stones. Scandinavian Journal of Urology & 7521 Denstedt, J.D., Chun, S.S., Miller, M.D., Eberwein, P.M. Intracorporeal lithotripsy with the Alexandrite laser. Lasers In Surgery & Medicine. ; 20: 433-436 7532 Pearle, M.S., McClennan, B.L., Roehrborn, C.G., Clayman, R.V. Bolus injection v drip infusion contrast administration for ureteral stone targeting during shockwave lithotripsy. Journal of Endourology. ; 11: 1637561 Kostakopoulos, A., Stavropoulos, N.I., Louras, G., Deliveliotis, C., Dimopoulos, C. Experience in 3,500 patients with urinary stones treated with the Dornier HM-4 bath-free lithotriptor. International Urology & 7594 Oktay, B., Yavascaoglu, I., Simsek, U., Ozyurt, M. Intracorporeal pneumatic lithotripsy for ureteral and vesical calculi. Scandinavian Journal of Urology & Nephrology. ; 31: 333-336 7599 Teichman, J.M., Rao, R.D., Rogenes, V.J., Harris, J.M. Ureteroscopic management of ureteral calculi: electrohydraulic versus holmium:YAG lithotripsy. Journal of Urology. ; 158: 1357-1361 7632 Segura, J.W., Preminger, G.M., Assimos, D.G., Dretler, S.P., Kahn, R.I., Lingeman, J.E., Macaluso, J.N., Jr. Ureteral Stones Clinical Guidelines Panel summary report on the management of ureteral calculi. Journal of Urology. ; 158: 1915-1921 7665 Bichler, K.H., Lahme, S., Strohmaier, W.L. Indications for open stone removal of urinary calculi. Urologia Internationalis. ; 59: 102-108 7682 Singal, R.K., Razvi, H.A., Denstedt, J.D. Secondary ureteroscopy: results and management strategy at a referral center. Journal of Urology. ; 159: 52-55 7686 al Busaidy, S.S., Prem, A.R., Medhat, M. Paediatric ureteroscopy for ureteric calculi: a 4-year experience. British Journal of Urology. ; 80: 797-801 7725 Mathes, G.L., Jr., Mathes, L.T. High-energy v low-energy shockwave lithotripsy in treatment of ureteral calculi. Journal of Endourology. ; 11: 319-321 7727 Murthy, P.V., Rao, H.S., Meherwade, S., Rao, P.V., Srivastava, A., Sasidharan, K. Ureteroscopic lithotripsy using mini-endoscope and Swiss lithoclast: experience in 147 cases. Journal of Endourology. ; 11: 327-330 7730 Osti, A.H., Hofmockel, G., Frohmuller, H. Ureteroscopic treatment of ureteral stones: only an auxiliary measure of extracorporeal shockwave lithotripsy or a primary therapeutic option?. Urologia Internationalis. ; 7733 Pearle, M.S., Sech, S.M., Cobb, C.G., Riley, J.R., Clark, P.J., Preminger, G.M., Drach, G.W., Roehrborn, C.G. Safety and efficacy of the Alexandrite laser for the treatment of renal and ureteral calculi. Urology. ; 51: 337742 Sinha, R., Sharma, N. Retroperitoneal laparoscopic management of urolithiasis. Journal of Laparoendoscopic and Advanced Surgical Techniques. Part A. ; 7: 95-98 7775 Roberts, W.W., Cadeddu, J.A., Micali, S., Kavoussi, L.R., Moore, R.G. Ureteral stricture formation after removal of impacted calculi. Journal of Urology. ; 159: 723-726 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 35 7781 Bierkens, A.F., Hendrikx, A.J., De La Rosette, J.J., Stultiens, G.N., Beerlage, H.P., Arends, A.J., Debruyne, F.M. Treatment of mid- and lower ureteric calculi: extracorporeal shock-wave lithotripsy vs laser ureteroscopy. A comparison of costs, morbidity and effectiveness. British Journal of Urology. ; 81: 31-35 7805 Daehlin, L., Hellang, M., Ulvik, N.M. Shock wave lithotripsy of urinary calculi with Lithocut C-3000 in a small center. International Urology & Nephrology. ; 29: 617-621 7858 Gould, D.L. Holmium:YAG laser and its use in the treatment of urolithiasis: our first 160 cases. Journal of Endourology. ; 12: 23-26 7863 