Pediatric Urology
Slow vs Rapid Delivery Rate Shock Wave Lithotripsy for Pediatric Renal Urolithiasis: A Prospective Randomized Study Hosni Khairy Salem,* Hesham Fathy, Hanny ElFayoumy, Hussein Aly, Ahmed Ghonium, Mostafa A. Mohsen and Abd El Rahim Hegazy From the Urology Department, Faculty of Medicine, Cairo University, Giza, Egypt
Abbreviations and Acronyms KUB ¼ plain x-ray of kidney, ureters and bladder PCNL ¼ percutaneous nephrolithotomy SWL ¼ shock wave lithotripsy Accepted for publication November 13, 2013. Study received institutional review board approval. * Correspondence: Urology Department, Faculty of Medicine, Cairo University, P. O. Box 247, Giza 12515, Egypt (telephone: 201-006042442, 201-001425799; e-mail: [email protected]).
Purpose: We compared slow vs fast shock wave frequency rates in disintegration of pediatric renal stones less than 20 mm. Materials and Methods: Our study included 60 children with solitary 10 to 20 mm radiopaque renal stones treated with shock wave lithotripsy. Patients were prospectively randomized into 2 groups, ie those undergoing lithotripsy at a rate of 80 shock waves per minute (group 1, 30 patients) and those undergoing lithotripsy at a rate of 120 shock waves per minute (group 2, 30 patients). The 2 groups were compared in terms of treatment success, anesthesia time, secondary procedures and efficiency quotient. Results: Stone clearance rate was significantly higher in group 1 (90%) than in group 2 (73.3%, p ¼ 0.025). A total of 18 patients in group 1 (60%) were rendered stone-free after 1 session, 8 required 2 sessions and 1 needed 3 sessions, while shock wave lithotripsy failed in 3 patients. By comparison, 8 patients (26.6%) in group 2 were rendered stone-free after 1 session, 10 (33.3%) required 2 sessions and 4 (13.3%) needed 3 sessions to become stone-free. Mean general anesthesia time was significantly longer in group 1 (p ¼ 0.041). Postoperatively 2 patients in group 1 and 4 in group 2 suffered low grade fever (Clavien grade II). Significantly more secondary procedures (percutaneous nephrolithotomy, repeat shock wave lithotripsy) were required in group 2 (p ¼ 0.005). The predominant stone analysis was calcium oxalate dihydrate in both groups. Efficiency quotient was 0.5869 and 0.3437 for group 1 and group 2, respectively (p ¼ 0.0247). Conclusions: In children with renal stones slow delivery rates of shock wave lithotripsy have better results regarding stone clearance than fast delivery rates. Key Words: high-energy shock waves, kidney calculi, lithotripsy, pediatrics, urolithiasis
UROLITHIASIS constitutes an important part of our practice.1 The introduction of shock wave lithotripsy during the early 1980s dramatically changed the management of urinary tract stones. During the last 2 decades the development of new lithotripters has changed completely the way in which patients with stones are treated.2,3 Epidemiological studies have revealed an increase in the
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incidence of pediatric stones worldwide.4 It is accepted that pediatric patients have increased clearance rate of stones compared to adults.5 Shock wave lithotripsy was first successfully used in children in 1986,6 and is now considered firstline treatment for the management of pediatric stones of the upper urinary tract.7e9 In adults stone disintegration during SWL has been
0022-5347/14/1915-1370/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.11.028 Vol. 191, 1370-1374, May 2014 Printed in U.S.A.
SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
improved by slowing the rate of delivery. Consequently slow rates of SWL have contributed to better treatment options.10,11 Few studies have focused on the relation of the frequency rate of shock wave delivery to renal stone clearance in adults.10e12 To our knowledge no previous study has been published comparing slow vs fast shock wave frequency rates in pediatric urolithiasis except 1 abstract presented in 2001.12 We compared slow and fast shock wave frequency delivery rates in disintegrating pediatric renal stones smaller than 20 mm and the impact on stone clearance. Terms of comparison included treatment success, anesthesia time, secondary procedures, costs and efficiency quotient.
