Rapid Extracorporeal Shock Wave Lithotripsy for Proximal Ureteral Calculi in Colic versus Noncolic Patients

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1 european urology 52 (2007) available at journal homepage: Stone Disease Rapid Extracorporeal Shock Wave Lithotripsy for Proximal Ureteral Calculi in Colic versus Noncolic Patients Christian Seitz a, *, Enis Tanovic a, Zeljko Kikic a, Mazda Memarsadeghi b, Harun Fajkovic c a Medical University of Vienna, Vienna, Austria b Department of Radiology, Medical University of Vienna, Vienna, Austria c Military Hospital Vienna, Austria Article info Article history: Accepted February 5, 2007 Published online ahead of print on February 12, 2007 Keywords: Colic ESWL Noncolic Proximal ureter Stone clearance Abstract Objectives: In delayed extracorporeal shock wave lithotripsy (ESWL) treatment, increasing stone impaction is associated with delayed stone clearance. Whether colic patients treated by rapid ESWL have the same time to stone clearance as noncolic patients, which supports the thesis that stones in both groups are nonimpacted, has not been investigated yet, and was the objective of this study. Methods: A total of 82 patients were prospectively enrolled and treated with piezoelectric ESWL for a solitary proximal ureteral stone. Of these, 56 patients experienced at least one colic episode compared with 26 noncolic patients. Hydronephrosis has been assessed with the use of ultrasound and intravenous urography (IVU). Time to stone clearance after the first ESWL and stone-free rates after a follow-up period of 3 mo were recorded. Results: In colic and noncolic patients, mean stone size was 7.8 mm ( p = 0.7). Ultrasound-detected hydronephrosis was present in 88% versus 39% ( p < ), whereas IVU-detected hydronephrosis was present in 60% versus 7.7% ( p = ). Mean number of impulses applied was versus ( p = 0.1). Mean time to stone clearance was d versus d ( p = 0.1). Colic and noncolic patients were considered as treatment success in 83% and 81% after 3 mo of follow-up ( p = 0.9). Conclusions: Treatment outcome and time to stone clearance after rapid ESWL in colic patients compared with noncolic patients is comparable and independent of concomitant hydronephrosis. This finding suggests an absence of significant impaction in proximal ureteral stones treated within 24 h after a first colic episode, enforcing the concept of performing rapid ESWL in patients harbouring proximal ureteral stones. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Medical University of Vienna, Währinger Gürtel 18 20, 1090 Vienna, Austria. Tel. +43 (1) ; Fax: +43 (1) address: drseitz@gmx.at (C. Seitz) /$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 1224 european urology 52 (2007) Introduction Extracorporeal shock wave lithotripsy (ESWL) is currently recommended as first-line therapy for proximal ureteral stones of any size [1]. The literature comprises numerous reports with variable success rates. This lack of consistency of success rates is related to stone size, degree of impaction, extent to which shock wave sessions are repeated, and the type of lithotripter used. The main purpose of treatment is to achieve a stone-free status as soon and as safely as possible, reducing treatment failures necessitating auxiliary measures. The influence of symptoms and obstruction on time to stone clearance remain controversial. As recently shown, colic patients harbouring proximal ureteral stones profit from rapid ESWL (24 h) in terms of a decreased time to stone clearance and an increased treatment success [2 4]. One explanation is that symptomatic ureteral stones treated with rapid ESWL are unlikely to be impacted because they did not have enough time to develop a surrounding edema. This study investigated rapid ESWL in proximal ureteral stones in colic patients compared with noncolic patients on the basis of the assumption that stones in both groups are not impacted yet and, therefore, have a favourable time to stone clearance compared with colic patients treated with delayed ESWL. 2. Material and methods A total of 82 patients with a solitary proximal ureteral stone and either at least one episode of acute renal colic and no previous active treatment (n = 56), or no colic episode (n = 26) were prospectively, nonrandomly enrolled in the study at a single institution between March 2003 and May Rapid ESWL in colic patients was performed within 24 h after their first colic episode. Noncolic patients were scheduled as soon as possible, usually within a 5-d period after presentation. Stones were detected by either noncontrast computerised tomography (NCCT) when symptomatic or by intravenous urography (IVU) in the asymptomatic interval. Noncolic patients harbouring proximal ureteral stones never experienced an episode of colic pain. They were detected incidentally in radiologic or ultrasound investigations