Hamano, S., Tanaka, M., Suzuki, N., Shiomi, K., Igarashi, T., Murakami, S. Transurethral ureterolithotomy in 100 lower ureteral stones. Urologia Internationalis. ; 60: 53-55 7882 Nazli, O., Cal, C., Ozyurt, C., Gunaydin, G., Cureklibatir, I., Avcieri, V., Erhan, O. Results of extracorporeal shock wave lithotripsy in the pediatric age group. European Urology. ; 33: 333-336 7883 Nguyen, T.A., Belis, J.A. Endoscopic management of urolithiasis in the morbidly obese patient. Journal of Endourology. ; 12: 33-35 7909 Turk, I., Deger, S., Roigas, J., Fahlenkamp, D., Schonberger, B., Loening, S.A. Laparoscopic ureterolithotomy. Techniques in Urology. ; 4: 29-34 8008 Shokeir, A.A., Mutabagani, H. Rigid ureteroscopy in pregnant women. British Journal of Urology. ; 81: 678-681 8013 Teh, C.L., Zhong, P., Preminger, G.M. Laboratory and clinical assessment of pneumatically driven intracorporeal lithotripsy. Journal of Endourology. ; 12: 163-169 8030 al Busaidy, S.S., Prem, A.R., Medhat, M., Giriraj, D., Gopakumar, P., Bhat, H.S. Paediatric ureteric calculi: efficacy of primary in situ extracorporeal shock wave lithotripsy. British Journal of Urology. ; 82: 90-96 8036 Ghobish, A. In situ extracorporeal shockwave lithotripsy of middle and lower ureteral stones: a boosted, stentless, ventral technique. European Urology. ; 34: 93-98 8066 Harmon, W.J., Sershon, P.D., Blute, M.L., Patterson, D.E., Segura, J.W. Ureteroscopy: current practice and long-term complications.. Journal of Urology. ; 157: 28-32 8084 Huang, S., Patel, H., Bellman, G.C. Cost effectiveness of electrohydraulic lithotripsy v Candela pulsed-dye laser in management of the distal ureteral stone. Journal of Endourology. ; 12: 237-240 8106 Vorreuther, R., Klotz, T., Heidenreich, A., Nayal, W., Engelmann, U. Pneumatic v electrokinetic lithotripsy in treatment of ureteral stones. Journal of Endourology. ; 12: 233-236 8109 Yip, K.H., Lee, C.W., Tam, P.C. Holmium laser lithotripsy for ureteral calculi: an outpatient procedure. Journal of Endourology. ; 12: 241-246 8132 Devarajan, R., Ashraf, M., Beck, R.O., Lemberger, R.J., Taylor, M.C. Holmium: YAG lasertripsy for ureteric calculi: an experience of 300 procedures. British Journal of Urology. ; 82: 342-347 8134 Eden, C.G., Mark, I.R., Gupta, R.R., Eastman, J., Shrotri, N.C., Tiptaft, R.C. Intracorporeal or extracorporeal lithotripsy for distal ureteral calculi? Effect of stone size and multiplicity on success rates. Journal of 8164 Tan, P.K., Tan, S.M., Consigliere, D. Ureteroscopic lithoclast lithotripsy: a cost-effective option. Journal of Endourology. ; 12: 341-344 8242 du Fosse, W., Billiet, I., Mattelaer, J. Ureteroscopic treatment of ureteric lithiasis. Analysis of 354 urs procedures in a community hospital. Acta Urologica Belgica. ; 66: 33-40 8255 Kupeli, B., Biri, H., Isen, K., Onaran, M., Alkibay, T., Karaoglan, U., Bozkirli, I. Treatment of ureteral stones: comparison of extracorporeal shock wave lithotripsy and endourologic alternatives. European Urology. ; 34: 8299 Mugiya, S., Ohhira, T., Un-No, T., Takayama, T., Suzuki, K., Fujita, K. Endoscopic management of upper urinary tract disease using a 200-microm holmium laser fiber: initial experience in Japan. Urology. ; 53: 608300 Niall, O., Russell, J., MacGregor, R., Duncan, H., Mullins, J. A comparison of noncontrast computerized tomography with excretory urography in the assessment of acute flank pain. Journal of Urology. ; 161: 534-537 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 36 8307 Tawfiek, E.R., Bagley, D.H. Management of upper urinary tract calculi with ureteroscopic techniques. Urology. ; 53: 25-31 8310 Wong, M.Y. Evolving technique of percutaneous nephrolithotomy in a developing country: Singapore General Hospital experience. Journal of Endourology. ; 12: 397-401 8316 Larkin, G.L., Peacock, W.F., Pearl, S.M., Blair, G.A., D'Amico, F. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. American Journal of Emergency Medicine. ; 17: 6-10 8363 Hosking, D.H., McColm, S.E., Smith, W.E. Is stenting following ureteroscopy for removal of distal ureteral calculi necessary?. Journal of Urology. ; 161: 48-50 8376 Turk, T.M., Jenkins, A.D. A comparison of ureteroscopy to in situ extracorporeal shock wave lithotripsy for the treatment of distal ureteral calculi. Journal of Urology. ; 161: 45-47 8383 Elashry, O.M., Elbahnasy, A.M., Rao, G.S., Nakada, S.Y., Clayman, R.V. Flexible ureteroscopy: Washington University experience with the 9.3F and 7.5F flexible ureteroscopes.. Journal of Urology. ; 157: 2074-2080 8398 Grasso, M., Bagley, D. Small diameter, actively deflectable, flexible ureteropyeloscopy.. Journal of Urology. ; 160: 1648-1654 8454 Beaghler, M., Poon, M., Ruckle, H., Stewart, S., Weil, D. Complications employing the holmium:YAG laser. Journal of Endourology. ; 12: 533-535 8472 Knispel, H.H., Klan, R., Heicappell, R., Miller, K. Pneumatic lithotripsy applied through deflected working channel of miniureteroscope: results in 143 patients. Journal of Endourology. ; 12: 513-515 8477 Lopez-Alcina, E., Broseta, E., Oliver, F., Boronat, F., Jimenez-Cruz, J.F. Paraureteral extrusion of calculi after endoscopic pulsed-dye laser lithotripsy. Journal of Endourology. ; 12: 517-521 8479 Park, H., Park, M., Park, T. Two-year experience with ureteral stones: extracorporeal shockwave lithotripsy v ureteroscopic manipulation. Journal of Endourology. ; 12: 501-504 8481 Reiter, W.J., Schon-Pernerstorfer, H., Dorfinger, K., Hofbauer, J., Marberger, M. Frequency of urolithiasis in individuals seropositive for human immunodeficiency virus treated with indinavir is higher than previously assumed. Journal of Urology. ; 161: 1082-1084 8504 Ferraro, R.F., Abraham, V.E., Cohen, T.D., Preminger, G.M. A new generation of semirigid fiberoptic ureteroscopes. Journal of Endourology. ; 13: 35-40 8517 Mahmood, N., Turner, W., Rowgaski, K., Almond, D. The patients perspective of extracorporeal shock wave lithotripsy. International Urology & Nephrology. ; 30: 671-675 8523 Rhee, B.K., Bretan, P.N., Jr., Stoller, M.L. Urolithiasis in renal and combined pancreas/renal transplant recipients. Journal of Urology. ; 161: 1458-1462 8527 Scarpa, R.M., De Lisa, A., Porru, D., Usai, E. Holmium:YAG laser ureterolithotripsy. European Urology. ; 35: 8559 Biri, H., Kupeli, B., Isen, K., Sinik, Z., Karaoglan, U., Bozkirli, I. Treatment of lower ureteral stones: extracorporeal shockwave lithotripsy or intracorporeal lithotripsy?. Journal of Endourology. ; 13: 77-81 8660 Motola, J.A., Smith, A.D. Complications of ureteroscopy: prevention and treatment. AUA Update Series, 11:162, lesson 21. ; : 8697 Pardalidis, N.P., Kosmaoglou, E.V., Kapotis, C.G. Endoscopy vs. extracorporeal shockwave lithotripsy in the treatment of distal ureteral stones: ten years' experience. Journal of Endourology. ; 13: 161-164 8701 Robert, M., Rakotomalala, E., Delbos, O., Navratil, H. Piezoelectric lithotripsy of ureteral stones: influence of shockwave frequency on sedation and therapeutic efficiency. Journal of Endourology. ; 13: 157-160 8771 Puppo, P., Ricciotti, G., Bozzo, W., Introini, C. Primary endoscopic