Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 1 of 44
1 Retrograde Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (Short title: RIRS vs. PCNL vs. ESWL for Lower Pole Stones: A Meta-analysis)
Wei Zhang*1, Tie Zhou*1, Tengyun Wu*2, Xiaofeng Gao1, Yonghan Peng1, Chuanliang Xu1, Qi Chen3, Ruixiang Song1, Yinghao Sun1
* These authors contribute equally to this work
1. Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, PR China 2. Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China 3. Department of Health Statistics, Faculty of Health Service, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China
All correspondences should be addressed to Yinghao Sun, MD. PhD. Department of Urology, Changhai Hospital Second Military Medical University 168 Changhai Road Shanghai 200433, PR China E-mail: [email protected]
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 2 of 44
2
Abstract Background: The optimal treatment of lower pole renal stones continues to be a dilemma for urologists. Retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and extracorporeal shock wave lithotripsy (ESWL) all constitute viable therapeutic options in selected patients. The aim of this study was to assess the efficacy and safety of RIRS, PCNL and ESWL in management of lower pole renal stones. Methods: A literature search was performed in July 2014 using PubMed, Embase, and Web of Science databases. Literature reviewed included meta-analysis and randomized and nonrandomized controlled studies to identify relevant studies for the meta-analysis. Results: Six randomized and eight nonrandomized studies were identified for analysis. PCNL provided a significantly higher stone-free rate (SFR) compared with RIRS and ESWL. Furthermore, no statistical significant difference was found when PCNL was compared with RIRS and ESWL for complication rate. Compared to the other two treatments, RIRS had longer operative time and PCNL had longer hospital stay. ESWL was associated with significantly higher retreatment rate compared to RIRS and PCNL, whereas there were no significant differences in auxiliary procedure rates among the three treatment techniques. Conclusion: RIRS offers a relative higher SFR while has a longer operative time. PCNL is associated with the highest SFR at the expense of the longest hospital stay. ESWL is performed as an outpatient procedure with a relative shorter operative time, however, it has lower SFR and higher retreatment rate. The categories of complications vary while the overall complication rates are comparable among the three treatment techniques.
Keywords: Retrograde intrarenal surgery, Percutaneous nephrolithotomy, Extracorporeal shock wave Lithotripsy, Lower pole stone, Meta-analysis
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 3 of 44
3
Introduction With minimally invasive technological advances, retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and extracorporeal shock wave lithotripsy (ESWL) have become standard treatment options for kidney stones. However, the treatment of lower pole stones differs from that of upper and middle pole calculi, because stones in the lower pole have to ascend up the lower pole infundibulum, pass into the renal pelvis, and then exit the kidney down the ureter. Because the lower pole is the most dependent portion and difficulty accessing of the kidney, stones in the lower pole are the most difficult to clear1, 2. The optimal treatment of lower pole calculi continues to be a dilemma which has recently received heightened attention among urologists.
ESWL is a low morbidity outpatient procedure which is preferred by many urologists and accepted by many patients. The 2013 European Association of Urology (EAU) guidelines recommend ESWL as the first treatment option for lower pole renal stones smaller than 1cm3. However, ESWL may be associated with poor clearance of fragments from the lower pole, because its stone-free rate (SFR) is dependent on anatomic features4.
At present, PCNL is the standard option for the treatment of large stones (> 2cm), and is also preferred for the management of multiple renal stones or stones in dependent areas of the kidney such as the lower pole by many urologists, because of its constantly high success rates independent of stone size5. Nevertheless, its high SFR is counterbalanced by the risk of high morbidity rate6. Recently, efforts have been made to decrease the morbidity associated with PCNL. With the emergence of the minimally invasive PCNL applying miniaturized instruments and tubeless technique that reduce the invasiveness of conventional PCNL, a great decreased rate of complications has been achieved without affecting its excellent result7, 8.
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 4 of 44
4
A potentially less invasive alternative to the percutaneous approaches is provided by flexible ureteroscopy, also referred to as RIRS, which was originally applied in the management of lower pole stones resistant to ESWL9. RIRS is increasingly used as a primary modality to treat lower pole stones, and it may potentially achieve higher SFR than ESWL with lower morbidity than PCNL for patients with low volume stone disease. However, the drawbacks of retrograde access include the limited visualisation, reduced size of fragment removal, and the requirement of stone lithotrites and baskets10. What’s more, high cost is a major obstacle to the widely application of RIRS, especially in developing countries10. Regardless of their limitations, PCNL and RIRS are recommended as first-line treatments of lower pole stones on the occasion that anatomic factors make ESWL unfavorable in 2013 EAU guidelines of urolithiasis3.