of concomitant diseases or haematuria, or after routine follow-up of prior urolithiasis. Patients with ureteric strictures or clotting disorders were excluded. Laboratory investigations included urinalysis, urinary culture, coagulation profile, and serum creatinine determination. All patients were afebrile, but urinary cultures were positive in seven individuals (9%) who received appropriate antimicrobial drugs prior to ESWL. Stone size was measured by using urinary tract plain X-ray (KUB). Stents were not routinely placed because they do not decrease the incidence of steinstrasse in moderate-sized stones [5]. The presence and degree of a hydronephrosis were assessed with the use of ultrasound at initial presentation of the patient. The degree of hydronephrosis was defined as mild if the renal pelvis only was dilated, and as moderate if the renal pelvis and calices were dilated. Patients with severe hydronephrosis and rarefaction of the renal parenchyma were not observed. The presence of a hydronephrosis was additionally assessed by performing an IVU (Table 1). Images were routinely taken 7, 15, 25, and 30 min (postmicturition) after contrast application. When necessary, further images for up to 5 h were taken. The time for the contrast material to advance beyond the ureteral stone was recorded prior to ESWL treatment. Results were stratified into three groups: group 1: excretion within 7 min; group 2: between 7 and 30 min; and group 3: after 30 min for up to 5 h. Initial ESWL treatment was performed as an inpatient procedure with the newest Piezolith 3000 (Richard Wolf, Knittlingen, Germany) with dual ultrasound/fluoroscopic stone detection. Opacification of the excretory route was never required. All stones were located in the proximal ureter, and were radiographically defined as between the ureteropelvic junction and the pelvic brim. The Table 1 Differences between colic patients undergoing rapid ESWL and noncolic patients N = 82 Age (yr) Stone size (mm) Creatinine (mg/dl) IVU Hydronephrosis Sonography Colic % 88% Noncolic % 39% p value < * <0.002 * IVU excretion at 7 min (%) IVU excretion at 30 min (%) Impulses (10 3 ) Therapy success z (%) Therapy success after ESWL (d) Colic (median: 5.5) Noncolic (median: 3) p value 0.08 * * 0.1 IVU = intravenous urography; ESWL = extracorporeal shock wave lithotripsy. Wilcoxon test. * Fisher exact test. z After 3 mo.

3 european urology 52 (2007) urologists performing ESWL were not aware of the study objective. Routine pain control, when necessary during ESWL, was intravenous metamizol 2.5 g on demand. Stents were not inserted prior to ESWL. The time between the first onset of colic pain and ESWL treatment in colic patients, and the time between the first ESWL session and stone clearance in colic and noncolic patients were recorded. Patients in whom ESWL failed to completely disintegrate the stone during the first treatment underwent retreatment the next day. Those in whom ESWL had no impact on the stone at all during the first session, as evidenced by KUB, underwent ureterorenoscopy (URS) or percutaneous nephrolitholapaxy (PNL). Stone-free status was established by KUB and IVU as well as by NCCT in cases for which residual fragments could not be excluded. Therapy-refractory colic pain or persistence of fragments >3 mm after repeated ESWL sessions necessitating auxiliary procedures was considered indicative of treatment failure. Patients with stones 3 mm in diameter without the need for auxiliary measures within a 3-mo follow-up period were defined as a treatment success. Patients were reviewed 1 d after each ESWL session with KUB and renal ultrasound to assess stone fragmentation and hydronephrosis. Incomplete fragmentation after a maximum of four sessions was considered an ESWL failure. Follow-up continued for a maximum of 3 mo using KUB and renal ultrasound every 2 wk or after each stone passage until complete clearance was achieved. Stone analysis to determine the crystalline structure was carried out with the use of X-ray diffraction. Primary and secondary end points were time to stone clearance and failure rates after ESWL treatment in colic and noncolic patients. JMP version software (SAS Institute, Inc, Cary, NC, USA) was used for statistical analysis. Wilcoxon, Pearson correlations, and Fisher exact tests were used for comparison between continuous variables and linear regression. 