treatment of ureteric calculi. A review of 378 cases. European Urology. ; 36: 48-52 8788 Miller, O.F., Kane, C.J. Time to stone passage for observed ureteral calculi: a guide for patient education. Journal of Urology. ; 162: 688-691 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 37 8793 Bendhack, M.L., Grimm, M.O., Ackermann, R., Vogeli, T. Primary treatment of ureteral stones by new multiline lithotripter. Journal of Endourology. ; 13: 339-342 8800 Fraser, M., Joyce, A.D., Thomas, D.F., Eardley, I., Clark, P.B. Minimally invasive treatment of urinary tract calculi in children. BJU International. ; 84: 339-342 8805 Jayanthi, V.R., Arnold, P.M., Koff, S.A. Strategies for managing upper tract calculi in young children. Journal of Urology. ; 162: 1234-1237 8806 Joshi, H.B., Obadeyi, O.O., Rao, P.N. A comparative analysis of nephrostomy, JJ stent and urgent in situ extracorporeal shock wave lithotripsy for obstructing ureteric stones. BJU International. ; 84: 264-269 8807 Keeley, F.X., Jr., Pillai, M., Smith, G., Chrisofos, M., Tolley, D.A. Electrokinetic lithotripsy: safety, efficacy and limitations of a new form of ballistic lithotripsy. BJU International. ; 84: 261-263 8812 Menezes, P., Dickinson, A., Timoney, A.G. Flexible ureterorenoscopy for the treatment of refractory upper urinary tract stones. BJU International. ; 84: 257-260 8818 Richter, S., Shalev, M., Lobik, L., Buchumensky, V., Nissenkorn, I. Early postureteroscopy vesicoureteral reflux--a temporary and infrequent complication: prospective study. Journal of Endourology. ; 13: 365-366 8840 Karod, J.W., Danella, J., Mowad, J.J. Routine radiologic surveillance for obstruction is not required in asymptomatic patients after ureteroscopy. Journal of Endourology. ; 13: 433-436 8841 Maheshwari, P.N., Oswal, A.T., ankar, M., Nanjappa, K.M., Bansal, M. Is antegrade ureteroscopy better than retrograde ureteroscopy for impacted large upper ureteral calculi?. Journal of Endourology. ; 13: 441-444 8847 Robert, M., Lanfrey, P., Rey, G., Guiter, J., Navratil, H. Analgesia in piezoelectric SWL: comparative study of kidney and upper ureter treatments. Journal of Endourology. ; 13: 391-395 8948 Peschel, R., Janetschek, G., Bartsch, G. Extracorporeal shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective randomized study [see comments]. Journal of Urology. ; 162: 1909-1912 8956 Kourambas, J., Delvecchio, F. C., Preminger, G. M. Low-power holmium laser for the management of urinary tract calculi, structures, and tumors. Journal of Endourology. ; 15: 529-32 9001 Reddy, P.P., Barrieras, D.J., Bagli, D.J., McLorie, G.A., Khoury, A.E., Merguerian, P.A. Initial experience with endoscopic holmium laser lithotripsy for pediatric urolithiasis. Journal of Urology. ; 162: 1714-1716 9013 Wollin, T.A., Teichman, J.M., Rogenes, V.J., Razvi, H.A., Denstedt, J.D., Grasso, M. Holmium:YAG lithotripsy in children. Journal of Urology. ; 162: 1717-1720 9036 Gnanapragasam, V.J., Ramsden, P.D., Murthy, L.S., Thomas, D.J. 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Journal of Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 47 18154 Aridogan, I. A., Zeren, S., Bayazit, Y., Soyupak, B., Doran, S. Complications of pneumatic ureterolithotripsy in the early postoperative period.. Journal of Endourology. ; 19: 50-3 18174 Kravchick, S., Bunkin, I., Stepnov, E., Peled, R., Agulansky, L., Cytron, S. Emergency extracorporeal shockwave lithotripsy for acute renal colic caused by upper urinary-tract stones.. Journal of Endourology. ; 19: 18204 Yilmaz, E., Batislam, E., Basar, M. M., Tuglu, D., Ferhat, M., Basar, H. The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones.. Journal of Urology. ; 173: 2010-2 18376 Unsal, A., Cimentepe, E., Balbay, M. D. Routine ureteral dilatation is not necessary for ureteroscopy.. 