PATIENTS AND METHODS A total of 60 patients with a mean SD age of 5.56 3.54 years (range 3 to 14) presenting with solitary radiopaque renal stones (10 to 20 mm) between August 2011 and July 2012 were included in the study. Patients were recruited from the outpatient clinic and were prospectively randomized (envelope method) into 2 groups. Group 1 consisted of 30 patients undergoing SWL at 80 shock waves per minute and group 2 included 30 patients undergoing SWL at 120 shock waves per minute. We chose these rates based on previous studies using either rate separately in adults, young adults and children, which had proved safe. Also ungated SWL proved to be safe in children. Exclusion criteria consisted of multiple stones, moderate or severe hydronephrosis, active infection, coagulopathy, stone size less than 10 mm or more than 20 mm, bilateral renal stones, radiolucent stones, anatomical abnormality in the ureter or ureteropelvic junction, cardiac pacemaker and uremia. Preoperative imaging included ultrasound, KUB and/or excretory urography. Maximum longitudinal diameter (length) was used to reflect the size of the stone. The study received institutional review board approval, and parents gave informed consent after proper counseling. All selected patients fulfilling the inclusion criteria were treated with SWL using the Dornier Lithotripter S (Dornier Medical Systems, Kennesaw, Georgia) with the 220 electromagnetic shock wave emitter. Fluoroscopy was used for stone localization. The procedure was done with patients under general anesthesia. Intravenous fluids were administered throughout the procedure. All children underwent lithotripsy using the same device with a gradual incremental energy increase from 14 to 20 kV. We usually start by low amplitude initially and increase it gradually from 14 to 24 kV, except that in children younger than 4 years we increase it to only 18 kV to reduce the possibility of renal tissue injuries. Maximum number of shock waves delivered was 2,500, except if complete fragmentation was evident on fluoroscopy screen before reaching 2,500 shock waves. Patients were kept under observation for 3 hours until fully conscious and urine was relatively clear of blood. On
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discharge from the hospital the parents were instructed to maintain adequate fluid intake in their children, in general 1 to 2 cc/kg per hour according to body weight. An analgesic (diclofenac pediatric suppository) was prescribed on discharge home. Parents were also instructed to check for expected hematuria and passage of stone fragments, and to report if the child had a fever or colic. Stone fragments were collected for chemical stone analysis. Patients were reevaluated with KUB and abdominal ultrasound 2 and 4 weeks after the SWL session. Those who had sizable fragments were scheduled for another session 3 weeks later. The maximum number of sessions allowed for our patients was 3. Primary outcome measure was stone-free rate (success rate), while secondary outcome measures included anesthesia time and repeat treatment rate, complications, secondary procedures, cost and efficiency quotient. Stone-free rate was defined as no residual fragments or only 1 clinically insignificant fragment (less than 3 mm, which was nonsymptomatic, noninfectious and nonobstructive) on KUB and ultrasound. Unsuccessful SWL was defined as lack of evidence of disintegration or fragmentation on KUB and ultrasound after 3 SWL sessions. Data were statistically described in terms of mean SD and range, or frequency (number of cases) and percentages when appropriate. Comparison of numerical variables between the 2 groups was done using the Student t-test for independent samples. For comparing categorical data chisquare testing was performed, with the Fisher exact test used when the expected frequency was less than 5. All p values less than 0.05 were considered statistically significant. All statistical calculations were done using SPSSÒ, version 15 for WindowsÒ.
RESULTS Table 1 shows demographic data and outcomes for the 2 groups. The groups were comparable in terms of age, male-to-female ratio, stone size, stone site and total number of shock waves administered. The success rate in group 1 was 90%, with success in 27 patients and failure in 3, compared to a 73.3% success rate in group 2, with success in 22 patients and failure in 8. A total of 18 patients in group 1 were rendered stone-free after 1 session, 8 needed 2 sessions and 1 needed 3 sessions, while SWL failed in 3 patients. By comparison, 8 patients in group 2 required 1 session, 10 required 2 and 4 needed 3 sessions to become stone-free, with 8 failing SWL. Mean time of general anesthesia was significantly longer in group 1 (table 1). Postoperatively 2 patients in group 1 and 4 in group 2 suffered low grade fever (Clavien grade II). Subcapsular hematoma or significant hematuria was not reported in either group. No arrhythmia was detected during SWL sessions. The 11 cases that failed SWL (3 in group 1 and 8 in group 2) subsequently were managed by PCNL. Number of repeat treatments and secondary procedures (PCNL or
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SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
Table 1. Demographic data and treatment outcomes Group 1 No. gender (%): Male Female Mean SD body mass index Mean SD yrs age (range) No. laterality (%): Rt Lt Mean SD stone size (mm) No. site: Pelvis Middle calyx Lower pole Mean SD shock waves Mean anesthesia time (mins) No. success (%): After 1 session After 2 sessions After 3 sessions Total No. secondary procedures: Repeat SWL PCNL No. predominant stone analysis (%): Calcium oxalate monohydrate Calcium oxalate dihydrate Calcium phosphate Mixed calcium oxalate þ calcium phosphate Efficiency quotient Requirement for 30 pts to be stone-free No. sessions/No. pts (mean SD sessions)
Group 2
p Value 0.695
20 10 22.7 5.35 12 18 15.02
(33.3) (66.7) 2.5 3.67 (3e14) (40) (60) 2.47
15 6 9 2,300 150 37.02 18 8 1 27
18 12 23.4 6.67 13 17 13.85
(60.0) (40.0) 3.1 2.94 (3e13)
0.179 0.085 0.546
(43.7) (56.7) 3.42
0.563 0.836
18 7 5 2,450 110 25.43 (60.0) (26.6) (3.3) (90)
8 10 4 22
(10%)
34 8
0.256 0.041 0.025 (26.6) (33.3) (13.3) (73.3) 0.005
16 3
(26.7%) 0.457
5 (16.7) 20 (66.6) 2 (6.6) 3 (9.9) 0.5869 46 SWL sessions (30 primary þ 16 repeat), 3 PCNLs 46/30 (1.53 0.35)
repeat SWL) were significantly greater in group 2 (16 SWL sessions and 3 PCNLs in group 1 vs 34 SWL sessions and 8 PCNLs in group 2). The predominant stone analysis was calcium oxalate dihydrate in both groups (66% in group 1 and 60% in group 2). Efficiency quotient was 0.5869 and 0.3437 for group 1 and group 2, respectively (p ¼ 0.0247), which is statistically significant. Mean SD SWL sessions per patient were significantly greater in group 2 than in group 1 (table 1). Three patients in group 1 failed SWL. Stone sizes in these patients were 1.5, 1.8 and 2.0 cm. All stones were in the pelvis. Two stones consisted of calcium oxalate monohydrate, while 1 was mixed (table 2). Eight patients in group 2 failed SWL. Stone sizes were more than 1.5 cm in 7 cases (range 1.0 to 2). One stone was in the lower pole, 3 were in the middle calyx and 4 were in the pelvis. Five stones were calcium oxalate monohydrate and 3 were calcium oxalate dihydrate (table 2). Regarding first session success for smaller stones (10 to 15 mm), no significant difference was noted between the groups (table 3). For larger stones (15 to 20 mm) the low frequency group had significantly better results. Regarding the first session success in the low frequency group, the results were better for large stones than for small stones. In the high frequency
6 (19.6) 18 (60.5) 4 (13.3) 2 (6.6) 0.3437 64 SWL sessions (30 primary þ 34 repeat), 8 PCNLs 64/30 (2.1 0.25)
0.0247 e 0.0112
group no difference in results was noted between small stones and large stones (table 3).