3. Results Mean patient age in colic patients was yr (range: 21 81) and yr in noncolic patients (range: 29 81; p = 0.7). The maximum stone diameter in colic compared with noncolic patients was (range: 4 15 mm) versus mm (range: 4 18 mm).there were no significant differences in the gender distribution between both groups ( p = 0.06). Of 82 patients, 56 experienced at least one colic episode prior to admission and underwent rapid ESWL. Mean time to ESWL after a first colic episode was h (range: ). Of colic patients 52% (n = 29) required one session only, 25% (n = 14) a second, 20% (n = 11) a third, and 4% (n = 2) a fourth session. In the noncolic group 62% (n = 16) of patients required one session only, 19% (n = 5) a second, and 19% (n = 5) a third session for complete stone fragmentation ( p = 0.4). The mean number of impulses applied to achieve treatment success per patient in both groups was insignificantly higher in colic patients ( vs ; p = 0.1). No difference in impulse intensity was noted ( vs ; p > 0.9). Colic patients in 74% ( p = 40) were stone-free and 9% (n = 5) harboured residual fragments 3 mm after 3-mo follow-up; hence, 83% (n = 45) were considered a treatment success. Of the 26 noncolic patients, 73% (n = 19) were stone-free, and 7.7% (n = 2) harboured residual fragments 3 mm, with 81% (n = 21) considered a treatment success. At initial presentation of the patient, hydronephrosis detected by ultrasound was observed in 88% (n = 49) of colic patients. In noncolic patients hydronephrosis was present in 39% (n = 10). Although differences in the presence and degree of hydronephrosis in both groups were significant ( p = 0.002), neither the presence nor the degree of hydronephrosis had an impact on the time to stone clearance or on treatment success. An IVU was performed prior to ESWL treatment in a colic-free interval. IVU detected hydronephrosis in colic and noncolic patients was present in 59% (n = 33) versus 7.7% ( p < ). Again, the proportion of hydronephrosis was significantly greater in colic patients but again had no significant influence on time to stone clearance or on treatment success. In colic versus noncolic patients, immediate excretion of contrast material beyond the stone within 7 min was found in 48% versus 82%, within 30 min in 72% versus 88%, and in 100% up to 5 hours thereafter. The overall mean time to stone clearance in colic versus noncolic patients was d (median: 5.5 d) versus d (median: 3 d) ( p = 0.1) (Table 1). Serum creatinine levels between colic and noncolic patients were not significantly different. ( vs mg/dl; p = 0.1). A steinstrasse with the need for an auxiliary procedure was observed in one patient in each group, and 93% of stones were radioopaque. There was no difference in radioopacity or the proportion of calcium oxalate monohydrate/dehydrate. Insufficient material for analysis was collected in nine patients. 4. Discussion Spontaneous stone passage can be expected in up to 80% in patients with stones <4 mm in diameter. For stones with a diameter >5 mm, the chance of spontaneous passage declines [6 9]. A variety of influential factors for spontaneous passage of ureteral stones consisting of hydrostatic pressure proximal to the calculus, edema, inflammation, and spasm of the ureter at the site of the stone are described [10,11]. Relaxation of the ureter appears to

4 1226 european urology 52 (2007) facilitate ueteral stone passage in the region of the stone [10]. With respect to the potential facilitative effect of ureteral relaxation on stone passage, a-blocker and b-agonists have been shown to relax the ureteral wall at the level of an artificial stone, permitting fluid flow beyond the stone [12]. Recently a-blockade has indeed been shown to be beneficial in reducing the time of stone expulsion and number of colic events, and in increasing the number of stone passages, either without interventional therapy or after ESWL treatment [13 16]. It has been assumed that ureteral edema formation over time caused by a symptomatic impacted ureteral calculus impairs stone clearance after ESWL [17]. This assumption is supported by the fact that rapid ESWL after a first onset of colic pain led to an accelerated stone clearance in proximal ureteral stones [1,2] and that a gradual increase of the time after a first colic episode until ESWL treatment significantly correlated with a delayed stone clearance [4]. Our finding of a nonsignificant difference in time to stone clearance between colic patients undergoing rapid ESWL and noncolic patients is compatible with the assumption that a significant ureteral edema formation does not occur within 24 h after a first colic episode. Nevertheless, within 1 d, the presence of colic pain seemed to be associated with hydronephrosis and a slightly delayed excretion of contrast material, possibly caused by a beginning ureteral edema; hence, ureteral stones in colic patients treated within 24 h seemed not to be impacted yet. This observation is supported by the finding that colic patients undergoing delayed ESWL demonstrated a significant prolonged time to IVU contrast excretion and time to stone clearance (unpublished data). Clinically significant changes occur only after 24 h, with gradual impaction impairing stone clearance. The correlation is explained by the development of mucosal edema within days, with impacted stones