We aim to perform a meta-analysis of available high-level studies to evaluate the efficacy and safety of RIRS, PCNL and ESWL in the management of lower pole renal stones. The main crucial parameters under evaluation included the efficacy of each method, as described by the SFR, the complication rate, the operative time, the hospital stay, the auxiliary procedure rate and the recurrence rate.
Methods Literature search and article selection A literature search was performed in July 22nd 2014 using PubMed, Embase, and Web of Science databases to identify relevant studies. The following search terms were used for the search: (retrograde intrarenal surgery/flexible ureterorenoscopy/flexible ureteroscopy/RIRS OR percutaneous nephrolithotomy/percutaneous lithotripsy/PCNL OR extracorporeal shock wave lithotripsy/ESWL) AND lower/inferior AND calyceal/calices/calyx. Search restrictions were set for the English language and human species. The retrieved articles were gathered and viewed by W.Z and T.Z independently, and all disagreements were resolved by their consensus. Reference lists of the selected articles retrieved in the search as
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 5 of 44
5 well as relevant review articles were also studied (Fig. 1).
Evaluation of study quality The levels of evidence (LE) were estimated for all included studies using the criteria provided by the Oxford Centre for Evidence Based Medicine11. The methodological quality of the studies was evaluated according to the Jadad Scale for randomized controlled trials (RCTs)12 and the Newcastle-Ottawa Scale (NOS) for nonrandomized controlled trials13. The assessments were processed independently by two reviewers and the final decision was determined by a discussion between them.
Statistical analysis After the studies were reviewed, a meta-analysis was performed to assess the efficacy and safety of RIRS, PCNL and ESWL in management of lower pole renal stones by the pairwise comparisons among the three treatment techniques. Extracted data for the analysis included SFR, postoperative complication rate, operative time, length of hospital stay, need for auxiliary procedures and retreatments. The odds ratio (OR) and mean difference was calculated for the binary and continuous variables, respectively. To perform a meta-analysis of continuous parameters, the mean values and standard deviations are required in order to pool data. Nevertheless, sometimes, the published literatures only present continuous data as means and range. For those studies, standard deviations were calculated according to the methodology described by Hozo et al14.
The Q and I2 statistics were used to evaluate the heterogeneity among studies: Homogeneity was rejected when the Q statistic p value was < 0.10 or the I2 value was > 30%. Depending on whether homogeneity was accepted or rejected, we applied the fixed effect model or the random effect model to estimate the combined ORs (or weighted mean differences) and the 95% confidence intervals (CIs). The pooled effects were computed by the z test, and Statistical significance was set
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 6 of 44
6 at p < 0.05. The statistical analysis was conducted using Stata v.12.0 statistical software (StataCorp, College Station, TX, USA).
Results Study characteristics 14 studies have been finally included for the analysis, composing of six RCTs15-20 (LE: 2b) including four multi-institutional trials and eight retrospective case control studies21-28 (LE: 3b) (Table 1). The methodological quality of included studies was relatively high for three of the nonrandomized studies (NOS: 7 of 9 points and 6 of 9 points) and medium for five (NOS: 5 of 9 points and 4 of 9 points), whereas the five RCTs were medium quality (Jadad Scale: 3 of 5 points) and relatively low for only one (Jadad Scale: 2 of 5 points), which was mainly attributed to the no blind methods.
A total of 328 RIRS cases (15.3%), 476 PCNL cases (22.2%) and 1338 ESWL cases (62.5%) were compared in our meta-analysis. There were two studies comparing all the three treatment techniques21, 22, whereas two comparing RIRS and PCNL23, 24, five comparing RIRS and ESWL15-17, 25, 26, and remaining five comparing PCNL and ESWL18-20, 27, 28. In addition, only two studies mentioned their portion of patients with multiple stones23, 24. Still and all, the preoperative demographic characteristics such as mean age (45.9 vs 44.1 vs 46.7 yr), sex ratio (male/female: 1.5 vs 1.6 vs 1.4), stone location (left/right: 1.0 vs 1.1 vs 1.3) and stone size (1.2 vs 1.6 vs 1.4 cm) were comparable among RIRS, PCNL and ESWL study populations (Table 2).