DISCUSSION Our study included 60 patients presenting with renal stones treated with SWL divided randomly into 2 groups. Group 1 consisted of 30 patients who Table 2. Analysis of treatment failures after 3 sessions
Pt age (yrs) No. gender: Male Female Body mass index No. laterality: Rt Lt No. stone size (mm): 10e15 15e20 No. site/total No.: Pelvis Middle calyx Lower calyx No. sessions No. shock waves No. stone analysis: Calcium oxalate monohydrate Calcium oxalate dihydrate Calcium phosphate Mixed
Group 1
Group 2
5e9
3e10
1 2 12.0e14.0
4 4 18.3e28.5
3 0
3 5
0 3
1 7
3/15 0/6 0/9 3 2,500
4/18 3/7 1/5 3 2,500
2 0 0 1
5 3 0 0
SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
Table 3. First session success according to stone size and site
No. site/total No.: Pelvis Middle calyx Lower calyx No. size(mm)/total No. 10e15 15e20 No. stone analysis: Calcium oxalate monohydrate Calcium oxalate dihydrate Calcium phosphate Mixed
Group 1
Group 2
10/15 5/6 3/9
6/18 1/7 1/5
6/14 12/16
4/16 4/14
2 14 2 0
0 6 0 2
p Value 0.557
0.351 0.0451 0.0244
underwent SWL using 80 shock waves per minute, and group 2 included 30 patients who underwent SWL using 120 shock waves per minute. In group 1 success was observed in 27 patients (90%) and failure occurred in 3, while in group 2 success was observed in 22 patients (73.3%) and failure occurred in 8. The success rate after the first session was significantly higher in group 1 than in group 2 (60.0% vs 26.6%). In the remaining patients the success rate after a second session was 26.6% in group 1 and 33.3% in group 2. For the remainder the success rate after a third session was 3.3% in group 1 and 13.3% in group 2. We found no study in the literature comparing the effect of SWL delivery rates (slow vs fast) in pediatric stone disintegration except an abstract presented in 2001.12 Madbouly et al in 2005 compared slow vs fast shock wave lithotripsy in adults.13 Their study included 156 patients who were prospectively randomized to undergo SWL using a slow (60 pulses per minute) or fast wave rate (120 pulses per minute). They concluded that decreasing the rate of shock waves increases the success rate of SWL at a smaller number of shock waves. In the same year another prospective randomized study by Yilmaz et al compared different shock wave rates in 170 adults with kidney stones.14 The success rate in the group undergoing SWL at slower rates was significantly better, and they concluded that the slower rate has the potential to accomplish better SWL efficacy with fewer shock waves and a lower kV power index, thus minimizing the extent of shock wave induced renal injury. Similar results were also reported in adults by Kato,10 Pace11 and Chacko15 et al. Considering the total number of sessions (number of sessions per patient) as an indicator of success in our study, patients in group 1 displayed excellent results compared to those in group 2 ( p ¼ 0.0112). In vitro and in vivo animal studies have proved that slow rates of shock wave delivery are associated with less tissue damage.16e18 In a study by Delius et al renal parenchymal hemorrhage occurred less with slow rate delivery (1 shock wave per second) than
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with fast rate delivery (100 shock waves per second) in a dog model using the Dornier HM II lithotripter.18 In clinical practice slow shock wave delivery rates decrease tissue damage by reducing the number of shock waves and the number of SWL sessions needed. The possible explanation for the greater success in group 1 is improved cavitation by bubble cluster activity at a slow rate because at a fast rate the number of air bubbles (cavitations) will increase around the stone (not enough time to dissipate and collapse to strike the stone) before arrival of the next wave, leading to attenuation of the coming shock wave front.19 Although the treatment time (mean anesthesia time) was significantly longer in group 1, the greater success rate and the decreased need for secondary procedures outweigh this drawback. Rhee and Palmer in 2006 evaluated ungated SWL in 8 children younger than 18 years and found that it is safe and efficacious, although they did not compare slow and rapid rates of shock wave delivery.20 Palmer in 2009 also evaluated ungated SWL in 14 children younger than 18 years with renal calculi and found it to be safe.21 Although noncontrast computerized tomography has been observed to be more sensitive and specific than KUB and ultrasound for assessing renal stones in adults (Hounsfield units, stone to skin distance, volume of stone by multiple views), concerns remain in children regarding ionizing radiation and the potential for cancer, especially with repeated treatment (latent radiation induced cancer). Children are more susceptible than adults to ionizing radiation exposure, since they have a greater population of dividing cells. To our knowledge our study is the first to demonstrate the effect of slow vs rapid delivery rate SWL for pediatric renal urolithiasis. The strengths of our study include that it is a prospective, randomized, controlled trial (for other confounding factors, including stone size, stone site, operator, number of shock waves received and lithotripter used) that includes only solitary radiopaque stones, and defines success and failure. Limitations of our study include the small number of cases, the fact that stone attenuation could not be assessed before SWL (due to computerized tomography limitations) and the lack of tissue damage assessment by markers such as N-acetyl-B-D-glucosaminidase and urinary lactate dehydrogenase.10
CONCLUSIONS In children with renal stones slow delivery rates of SWL have better stone clearance results than fast delivery rates in terms of treatment success, with fewer secondary procedures. Additional studies are recommended with a larger number of patients.