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Journal of 18718 Ng CF, McLornan L, Thompson TJ, Tolley DA Comparison of 2 generations of piezoelectric lithotriptors using matched pair analysis.. Journal of Urology. ; 172: 1887-91 18906 Hsu, J. M., Chen, M., Lin, W. C., Chang, H. K., Yang, S. Ureteroscopic management of sepsis associated with ureteral stone impaction: Is it still contraindicated?.. Urologia Internationalis. ; 74: 319-22 18914 Tan, A. H., Al-Omar, M., Denstedt, J. D., Razvi, H. Ureteroscopy for pediatric urolithiasis: An evolving first-line therapy.. Urology. ; 65: 153-6 18928 Raza, A., Turna, B., Smith, G., Moussa, S., Tolley, D. A. Pediatric urolithiasis: 15 years of local experience with minimally invasive endourological management of pediatric calculi.. Journal of Urology. ; 174: 682-5 18958 Albala, D. M., Siddiqui, K. M., Fulmer, B., Alioto, J., Frankel, J., Monga, M. Extracorporeal shock wave lithotripsy with a transportable electrohydraulic lithotripter: experience with >300 patients.. BJU International. 18970 Hubert, K. C., Palmer, J. S. Passive dilation by ureteral stenting before ureteroscopy: eliminating the need for active dilation.. Journal of Urology. ; 174: 1079-80 18972 Thomas, J. C., DeMarco, R. T., Donohoe, J. M., Adams, M. C., Brock, J. W., 3rd, Pope, J. C, 4th Pediatric ureteroscopic stone management.. Journal of Urology. ; 174: 1072-4 19036 Tombal, B., Mawlawi, H., Feyaerts, A., Wese, F. X., Opsomer, R., Van Cangh, P. J. Prospective randomized evaluation of emergency extracorporeal shock wave lithotripsy (eswl) on the short-time outcome of symptomatic ureteral stones.. European Urology. ; 47: 855-9 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 48 19044 Tiselius, H. G. Removal of ureteral stones with extracorporeal shock wave lithotripsy and ureteroscopic procedures. What can we learn from the literature in terms of results and treatment efforts?.. Urological 19204 Jeon, S. S., Hyun, J. H., Lee, K. S. A comparison of holmium:yag laser with lithoclast lithotripsy in ureteral calculi fragmentation.. International Journal of Urology. ; 12: 544-7 19764 Resim, S., Ekerbicer, H. C., Ciftci, A. Role of tamsulosin in treatment of patients with steinstrasse developing after extracorporeal shock wave lithotripsy.. Urology. ; 66: 945-8 19818 Resim, S., Ekerbicer, H., Ciftci, A. Effect of tamsulosin on the number and intensity of ureteral colic in patients with lower ureteral calculus.. International Journal of Urology. ; 12: 615-20 19854 Akhtar, S., Ather, M. H. Appropriate cutoff for treatment of distal ureteral stones by single session in situ extracorporeal shock wave lithotripsy.. Urology. ; 66: 1165-8 19856 Yilmaz, E., Batislam, E., Basar, M., Tuglu, D., Mert, C., Basar, H. Optimal frequency in extracorporeal shock wave lithotripsy: prospective randomized study.. Urology. ; 66: 1160-4 20034 Wu, C. F., Chen, C. S., Lin, W. Y., Shee, J. J., Lin, C. L., Chen, Y., Huang, W. S. Therapeutic options for proximal ureter stone: extracorporeal shock wave lithotripsy versus semirigid ureterorenoscope with holmium:yttrium-aluminum-garnet laser lithotripsy. Urology. ; 65: 1075-9 Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 49 Appendix 8: Stone Free Rates for Observation Therapies by Size A special analysis of observation