Meta-analysis outcomes SFR and complication rate PCNL provided a significantly higher SFR compared with RIRS (OR, 0.41; 95% CI, 0.21–0.82; p =0.012) and ESWL (OR, 8.75; 95% CI, 3.29–23.26; p
Page 1 of 44
1 Retrograde Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (Short title: RIRS vs. PCNL vs. ESWL for Lower Pole Stones: A Meta-analysis)
Wei Zhang*1, Tie Zhou*1, Tengyun Wu*2, Xiaofeng Gao1, Yonghan Peng1, Chuanliang Xu1, Qi Chen3, Ruixiang Song1, Yinghao Sun1
* These authors contribute equally to this work
1. Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, PR China 2. Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China 3. Department of Health Statistics, Faculty of Health Service, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China
All correspondences should be addressed to Yinghao Sun, MD. PhD. Department of Urology, Changhai Hospital Second Military Medical University 168 Changhai Road Shanghai 200433, PR China E-mail: [email protected]
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 2 of 44
2
Abstract Background: The optimal treatment of lower pole renal stones continues to be a dilemma for urologists. Retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and extracorporeal shock wave lithotripsy (ESWL) all constitute viable therapeutic options in selected patients. The aim of this study was to assess the efficacy and safety of RIRS, PCNL and ESWL in management of lower pole renal stones. Methods: A literature search was performed in July 2014 using PubMed, Embase, and Web of Science databases. Literature reviewed included meta-analysis and randomized and nonrandomized controlled studies to identify relevant studies for the meta-analysis. Results: Six randomized and eight nonrandomized studies were identified for analysis. PCNL provided a significantly higher stone-free rate (SFR) compared with RIRS and ESWL. Furthermore, no statistical significant difference was found when PCNL was compared with RIRS and ESWL for complication rate. Compared to the other two treatments, RIRS had longer operative time and PCNL had longer hospital stay. ESWL was associated with significantly higher retreatment rate compared to RIRS and PCNL, whereas there were no significant differences in auxiliary procedure rates among the three treatment techniques. Conclusion: RIRS offers a relative higher SFR while has a longer operative time. PCNL is associated with the highest SFR at the expense of the longest hospital stay. ESWL is performed as an outpatient procedure with a relative shorter operative time, however, it has lower SFR and higher retreatment rate. The categories of complications vary while the overall complication rates are comparable among the three treatment techniques.
Keywords: Retrograde intrarenal surgery, Percutaneous nephrolithotomy, Extracorporeal shock wave Lithotripsy, Lower pole stone, Meta-analysis
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 3 of 44
3
Introduction With minimally invasive technological advances, retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and extracorporeal shock wave lithotripsy (ESWL) have become standard treatment options for kidney stones. However, the treatment of lower pole stones differs from that of upper and middle pole calculi, because stones in the lower pole have to ascend up the lower pole infundibulum, pass into the renal pelvis, and then exit the kidney down the ureter. Because the lower pole is the most dependent portion and difficulty accessing of the kidney, stones in the lower pole are the most difficult to clear1, 2. The optimal treatment of lower pole calculi continues to be a dilemma which has recently received heightened attention among urologists.
ESWL is a low morbidity outpatient procedure which is preferred by many urologists and accepted by many patients. The 2013 European Association of Urology (EAU) guidelines recommend ESWL as the first treatment option for lower pole renal stones smaller than 1cm3. However, ESWL may be associated with poor clearance of fragments from the lower pole, because its stone-free rate (SFR) is dependent on anatomic features4.
At present, PCNL is the standard option for the treatment of large stones (> 2cm), and is also preferred for the management of multiple renal stones or stones in dependent areas of the kidney such as the lower pole by many urologists, because of its constantly high success rates independent of stone size5. Nevertheless, its high SFR is counterbalanced by the risk of high morbidity rate6. Recently, efforts have been made to decrease the morbidity associated with PCNL. With the emergence of the minimally invasive PCNL applying miniaturized instruments and tubeless technique that reduce the invasiveness of conventional PCNL, a great decreased rate of complications has been achieved without affecting its excellent result7, 8.
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 4 of 44
4
A potentially less invasive alternative to the percutaneous approaches is provided by flexible ureteroscopy, also referred to as RIRS, which was originally applied in the management of lower pole stones resistant to ESWL9. RIRS is increasingly used as a primary modality to treat lower pole stones, and it may potentially achieve higher SFR than ESWL with lower morbidity than PCNL for patients with low volume stone disease. However, the drawbacks of retrograde access include the limited visualisation, reduced size of fragment removal, and the requirement of stone lithotrites and baskets10. What’s more, high cost is a major obstacle to the widely application of RIRS, especially in developing countries10. Regardless of their limitations, PCNL and RIRS are recommended as first-line treatments of lower pole stones on the occasion that anatomic factors make ESWL unfavorable in 2013 EAU guidelines of urolithiasis3.