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SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
REFERENCES 1. Tiselius HG, Ackermann D, Alken P et al: Guidelines on Urolithiasis. Arnhem, The Netherlands: European Association of Urology 2001.
Efficacy, complications and long-term follow-up. Eur Urol 2001; 39: 591.
2. Miller NL and Lingeman JE: Management of kidney stones. BMJ 2007; 334: 468.
9. Weir MJ, Tariq N and Honey RJ: Shockwave frequency affects fragmentation in a kidney stone model. J Endourol 2000; 14: 547.
3. Khairy-Salem H, El Ghoneimy M and El Atrebi M: Semirigid ureteroscopy in management of large proximal ureteral calculi: is there still a role in developing countries? Urology 2011; 77: 1064.
10. Kato Y, Yamaguchi S, Hori J et al: Improvement of stone communication by slow delivery rate of shock waves in extracorporeal lithotripsy. Int J Urol 2006; 13: 1461.
4. Ansari MS: Pediatric urolithiasis: a challenging problem. Indian J Urol 2010; 26: 515.
11. Pace KT, Ghiculete D, Harju M et al: Shock wave lithotripsy at 60 or 120 shocks per minute: a randomized, double-blind trial. J Urol 2005; 174: 595.
5. McAdams S, Kim N, Ravish IR et al: Multiinstitutional analysis demonstrates that stone size is only independent predictor of SWL success in children. J Urol 2009; 181: 585. 6. Newman DM, Coury T, Lingeman JE et al: Extracorporeal shock wave lithotripsy experience in children. J Urol 1986; 136: 238. 7. Muslumanoglu AY, Tefekli A, Sarilar O et al: Extracorporeal shock wave lithotripsy as first line treatment alternative for urinary tract stones in children: a large scale retrospective analysis. J Urol 2003; 170: 2405. 8. Brinkmann OA, Griehl A, Kuwertz-Br€oking E et al: Extracorporeal shock wave lithotripsy in children.
12. Georgiev MI, Panchev P, Yanev K et al: Does frequency of shockwaves influence ESWL success rate of paediatric calculi? Eur Urol 2001; 39: 58. 13. Madbouly K, El-Tiraifi AM and Seida M: Slow versus fast shock wave lithotripsy rate for urolithiasis: a prospective randomized study. J Urol 2005; 173: 127. 14. Yilmaz E, Batislam E, Basar M et al: Optimal frequency in extracorporeal shock wave lithotripsy: prospective randomized study. Urology 2005; 66: 1160.
15. Chacko J, Moore M, Sankey N et al: Does a slower treatment rate impact the efficacy of extracorporeal shock wave lithotripsy for solitary kidney or ureteral stones? J Urol 2006; 175: 1370. 16. Ryan PC, Jones BJ, Kay EW et al: Acute and chronic bioeffects of single and multiple doses of piezoelectric shockwaves (EDAP LT. 01). J Urol 1991; 145: 399. 17. Delius M, Jordan M, Eizenhoefer H et al: Biological effects of shock waves in dogs: administration rate dependence. Ultrasound Med Biol 1988; 14: 689. 18. Delius M, Ueberle F and Eisenmenger W: Extracorporeal shock waves act by shock waveegas bubble interaction. Ultrasound Med Biol 1998; 24: 1055. 19. Pishchalnikov YA, Sapozhnikov OA, Bailey MR et al: Cavitation bubble cluster activity in the breakage of kidney stones by lithotripter shockwaves. J Endourol 2003; 17: 435. 20. Rhee K and Palmer JS: Ungated ESWL in children: an initial series. Urology 2006; 67: 392. 21. Palmer JS: Ungated extracorporeal shock wave lithotripsy: safe and efficacious in pediatric group. Can J Urol 2009; 16: 4924.
EDITORIAL COMMENT The treatment of urinary calculi using shock wave lithotripsy in the pediatric population has evolved during the last 2 decades. SWL has been proved to be safe and efficacious in children with the advent of enhanced shock wave lithotripters and increased experience. Traditionally SWL is performed “gated,” whereby the lithotripsy rate is synchronized to the electrocardiogram. However, within the last decade the use of ungated lithotripsy with a fixed rate has also been shown to be safe and efficacious in children (references 20 and 21 in article).
The authors evaluated the delivery rate of ungated SWL (80 and 120 shock waves per minute) for pediatric renal stones. They demonstrated that a slow delivery rate of SWL has a greater rate of stone clearance, requiring a lower frequency of secondary procedures and resulting in fewer failed procedures. Additional studies involving larger cohorts are recommended with variable delivery rates and energy settings. Jeffrey S. Palmer Pediatric and Adolescent Urology Institute Cleveland, Ohio
REPLY BY AUTHORS We agree with the suggestion that additional studies involving larger cohorts are needed with variable delivery rates and energy (kV) settings, with or without use of the low to high power ramping technique (starting at a low amplitude initially with a gradual
increase). Points of comparison should include successful outcomes in addition to tissue damage effects as assessed by markers such as N-acetyl-B-Dglucosaminidase, urinary lactate dehydrogenase, microalbumin and macroglobulin (reference 10 in article).