therapies was requested for stone sizes of <5, 5-10, and >10 mm stones. Most studies didn’t fit these ranges. Below is the analysis that was possible. Observation Article # # Stone free # pts Notes <5 mm 8788 9526 10632 10828 18522 54 12 9 85 3 68% (46 - 85)% 59 27 9 114 15 8788 10632 10828 8 9 31 47% (36 - 59)% 16 15 73 Meta-analysis: 4mm or less results at 2 weeks 5-10mm Meta-analysis: <10mm - not falling into above classes 9663 19 14548 32 Meta-analysis: 59% (45 - 72)% >10 mm 35 51 >4 mm Results at 1 week no data Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 50 Appendix 9: Stone Free Rates for Medical Therapies by Size A special analysis of medical therapies was requested for stone sizes of <5, 5-10, and >10 mm stones. Most studies didn’t fit these ranges. Below is the analysis that was possible. Active therapies are listed. Most patients also received steroids, nsaids, and/or antibiotics. Medical Therapy Article # # Stone free # pts Notes Nifedipine 9663 16332 16402 Meta-analysis: 31 24 13 74% (55 - 88)% 35 30 25 <10 mm <15 mm Tamsulosin or other alpha blockers as noted 14548 41 51 <10 mm 15156 30 30 18204 23 29 Tamsulosin 18204 22 28 Terazosin 18204 22 29 Doxazosin 18402 68 70 18522 8 15 <5 mm at 2 weeks 19764 24 32 for steinstrasse after SWL Meta-analysis all alpha blocker data 80% (70 - 87)% excluding 19764 81% (70 - 89)% tamsulosin only 82% (69 - 91)% tamsulosin only excluding 19764 84% (69 - 93)% Dual Arm Meta-analysis 8% 25% 27% 25% 27% (-17 - 31)% (16 - 33)% (17 - 36)% (16 - 33)% (17 - 37)% Nifedipine vs. control all alpha blocker data vs. control excluding 19764 vs. control tamsulosin only vs. control tamsulosin only excluding 19764 vs. control Linked Meta-analysis 18% (-9 - 42)% 20% (-7 - 45)% tamsulosin only vs. nifedipine tamsulosin only excluding 19764 vs. nifedipine Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 51 Appendix 10: Complications Graphs Death Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - in situ Distal Ureter >= 10 mm- SWL - all types Distal Ureter >= 10 mm- SWL - in situ Mid Ureter - SWL - all types Mid Ureter - SWL - in situ Mid Ureter - URS - all types Mid Ureter - URS - Flexible Mid Ureter - URS - mixed flexible Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - in situ Mid Ureter >= 10 mm- SWL - all types Mid Ureter >= 10 mm- SWL - in situ Proximal Ureter - SWL - all types Proximal Ureter - SWL - in situ Proximal Ureter - URS - all types Proximal Ureter - URS - Flexible Proximal Ureter - URS - mixed flexible Proximal Ureter <= 10 mm- SWL - all types Proximal Ureter <= 10 mm- SWL - in situ Proximal Ureter >= 10 mm- SWL - all types Proximal Ureter >= 10 mm- SWL - in situ 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 52 80% 100% Transfusion Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - URS - all types Distal Ureter - URS - mixed flexible Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - in situ Distal Ureter >= 10 mm- SWL - all types Distal Ureter >= 10 mm- SWL - in situ Mid Ureter - SWL - all types Mid Ureter - SWL - in situ Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - in situ Mid Ureter >= 10 mm- SWL - all types Mid Ureter >= 10 mm- SWL - in situ Proximal Ureter - URS - all types Proximal Ureter - URS - mixed flexible 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 53 80% 100% Cardiovascular/Pulmonary Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - URS - all types Distal Ureter - URS - rigid Proximal Ureter - SWL - all types Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - mixed flexible 