We aim to perform a meta-analysis of available high-level studies to evaluate the efficacy and safety of RIRS, PCNL and ESWL in the management of lower pole renal stones. The main crucial parameters under evaluation included the efficacy of each method, as described by the SFR, the complication rate, the operative time, the hospital stay, the auxiliary procedure rate and the recurrence rate.
Methods Literature search and article selection A literature search was performed in July 22nd 2014 using PubMed, Embase, and Web of Science databases to identify relevant studies. The following search terms were used for the search: (retrograde intrarenal surgery/flexible ureterorenoscopy/flexible ureteroscopy/RIRS OR percutaneous nephrolithotomy/percutaneous lithotripsy/PCNL OR extracorporeal shock wave lithotripsy/ESWL) AND lower/inferior AND calyceal/calices/calyx. Search restrictions were set for the English language and human species. The retrieved articles were gathered and viewed by W.Z and T.Z independently, and all disagreements were resolved by their consensus. Reference lists of the selected articles retrieved in the search as
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 5 of 44
5 well as relevant review articles were also studied (Fig. 1).
Evaluation of study quality The levels of evidence (LE) were estimated for all included studies using the criteria provided by the Oxford Centre for Evidence Based Medicine11. The methodological quality of the studies was evaluated according to the Jadad Scale for randomized controlled trials (RCTs)12 and the Newcastle-Ottawa Scale (NOS) for nonrandomized controlled trials13. The assessments were processed independently by two reviewers and the final decision was determined by a discussion between them.
Statistical analysis After the studies were reviewed, a meta-analysis was performed to assess the efficacy and safety of RIRS, PCNL and ESWL in management of lower pole renal stones by the pairwise comparisons among the three treatment techniques. Extracted data for the analysis included SFR, postoperative complication rate, operative time, length of hospital stay, need for auxiliary procedures and retreatments. The odds ratio (OR) and mean difference was calculated for the binary and continuous variables, respectively. To perform a meta-analysis of continuous parameters, the mean values and standard deviations are required in order to pool data. Nevertheless, sometimes, the published literatures only present continuous data as means and range. For those studies, standard deviations were calculated according to the methodology described by Hozo et al14.
The Q and I2 statistics were used to evaluate the heterogeneity among studies: Homogeneity was rejected when the Q statistic p value was < 0.10 or the I2 value was > 30%. Depending on whether homogeneity was accepted or rejected, we applied the fixed effect model or the random effect model to estimate the combined ORs (or weighted mean differences) and the 95% confidence intervals (CIs). The pooled effects were computed by the z test, and Statistical significance was set
Journal of Endourology Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shock Wave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-analysis and Systematic Review (doi: 10.1089/end. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 6 of 44
6 at p < 0.05. The statistical analysis was conducted using Stata v.12.0 statistical software (StataCorp, College Station, TX, USA).
Results Study characteristics 14 studies have been finally included for the analysis, composing of six RCTs15-20 (LE: 2b) including four multi-institutional trials and eight retrospective case control studies21-28 (LE: 3b) (Table 1). The methodological quality of included studies was relatively high for three of the nonrandomized studies (NOS: 7 of 9 points and 6 of 9 points) and medium for five (NOS: 5 of 9 points and 4 of 9 points), whereas the five RCTs were medium quality (Jadad Scale: 3 of 5 points) and relatively low for only one (Jadad Scale: 2 of 5 points), which was mainly attributed to the no blind methods.
A total of 328 RIRS cases (15.3%), 476 PCNL cases (22.2%) and 1338 ESWL cases (62.5%) were compared in our meta-analysis. There were two studies comparing all the three treatment techniques21, 22, whereas two comparing RIRS and PCNL23, 24, five comparing RIRS and ESWL15-17, 25, 26, and remaining five comparing PCNL and ESWL18-20, 27, 28. In addition, only two studies mentioned their portion of patients with multiple stones23, 24. Still and all, the preoperative demographic characteristics such as mean age (45.9 vs 44.1 vs 46.7 yr), sex ratio (male/female: 1.5 vs 1.6 vs 1.4), stone location (left/right: 1.0 vs 1.1 vs 1.3) and stone size (1.2 vs 1.6 vs 1.4 cm) were comparable among RIRS, PCNL and ESWL study populations (Table 2).
Meta-analysis outcomes SFR and complication rate PCNL provided a significantly higher SFR compared with RIRS (OR, 0.41; 95% CI, 0.21–0.82; p =0.012) and ESWL (OR, 8.75; 95% CI, 3.29–23.26; p