Slow vs Rapid Delivery Rate Shock Wave Lithotripsy for Pediatric Renal Urolithiasis: A Prospective Randomized Study Hosni Khairy Salem,* Hesham Fathy, Hanny ElFayoumy, Hussein Aly, Ahmed Ghonium, Mostafa A. Mohsen and Abd El Rahim Hegazy From the Urology Department, Faculty of Medicine, Cairo University, Giza, Egypt
Abbreviations and Acronyms KUB ¼ plain x-ray of kidney, ureters and bladder PCNL ¼ percutaneous nephrolithotomy SWL ¼ shock wave lithotripsy Accepted for publication November 13, 2013. Study received institutional review board approval. * Correspondence: Urology Department, Faculty of Medicine, Cairo University, P. O. Box 247, Giza 12515, Egypt (telephone: 201-006042442, 201-001425799; e-mail: [email protected]).
Purpose: We compared slow vs fast shock wave frequency rates in disintegration of pediatric renal stones less than 20 mm. Materials and Methods: Our study included 60 children with solitary 10 to 20 mm radiopaque renal stones treated with shock wave lithotripsy. Patients were prospectively randomized into 2 groups, ie those undergoing lithotripsy at a rate of 80 shock waves per minute (group 1, 30 patients) and those undergoing lithotripsy at a rate of 120 shock waves per minute (group 2, 30 patients). The 2 groups were compared in terms of treatment success, anesthesia time, secondary procedures and efficiency quotient. Results: Stone clearance rate was significantly higher in group 1 (90%) than in group 2 (73.3%, p ¼ 0.025). A total of 18 patients in group 1 (60%) were rendered stone-free after 1 session, 8 required 2 sessions and 1 needed 3 sessions, while shock wave lithotripsy failed in 3 patients. By comparison, 8 patients (26.6%) in group 2 were rendered stone-free after 1 session, 10 (33.3%) required 2 sessions and 4 (13.3%) needed 3 sessions to become stone-free. Mean general anesthesia time was significantly longer in group 1 (p ¼ 0.041). Postoperatively 2 patients in group 1 and 4 in group 2 suffered low grade fever (Clavien grade II). Significantly more secondary procedures (percutaneous nephrolithotomy, repeat shock wave lithotripsy) were required in group 2 (p ¼ 0.005). The predominant stone analysis was calcium oxalate dihydrate in both groups. Efficiency quotient was 0.5869 and 0.3437 for group 1 and group 2, respectively (p ¼ 0.0247). Conclusions: In children with renal stones slow delivery rates of shock wave lithotripsy have better results regarding stone clearance than fast delivery rates. Key Words: high-energy shock waves, kidney calculi, lithotripsy, pediatrics, urolithiasis
UROLITHIASIS constitutes an important part of our practice.1 The introduction of shock wave lithotripsy during the early 1980s dramatically changed the management of urinary tract stones. During the last 2 decades the development of new lithotripters has changed completely the way in which patients with stones are treated.2,3 Epidemiological studies have revealed an increase in the
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incidence of pediatric stones worldwide.4 It is accepted that pediatric patients have increased clearance rate of stones compared to adults.5 Shock wave lithotripsy was first successfully used in children in 1986,6 and is now considered firstline treatment for the management of pediatric stones of the upper urinary tract.7e9 In adults stone disintegration during SWL has been
0022-5347/14/1915-1370/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.11.028 Vol. 191, 1370-1374, May 2014 Printed in U.S.A.
SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
improved by slowing the rate of delivery. Consequently slow rates of SWL have contributed to better treatment options.10,11 Few studies have focused on the relation of the frequency rate of shock wave delivery to renal stone clearance in adults.10e12 To our knowledge no previous study has been published comparing slow vs fast shock wave frequency rates in pediatric urolithiasis except 1 abstract presented in 2001.12 We compared slow and fast shock wave frequency delivery rates in disintegrating pediatric renal stones smaller than 20 mm and the impact on stone clearance. Terms of comparison included treatment success, anesthesia time, secondary procedures, costs and efficiency quotient.