in the ureter [17]. Histologic studies of the mucosa in the stone bed have indeed revealed a hyperplastic appearance with increased mitotic activity [18]. Therefore, it is beneficial for colic patients to undergo ESWL as soon as possible before such morphologic changes occur. Cummings et al [19] reported identification of the pretreatment duration of symptoms in ureteral stones as being the most important factor for prediction of treatment outcome and spontaneous stone passage in an artificial neural network; stone position also ranked highly, but the relative weight assigned by the artificial neural network was 10-fold less than that of symptom duration. It could be anticipated that time to stone clearance is hampered by concomitant impaired renal function. Srivastava et al [20] recently assessed the efficiency of ESWL for stones in renal units with impaired function as determined by split glomerular filtration rate, IVU, and a renal dynamic scan. Clearance rates for ureteral stones were not influenced by the impairment of renal function. Accordingly, we did not find a decline in treatment success with rising creatinine levels. Ultrasound-detected hydronephrosis influenced neither the time to stone clearance nor the treatment outcome; this finding has been reported in a recent study including colic and noncolic patients and in other studies showing no correlation of ureteral stone-induced hydronephrosis with treatment success after ESWL [21 23]. We confirmed these results by assessing IVU-detected nonhydronephrotic and hydronephrotic colic patients, which demonstrated insignificant differences in time to stone clearance ( p = 0.7). The number of impulses applied was not significantly different in both groups. Our finding was in accordance with a recent finding that demonstrated a significant higher number of impulses applied in colic patients treated after 24 h compared with colic patients treated with rapid ESWL [4]. This difference might well be explained by an increasing ureteral edema, and a subsequent lack of an expansion chamber and liquid interface, which reduced initial ESWL fragmentation rates. No evidence so far supports a beneficial effect of rapid ESWL for noncolic patients. 5. Conclusions Treatment outcome and time to stone clearance after rapid ESWL in colic patients are comparable to those of noncolic patients and are independent of concomitant hydronephrosis. This finding suggests an absence of significant impaction in proximal ureteral stones treated within 24 h after a first colic episode, thus enforcing the concept of rapid ESWL treatment in patients harbouring symptomatic proximal ureteral stones. Conflicts of interest The authors have nothing to disclose. References [1] Tiselius HG, Ackermann D, Alken P, et al. EAU Guidelines on urolithiasis. Nijmegen. The Netherlands: European Association of Urology; p. 51.

5 european urology 52 (2007) [2] Tombal B, Mawlawi H, Feyaerts A, et al. Prospective randomized evaluation of emergency extracorporeal shock wave lithotripsy (ESWL) on the short-time outcome of symptomatic ureteral stones. Eur Urol 2005;47: Corrigendum. Eur Urol 2005;48:876. [3] Kravchick S, Bunkin I, Stepnov E, et al. Emergency extracorporeal shock wave lithotripsy for acute renal colic caused by upper urinary-tract stones. J Endourol 2005;19: 1 4. [4] Seitz C, Fajkovic H, Remzi M, et al. Rapid extracorporeal shock wave lithotripsy treatment after a first colic episode correlates with accelerated ureteral stone clearance. Eur Urol 2006;49: [5] Skolarikos A, Alivizatos G, De la Rosette J. Extracorporeal shock wave lithotripsy 25 years later: complications and their prevention. Eur Urol 2006;50: [6] Marberger M, Hofbauer J, Turk C, et al. Management of ureteric stones. Eur Urol 1994;25: [7] Miller OF, Kane CJ. Time to stone passage for observed ureteral calculi: a guide for patient education. J Urol 1999;162: [8] Morse RM, Resnick MI. Ureteral calculi: natural history and treatment in an era of advanced technology. J Urol 1991;145: [9] Ibrahim AI, Shelty SD, Awad RM, et al. Prognostic factors in the conservative treatment of ureteric stones. Br J Urol 1991;67: [10] Sivula A, Lehtonen T. Spontaneous passage of artificial concretions applied in the rabbit ureter. Scand J Urol Nephrol 1967;1: [11] Holmlund D, Hassler O. A method of studying the ureteral reaction to artificial concrements. Acta Chir Scand 1965;130: [12] Peters HJ, Eckstein W. Possible pharmacological means of treating renal colic. Urol Res 1975;3:55 9. [13] Gravina GL, Costa AM, Ronchi P, et al. Tamsulosin treatment increases clinical success rate of single extracorporeal shock wave lithotripsy of renal stones. Urol 2005;66:24 8. [14] Resim S, Ekerbicer HC, Ciftci A. Role of tamsulosin in treatment of patients with steinstrasse developing after extracorporeal shock wave lithotripsy. Urology 2005;66: [15] Porpiglia F, Vaccino