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 54 80% 100% Overall Significant Complications Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - SWL - other Distal Ureter - URS - all types Distal Ureter - URS - mixed flexible Distal Ureter - URS - rigid Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - in situ Distal Ureter <= 10 mm- SWL - other Distal Ureter <= 10 mm- URS - all types Distal Ureter <= 10 mm- URS - rigid Distal Ureter >= 10 mm- SWL - all types Distal Ureter >= 10 mm- SWL - in situ Distal Ureter >= 10 mm- URS - all types Distal Ureter >= 10 mm- URS - rigid Mid Ureter - SWL - all types Mid Ureter - SWL - in situ Mid Ureter - SWL - other Mid Ureter - URS - all types Mid Ureter - URS - Flexible Mid Ureter - URS - mixed flexible Mid Ureter - URS - rigid Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - in situ Mid Ureter <= 10 mm- SWL - other Mid Ureter <= 10 mm- URS - all types Mid Ureter <= 10 mm- URS - rigid Mid Ureter >= 10 mm- URS - all types Mid Ureter >= 10 mm- URS - rigid Proximal Ureter - SWL - all types Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - Flexible Proximal Ureter - URS - mixed flexible Proximal Ureter - URS - rigid Proximal Ureter <= 10 mm- SWL - all types Proximal Ureter <= 10 mm- SWL - in situ Proximal Ureter <= 10 mm- SWL - other Proximal Ureter <= 10 mm- URS - all types Proximal Ureter <= 10 mm- URS - mixed flexible Proximal Ureter <= 10 mm- URS - rigid Proximal Ureter >= 10 mm- SWL - all types Proximal Ureter >= 10 mm- SWL - in situ Proximal Ureter >= 10 mm- URS - all types Proximal Ureter >= 10 mm- URS - mixed flexible Proximal Ureter >= 10 mm- URS - rigid 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 55 80% 100% Sepsis Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - SWL - other Distal Ureter - URS - all types Distal Ureter - URS - mixed flexible Distal Ureter - URS - rigid Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - in situ Distal Ureter <= 10 mm- SWL - other Distal Ureter <= 10 mm- URS - all types Distal Ureter <= 10 mm- URS - rigid Distal Ureter >= 10 mm- SWL - all types Distal Ureter >= 10 mm- SWL - in situ Mid Ureter - SWL - all types Mid Ureter - SWL - in situ Mid Ureter - SWL - other Mid Ureter - URS - all types Mid Ureter - URS - Flexible Mid Ureter - URS - mixed flexible Mid Ureter - URS - rigid Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - other Proximal Ureter - SWL - all types Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - Flexible Proximal Ureter - URS - mixed flexible Proximal Ureter - URS - rigid Proximal Ureter <= 10 mm- SWL - all types Proximal Ureter <= 10 mm- SWL - other Proximal Ureter >= 10 mm- SWL - all types Proximal Ureter >= 10 mm- SWL - in situ Proximal Ureter >= 10 mm- URS - all types Proximal Ureter >= 10 mm- URS - rigid 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 56 80% 100% Steinstrasse Distal Ureter - SWL - All types Distal Ureter - SWL - other Mid Ureter - SWL - All types Mid Ureter - SWL - other Proximal Ureter - SWL - All types Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - mixed flexible 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 57 80% 100% Ureteral Injury Distal Ureter - SWL - All types Distal Ureter - SWL - in situ Distal Ureter - URS - all types Distal Ureter - URS - mixed flexible Distal Ureter - URS - rigid Distal Ureter <= 10 mm- URS - all types Distal Ureter <= 10 mm- URS - rigid Distal Ureter >= 10 mm- URS - all types Distal Ureter >= 10 mm- URS - rigid Mid Ureter - URS - all types Mid Ureter - URS - Flexible Mid Ureter - URS - mixed flexible Mid Ureter - URS - rigid Mid Ureter <= 10 mm- URS - all types Mid Ureter <= 10 mm- URS - rigid Mid Ureter >= 10 mm- URS - all types Mid Ureter >= 10 mm- URS - rigid Proximal Ureter - SWL - All types Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - Flexible Proximal Ureter - URS - mixed flexible Proximal Ureter - URS - rigid Proximal Ureter <= 10 mm- URS - all types Proximal Ureter <= 10 mm- URS - rigid Proximal Ureter >= 10 mm- URS - all types Proximal Ureter >= 10 mm- URS - rigid 0% 20% 40% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 58 60% 80% 100% Ureteral Obstruction Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - SWL - other Distal Ureter - URS - all types Distal Ureter - URS - rigid Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - in situ Distal Ureter <= 10 mm- SWL - other Distal Ureter >= 10 mm- SWL - all types Distal Ureter >= 10 mm- SWL - in situ Mid Ureter - SWL - all types Mid Ureter - SWL - in situ Mid Ureter - SWL - other Mid Ureter - URS - all types Mid Ureter - URS - mixed flexible Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - in situ Mid Ureter <= 10 mm- SWL - other Mid Ureter >= 10 mm- SWL - all types Mid Ureter >= 10 mm- SWL - in situ Proximal Ureter - SWL - all types Proximal Ureter - SWL - bypass Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter <= 10 mm- SWL - all types Proximal Ureter <= 10 mm- SWL - other 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 59 80% 100% UTI Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - SWL - other Distal Ureter - URS - all types Distal Ureter - URS - rigid Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - other Distal Ureter <= 10 mm- URS - all types Distal Ureter <= 10 mm- URS - rigid Mid Ureter - SWL - all types Mid Ureter - SWL - other Mid Ureter - URS - all types Mid Ureter - URS - rigid Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - other Proximal Ureter - SWL - all types Proximal Ureter - SWL - bypass Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - mixed flexible Proximal Ureter - URS - rigid Proximal Ureter <= 10 mm- SWL - all types Proximal Ureter <= 10 mm- SWL - other 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 60 80% 100% Stricture Distal Ureter - SWL - all types Distal Ureter - SWL - in situ Distal Ureter - URS - all types Distal Ureter - URS - mixed flexible Distal Ureter - URS - rigid Distal Ureter <= 10 mm- SWL - all types Distal Ureter <= 10 mm- SWL - in situ Distal Ureter <= 10 mm- URS - all types Distal Ureter <= 10 mm- URS - rigid Distal Ureter >= 10 mm- SWL - all types Distal Ureter >= 10 mm- SWL - in situ Mid Ureter - SWL - all types Mid Ureter - SWL - in situ Mid Ureter - URS - all types Mid Ureter - URS - Flexible Mid Ureter - URS - mixed flexible Mid Ureter - URS - rigid Mid Ureter <= 10 mm- SWL - all types Mid Ureter <= 10 mm- SWL - in situ Mid Ureter >= 10 mm- SWL - all types Mid Ureter >= 10 mm- SWL - in situ Proximal Ureter - SWL - all types Proximal Ureter - SWL - in situ Proximal Ureter - SWL - other Proximal Ureter - URS - all types Proximal Ureter - URS - Flexible Proximal Ureter - URS - mixed flexible Proximal Ureter - URS - rigid Proximal Ureter <= 10 mm- URS - all types Proximal Ureter <= 10 mm- URS - rigid Proximal Ureter >= 10 mm- URS - all types Proximal Ureter >= 10 mm- URS - rigid 0% 20% 40% 60% Estimated Occurrence Rate with 95% CI CI, Confidence Interval Copyright © 2007 American Urological Association Education and Research, Inc.® and European Association of Urology 61 80% 100% References 1. 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