PATIENTS AND METHODS A total of 60 patients with a mean SD age of 5.56 3.54 years (range 3 to 14) presenting with solitary radiopaque renal stones (10 to 20 mm) between August 2011 and July 2012 were included in the study. Patients were recruited from the outpatient clinic and were prospectively randomized (envelope method) into 2 groups. Group 1 consisted of 30 patients undergoing SWL at 80 shock waves per minute and group 2 included 30 patients undergoing SWL at 120 shock waves per minute. We chose these rates based on previous studies using either rate separately in adults, young adults and children, which had proved safe. Also ungated SWL proved to be safe in children. Exclusion criteria consisted of multiple stones, moderate or severe hydronephrosis, active infection, coagulopathy, stone size less than 10 mm or more than 20 mm, bilateral renal stones, radiolucent stones, anatomical abnormality in the ureter or ureteropelvic junction, cardiac pacemaker and uremia. Preoperative imaging included ultrasound, KUB and/or excretory urography. Maximum longitudinal diameter (length) was used to reflect the size of the stone. The study received institutional review board approval, and parents gave informed consent after proper counseling. All selected patients fulfilling the inclusion criteria were treated with SWL using the Dornier Lithotripter S (Dornier Medical Systems, Kennesaw, Georgia) with the 220 electromagnetic shock wave emitter. Fluoroscopy was used for stone localization. The procedure was done with patients under general anesthesia. Intravenous fluids were administered throughout the procedure. All children underwent lithotripsy using the same device with a gradual incremental energy increase from 14 to 20 kV. We usually start by low amplitude initially and increase it gradually from 14 to 24 kV, except that in children younger than 4 years we increase it to only 18 kV to reduce the possibility of renal tissue injuries. Maximum number of shock waves delivered was 2,500, except if complete fragmentation was evident on fluoroscopy screen before reaching 2,500 shock waves. Patients were kept under observation for 3 hours until fully conscious and urine was relatively clear of blood. On
1371
discharge from the hospital the parents were instructed to maintain adequate fluid intake in their children, in general 1 to 2 cc/kg per hour according to body weight. An analgesic (diclofenac pediatric suppository) was prescribed on discharge home. Parents were also instructed to check for expected hematuria and passage of stone fragments, and to report if the child had a fever or colic. Stone fragments were collected for chemical stone analysis. Patients were reevaluated with KUB and abdominal ultrasound 2 and 4 weeks after the SWL session. Those who had sizable fragments were scheduled for another session 3 weeks later. The maximum number of sessions allowed for our patients was 3. Primary outcome measure was stone-free rate (success rate), while secondary outcome measures included anesthesia time and repeat treatment rate, complications, secondary procedures, cost and efficiency quotient. Stone-free rate was defined as no residual fragments or only 1 clinically insignificant fragment (less than 3 mm, which was nonsymptomatic, noninfectious and nonobstructive) on KUB and ultrasound. Unsuccessful SWL was defined as lack of evidence of disintegration or fragmentation on KUB and ultrasound after 3 SWL sessions. Data were statistically described in terms of mean SD and range, or frequency (number of cases) and percentages when appropriate. Comparison of numerical variables between the 2 groups was done using the Student t-test for independent samples. For comparing categorical data chisquare testing was performed, with the Fisher exact test used when the expected frequency was less than 5. All p values less than 0.05 were considered statistically significant. All statistical calculations were done using SPSSÒ, version 15 for WindowsÒ.
RESULTS Table 1 shows demographic data and outcomes for the 2 groups. The groups were comparable in terms of age, male-to-female ratio, stone size, stone site and total number of shock waves administered. The success rate in group 1 was 90%, with success in 27 patients and failure in 3, compared to a 73.3% success rate in group 2, with success in 22 patients and failure in 8. A total of 18 patients in group 1 were rendered stone-free after 1 session, 8 needed 2 sessions and 1 needed 3 sessions, while SWL failed in 3 patients. By comparison, 8 patients in group 2 required 1 session, 10 required 2 and 4 needed 3 sessions to become stone-free, with 8 failing SWL. Mean time of general anesthesia was significantly longer in group 1 (table 1). Postoperatively 2 patients in group 1 and 4 in group 2 suffered low grade fever (Clavien grade II). Subcapsular hematoma or significant hematuria was not reported in either group. No arrhythmia was detected during SWL sessions. The 11 cases that failed SWL (3 in group 1 and 8 in group 2) subsequently were managed by PCNL. Number of repeat treatments and secondary procedures (PCNL or
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SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
Table 1. Demographic data and treatment outcomes Group 1 No. gender (%): Male Female Mean SD body mass index Mean SD yrs age (range) No. laterality (%): Rt Lt Mean SD stone size (mm) No. site: Pelvis Middle calyx Lower pole Mean SD shock waves Mean anesthesia time (mins) No. success (%): After 1 session After 2 sessions After 3 sessions Total No. secondary procedures: Repeat SWL PCNL No. predominant stone analysis (%): Calcium oxalate monohydrate Calcium oxalate dihydrate Calcium phosphate Mixed calcium oxalate þ calcium phosphate Efficiency quotient Requirement for 30 pts to be stone-free No. sessions/No. pts (mean SD sessions)
Group 2
p Value 0.695
20 10 22.7 5.35 12 18 15.02
(33.3) (66.7) 2.5 3.67 (3e14) (40) (60) 2.47
15 6 9 2,300 150 37.02 18 8 1 27
18 12 23.4 6.67 13 17 13.85
(60.0) (40.0) 3.1 2.94 (3e13)
0.179 0.085 0.546
(43.7) (56.7) 3.42
0.563 0.836
18 7 5 2,450 110 25.43 (60.0) (26.6) (3.3) (90)
8 10 4 22
(10%)
34 8
0.256 0.041 0.025 (26.6) (33.3) (13.3) (73.3) 0.005
16 3
(26.7%) 0.457
5 (16.7) 20 (66.6) 2 (6.6) 3 (9.9) 0.5869 46 SWL sessions (30 primary þ 16 repeat), 3 PCNLs 46/30 (1.53 0.35)
repeat SWL) were significantly greater in group 2 (16 SWL sessions and 3 PCNLs in group 1 vs 34 SWL sessions and 8 PCNLs in group 2). The predominant stone analysis was calcium oxalate dihydrate in both groups (66% in group 1 and 60% in group 2). Efficiency quotient was 0.5869 and 0.3437 for group 1 and group 2, respectively (p ¼ 0.0247), which is statistically significant. Mean SD SWL sessions per patient were significantly greater in group 2 than in group 1 (table 1). Three patients in group 1 failed SWL. Stone sizes in these patients were 1.5, 1.8 and 2.0 cm. All stones were in the pelvis. Two stones consisted of calcium oxalate monohydrate, while 1 was mixed (table 2). Eight patients in group 2 failed SWL. Stone sizes were more than 1.5 cm in 7 cases (range 1.0 to 2). One stone was in the lower pole, 3 were in the middle calyx and 4 were in the pelvis. Five stones were calcium oxalate monohydrate and 3 were calcium oxalate dihydrate (table 2). Regarding first session success for smaller stones (10 to 15 mm), no significant difference was noted between the groups (table 3). For larger stones (15 to 20 mm) the low frequency group had significantly better results. Regarding the first session success in the low frequency group, the results were better for large stones than for small stones. In the high frequency
6 (19.6) 18 (60.5) 4 (13.3) 2 (6.6) 0.3437 64 SWL sessions (30 primary þ 34 repeat), 8 PCNLs 64/30 (2.1 0.25)
0.0247 e 0.0112
group no difference in results was noted between small stones and large stones (table 3).