D, Billia M, et al. Corticosteroids and tamsulosin in the medical expulsive therapy for symptomatic distal ureter stones: single drug or association? Eur Urol 2006;50: [16] De Sio M, Autorino R, Di Lorenzo G, et al. Medical expulsive treatment of distal-ureteral stones using tamsulosin: a single center experience. J Endourol 2006;20: [17] Mueller SC, Wilbert D, Thueroff JW. Extracorporeal shock wave lithotripsy of ureteral stones: clinical experience and experimental findings. J Urol 1986;135: [18] Kim HL, Labay PC, Boyarsky S, et al. An experimental model of ureteral colic. J Urol 1970;104: [19] Cummings JM, Boullier JA, Izenberg SD, et al. Prediction of spontaneous ureteral calculous passage by an artificial neural network. J Urol 2000;164: [20] Srivastava A, Sinha T, Karan SC, et al. Assessing the efficiency of extracorporeal shockwave lithotripsy for stones in renal units with impaired function: a prospective controlled study. Urol Res 2006;34: [21] Cass AS. In situ extracorporeal shock wave lithotripsy for obstructing ureteral stones with acute renal colic. J Urol 1992;148: [22] Seitz C, Fajkovic H, Waldert M, et al. Extracorporeal shock wave lithotripsy in the treatment of proximal ureteral stones: does the presence and degree of hydronephrosis affect success? Eur Urol 2006;49: [23] Demirbas M, Kose AC, Samli M, et al. Extracorporeal shock wave lithotripsy for solitary distal ureteral stones: does the degree of ureteral obstruction affect success? J Endourol 2004;18: Editorial Comment on: Rapid Extracorporeal Shock Wave Lithotripsy for Proximal Ureteral Calculi in Colic versus Noncolic Patients Roberto Miano Division of Urology, Policlinico Tor Vergata, University of Tor Vergata, Rome, Italy mianor@virgilio.it Rapid extracorporeal shock wave lithotripsy (ESWL) is an emerging management strategy for patients with proximal ureteral calculi, based on the hypothesis that stone impaction could influence treatment outcome. Impaction is defined as adhesion of the stone to the ureteric wall because of fibrin bounds. Although we can assume that stone impaction takes time to develop and delayed ESWL can give enough time for the stone to adhere to the ureteric wall, we cannot exclude that stones are already impacted when patients present to the emergency room. From a clinical standpoint, stone impaction is frequently associated with upper urinary tract dilatation. Therefore, patients with no hydronephrosis can be considered as patients with no stone impaction. Symptoms related to ureteral stones are not necessarily associated with dilation because renal colic may develop in the absence of a demonstrable hydronephrosis. Patients with ureteral stones, no upper urinary tract dilatation, and negative history for stone-related pain are rare, but they can be considered as patients with no stone impaction and constitute a good model for nonimpacted ureteral stones. Analysis of previously published peer-reviewed literature suggests that rapid ESWL offers good clinical outcome and provides preliminary data showing accelerated stone clearance compared to delayed treatment [1 4]. Looking at the patient

6 1228 european urology 52 (2007) population of the cited manuscripts, enrolled patients were symptomatic so that the absence of stone impaction could not be ruled out. In the current study, the authors should be congratulated for providing additional information on this subject and for reporting data on patients with the lowest possible risk of stone impaction [5]. In conclusion, the present manuscript provides new evidence for early ESWL treatment of proximal ureteric stones based on the hypothesis that extracorporeal treatment of nonimpacted stones offers the best chance for rapid stone clearance. The question remains open as to the definition of early versus delayed ESWL. References [1] Tligui M, El Khadime MR, Tchala K, et al. Emergency extracorporeal shock wave lithotripsy (ESWL) for obstructing ureteral stones. Eur Urol 2003;43: [2] Tombal B, Mawlawi H, Feyaerts A, Wese FX, Opsomer R, Van Cangh PJ. Prospective randomized evaluation of emergency extracorporeal shock wave lithotripsy (ESWL) on the short-time outcome of symptomatic ureteral stones. Eur Urol 2005;47: Corrigendum. Eur Urol 2005;48:876. [3] Kravchick S, Bunkin I, Stepnov E, Peled R, Agulansky L, Cytron S. Emergency extracorporeal shock wave lithotripsy (ESWL) for acute renal colic caused by upper urinary-tract stones. J Endourol 2005;19:1 4. [4] Seitz C, Fajcovic H, Remzi M, et al. Rapid extracorporeal shock wave lithotripsy treatment after a first colic episode correlates with accelerated ureteral stone clearance. Eur Urol 2006;49: [5] Seitz C, Tanovic E, Kikic Z, Memarsadeghi M, Fajcovic H. Rapid extracorporeal shock wave lithotripsy for proximal ureteral calculi in colic versus non-colic patients. Eur Urol 2007;52: DOI: /j.eururo DOI of original article: /j.eururo