DISCUSSION Our study included 60 patients presenting with renal stones treated with SWL divided randomly into 2 groups. Group 1 consisted of 30 patients who Table 2. Analysis of treatment failures after 3 sessions
Pt age (yrs) No. gender: Male Female Body mass index No. laterality: Rt Lt No. stone size (mm): 10e15 15e20 No. site/total No.: Pelvis Middle calyx Lower calyx No. sessions No. shock waves No. stone analysis: Calcium oxalate monohydrate Calcium oxalate dihydrate Calcium phosphate Mixed
Group 1
Group 2
5e9
3e10
1 2 12.0e14.0
4 4 18.3e28.5
3 0
3 5
0 3
1 7
3/15 0/6 0/9 3 2,500
4/18 3/7 1/5 3 2,500
2 0 0 1
5 3 0 0
SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
Table 3. First session success according to stone size and site
No. site/total No.: Pelvis Middle calyx Lower calyx No. size(mm)/total No. 10e15 15e20 No. stone analysis: Calcium oxalate monohydrate Calcium oxalate dihydrate Calcium phosphate Mixed
Group 1
Group 2
10/15 5/6 3/9
6/18 1/7 1/5
6/14 12/16
4/16 4/14
2 14 2 0
0 6 0 2
p Value 0.557
0.351 0.0451 0.0244
underwent SWL using 80 shock waves per minute, and group 2 included 30 patients who underwent SWL using 120 shock waves per minute. In group 1 success was observed in 27 patients (90%) and failure occurred in 3, while in group 2 success was observed in 22 patients (73.3%) and failure occurred in 8. The success rate after the first session was significantly higher in group 1 than in group 2 (60.0% vs 26.6%). In the remaining patients the success rate after a second session was 26.6% in group 1 and 33.3% in group 2. For the remainder the success rate after a third session was 3.3% in group 1 and 13.3% in group 2. We found no study in the literature comparing the effect of SWL delivery rates (slow vs fast) in pediatric stone disintegration except an abstract presented in 2001.12 Madbouly et al in 2005 compared slow vs fast shock wave lithotripsy in adults.13 Their study included 156 patients who were prospectively randomized to undergo SWL using a slow (60 pulses per minute) or fast wave rate (120 pulses per minute). They concluded that decreasing the rate of shock waves increases the success rate of SWL at a smaller number of shock waves. In the same year another prospective randomized study by Yilmaz et al compared different shock wave rates in 170 adults with kidney stones.14 The success rate in the group undergoing SWL at slower rates was significantly better, and they concluded that the slower rate has the potential to accomplish better SWL efficacy with fewer shock waves and a lower kV power index, thus minimizing the extent of shock wave induced renal injury. Similar results were also reported in adults by Kato,10 Pace11 and Chacko15 et al. Considering the total number of sessions (number of sessions per patient) as an indicator of success in our study, patients in group 1 displayed excellent results compared to those in group 2 ( p ¼ 0.0112). In vitro and in vivo animal studies have proved that slow rates of shock wave delivery are associated with less tissue damage.16e18 In a study by Delius et al renal parenchymal hemorrhage occurred less with slow rate delivery (1 shock wave per second) than
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with fast rate delivery (100 shock waves per second) in a dog model using the Dornier HM II lithotripter.18 In clinical practice slow shock wave delivery rates decrease tissue damage by reducing the number of shock waves and the number of SWL sessions needed. The possible explanation for the greater success in group 1 is improved cavitation by bubble cluster activity at a slow rate because at a fast rate the number of air bubbles (cavitations) will increase around the stone (not enough time to dissipate and collapse to strike the stone) before arrival of the next wave, leading to attenuation of the coming shock wave front.19 Although the treatment time (mean anesthesia time) was significantly longer in group 1, the greater success rate and the decreased need for secondary procedures outweigh this drawback. Rhee and Palmer in 2006 evaluated ungated SWL in 8 children younger than 18 years and found that it is safe and efficacious, although they did not compare slow and rapid rates of shock wave delivery.20 Palmer in 2009 also evaluated ungated SWL in 14 children younger than 18 years with renal calculi and found it to be safe.21 Although noncontrast computerized tomography has been observed to be more sensitive and specific than KUB and ultrasound for assessing renal stones in adults (Hounsfield units, stone to skin distance, volume of stone by multiple views), concerns remain in children regarding ionizing radiation and the potential for cancer, especially with repeated treatment (latent radiation induced cancer). Children are more susceptible than adults to ionizing radiation exposure, since they have a greater population of dividing cells. To our knowledge our study is the first to demonstrate the effect of slow vs rapid delivery rate SWL for pediatric renal urolithiasis. The strengths of our study include that it is a prospective, randomized, controlled trial (for other confounding factors, including stone size, stone site, operator, number of shock waves received and lithotripter used) that includes only solitary radiopaque stones, and defines success and failure. Limitations of our study include the small number of cases, the fact that stone attenuation could not be assessed before SWL (due to computerized tomography limitations) and the lack of tissue damage assessment by markers such as N-acetyl-B-D-glucosaminidase and urinary lactate dehydrogenase.10
CONCLUSIONS In children with renal stones slow delivery rates of SWL have better stone clearance results than fast delivery rates in terms of treatment success, with fewer secondary procedures. Additional studies are recommended with a larger number of patients.
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SHOCK WAVE LITHOTRIPSY DELIVERY RATE FOR PEDIATRIC KIDNEY STONES
REFERENCES 1. Tiselius HG, Ackermann D, Alken P et al: Guidelines on Urolithiasis. Arnhem, The Netherlands: European Association of Urology 2001.
Efficacy, complications and long-term follow-up. Eur Urol 2001; 39: 591.
2. Miller NL and Lingeman JE: Management of kidney stones. BMJ 2007; 334: 468.
9. Weir MJ, Tariq N and Honey RJ: Shockwave frequency affects fragmentation in a kidney stone model. J Endourol 2000; 14: 547.
3. Khairy-Salem H, El Ghoneimy M and El Atrebi M: Semirigid ureteroscopy in management of large proximal ureteral calculi: is there still a role in developing countries? Urology 2011; 77: 1064.
10. Kato Y, Yamaguchi S, Hori J et al: Improvement of stone communication by slow delivery rate of shock waves in extracorporeal lithotripsy. Int J Urol 2006; 13: 1461.
4. Ansari MS: Pediatric urolithiasis: a challenging problem. Indian J Urol 2010; 26: 515.
11. Pace KT, Ghiculete D, Harju M et al: Shock wave lithotripsy at 60 or 120 shocks per minute: a randomized, double-blind trial. J Urol 2005; 174: 595.
5. McAdams S, Kim N, Ravish IR et al: Multiinstitutional analysis demonstrates that stone size is only independent predictor of SWL success in children. J Urol 2009; 181: 585. 6. Newman DM, Coury T, Lingeman JE et al: Extracorporeal shock wave lithotripsy experience in children. J Urol 1986; 136: 238. 7. Muslumanoglu AY, Tefekli A, Sarilar O et al: Extracorporeal shock wave lithotripsy as first line treatment alternative for urinary tract stones in children: a large scale retrospective analysis. J Urol 2003; 170: 2405. 8. Brinkmann OA, Griehl A, Kuwertz-Br€oking E et al: Extracorporeal shock wave lithotripsy in children.
12. Georgiev MI, Panchev P, Yanev K et al: Does frequency of shockwaves influence ESWL success rate of paediatric calculi? Eur Urol 2001; 39: 58. 13. Madbouly K, El-Tiraifi AM and Seida M: Slow versus fast shock wave lithotripsy rate for urolithiasis: a prospective randomized study. J Urol 2005; 173: 127. 14. Yilmaz E, Batislam E, Basar M et al: Optimal frequency in extracorporeal shock wave lithotripsy: prospective randomized study. Urology 2005; 66: 1160.
15. Chacko J, Moore M, Sankey N et al: Does a slower treatment rate impact the efficacy of extracorporeal shock wave lithotripsy for solitary kidney or ureteral stones? J Urol 2006; 175: 1370. 16. Ryan PC, Jones BJ, Kay EW et al: Acute and chronic bioeffects of single and multiple doses of piezoelectric shockwaves (EDAP LT. 01). J Urol 1991; 145: 399. 17. Delius M, Jordan M, Eizenhoefer H et al: Biological effects of shock waves in dogs: administration rate dependence. Ultrasound Med Biol 1988; 14: 689. 18. Delius M, Ueberle F and Eisenmenger W: Extracorporeal shock waves act by shock waveegas bubble interaction. Ultrasound Med Biol 1998; 24: 1055. 19. Pishchalnikov YA, Sapozhnikov OA, Bailey MR et al: Cavitation bubble cluster activity in the breakage of kidney stones by lithotripter shockwaves. J Endourol 2003; 17: 435. 20. Rhee K and Palmer JS: Ungated ESWL in children: an initial series. Urology 2006; 67: 392. 21. Palmer JS: Ungated extracorporeal shock wave lithotripsy: safe and efficacious in pediatric group. Can J Urol 2009; 16: 4924.
EDITORIAL COMMENT The treatment of urinary calculi using shock wave lithotripsy in the pediatric population has evolved during the last 2 decades. SWL has been proved to be safe and efficacious in children with the advent of enhanced shock wave lithotripters and increased experience. Traditionally SWL is performed “gated,” whereby the lithotripsy rate is synchronized to the electrocardiogram. However, within the last decade the use of ungated lithotripsy with a fixed rate has also been shown to be safe and efficacious in children (references 20 and 21 in article).
The authors evaluated the delivery rate of ungated SWL (80 and 120 shock waves per minute) for pediatric renal stones. They demonstrated that a slow delivery rate of SWL has a greater rate of stone clearance, requiring a lower frequency of secondary procedures and resulting in fewer failed procedures. Additional studies involving larger cohorts are recommended with variable delivery rates and energy settings. Jeffrey S. Palmer Pediatric and Adolescent Urology Institute Cleveland, Ohio
REPLY BY AUTHORS We agree with the suggestion that additional studies involving larger cohorts are needed with variable delivery rates and energy (kV) settings, with or without use of the low to high power ramping technique (starting at a low amplitude initially with a gradual
increase). Points of comparison should include successful outcomes in addition to tissue damage effects as assessed by markers such as N-acetyl-B-Dglucosaminidase, urinary lactate dehydrogenase, microalbumin and macroglobulin (reference 10 in article).
