61 Thomas Tailly1 & Hassan Razvi2 1 Division of Urology, University Hospital Ghent, Ghent, Belgium 2 Division of Urology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada Over the past decade, the number of patients with upper urinary tract calculi undergoing shock‐wave lithotripsy (SWL) has decreased across the globe [1, 2]. This trend is a reflection of a number of factors including improvements and widespread availability of flexible ureteroscopes and intracorporeal lithotripsy devices, as well as the perception that SWL efficacy with the newest generation of lithotripters is less than with the endourological alternatives. Despite the expanding role in particular for flexible ureteroscopy in the management of upper ureteral calculi, SWL remains a popular therapeutic option for patients [3–5]. Contemporary experience highlights the importance of proper patient selection in achieving successful outcomes with SWL. Technique and the employment of adjunctive measures have also been shown to promote stone fragmentation and stone clearance. In this chapter, the current indications, clinical outcomes, and techniques to enhance efficacy of SWL in the management of ureteral stones are reviewed. Current clinical practice guidelines have emphasized the importance of proper patient selection when considering SWL for an individual patient with a ureteral stone. Stone factors such as size, location, multiplicity, radiopacity, composition (if known), as well as patient factors including body habitus, patient body mass index (BMI), and collecting system anatomy may be useful clues predicting success. Surrogate markers can also be used to help determine whether SWL is worth considering for an individual patient. Hounsfield unit (HU) measurements on computed tomography (CT) scanning can reflect stone hardness and the likelihood of successful fragmentation, which maybe especially useful if stone composition is unknown. Skin‐to‐stone distance (SSD) determined by CT scan provides additional information on the potential impact of patient body habitus on treatment success. The 2016 American Urological Association (AUA)/Endourological Society surgical management of stone guideline emphasized the usefulness of CT in optimizing individual patient treatment while remaining cognizant of radiation exposure risk [6]. CT has the highest accuracy in determining stone size and location and can provide HU and SSD information. Stone burden and individual stone size have well‐known effects on SWL outcomes of renal stones. In a multivariate analysis, renal stones <15 mm in size were associated with a 1.94 times greater chance of clearance post‐SWL than stones larger [7]. As for renal calculi, different cutoffs, ranging from 8 to 12 mm, have been suggested for ureteral calculi [8–10]. Every research group evaluating the influence of variables on success after SWL retained stone size or a surrogate thereof such as stone diameter or surface area as an independent predictor of success [11–17]. Overall, stones larger than 1 cm are considered to have a lower success rate with SWL. Obesity and diabetes have been widely recognized as important risk factors for urinary stone disease with an increasing influence on prevalence [18]. The effect of patient BMI was first highlighted by Pareek et al. who demonstrated that failure of SWL for renal and proximal ureteral stones was associated with an average BMI of 30.8 kg/m2 [19]. The effect of SSD as a surrogate for BMI has been clearly demonstrated in a number of studies. For ureteral stones, however, the literature does not unanimously report a negative impact of a higher SSD [20–22]. Initially, Wiesenthal et al. reported a SSD <11 cm to be a significant predictor of success for renal and ureteral calculi [20]. In a multivariate analysis on the same population, however, evaluating renal and ureteral calculi separately and using SSD as a continuous variable, SSD was no longer a predictor of success for ureteral calculi [12]. Although initially, a 10 cm cutoff for SSD was proposed above which SWL was less successful [19], more recent reports demonstrate a cutoff of 11–12 cm [20, 22, 23]. Whether this is a reflection of the specific geometry of different lithotripters used is unclear. Needless to say, an understanding of the specifications of one’s particular lithotripter is important when considering factors that might affect treatment efficacy. Stone composition has a well‐documented impact on SWL efficacy. Ringdén and Tiselius described stone hardness as a stone’s resistance to shock‐wave therapy, based on the results of SWL of 114 stones treated in vivo [24]. Uric acid/urate, struvite mixed‐infection stones, and calcium oxalate dihydrate stones are most responsive to SWL, followed by, in order of increasing hardness, hydroxyapatite, carbonate apatite, calcium oxalate monohydrate, brushite, and cystine stones [24]. This was similarly identified by Parks and colleagues [25]. Among patients with suspected or known cystine or uric acid stones, SWL is typically not the preferred modality, as they are often poorly visualized on fluoroscopy, making stone targeting problematic. Even if ultrasound targeting is available on the lithotripsy machine, identifying a ureteral stone can be challenging. Cystine stones are typically resistant to SWL fragmentation due to their organic nature. The AUA/Endourology Society guideline based on expert opinion recommends ureteroscopy as the first‐line therapy for patients with ureteral stones and these specific stone compositions requiring treatment [6]. Cystine and calcium oxalate monohydrate stones, in addition to being hard, also tend to break into relatively large pieces that may be difficult to clear from the collecting system [26, 27]. For those patients with the more difficult to fragment stone compositions, SWL should be reserved only for small volume stone burdens [28]. Matrix calculi although relatively soft being composed of predominantly organic matter, also respond poorly to SWL fragmentation efforts [29]. When stone composition is not known, noncontrast CT imaging with measurement of the stone HU value can be a useful proxy. A number of studies have evaluated different HU cutpoints ranging from greater than 750 to 1000 as predictors of SWL failure for ureteral stones [19–22, 30, 31]. In summarizing the current literature, McClain et al. suggest using a liberal estimate of 1000 HU [32], with higher values associated with lower stone fragmentation rates. It is important to realize that most of these papers included both renal and ureteral stones and that these cutoffs may therefore not be completely applicable to ureteral stones. Williams et al. demonstrated that with an increasing collimation width, an increasing underestimation of the HU has to be taken into account due to the volume averaging effect of CT imaging [33]. As most stone protocol CTs apply a 5 mm collimation width, the HU measurements of small stones are most likely an underestimation of the actual stone density [34]. This may explain why the calculated cutoff HU for SWL success is lower than the generally applied 1000 HU in datasets including a large proportion of ureteral stones. Results in the literature are conflicting on whether hydronephrosis has a negative effect on outcomes of SWL for ureteral calculi [13, 16, 35–37]. Recent research indicates that approximately 89% of patients with symptomatic ureteral stones have at least a mild degree of hydronephrosis [38]. The only variable directly correlated with the degree of hydronephrosis was stone size [38]. The degree of obstruction did not appear to have any influence on success rates of SWL for solitary distal ureteral stones in a report by Demirbas et al. [35]. In a cohort of nearly 700 ureteral stones treated by SWL, obstruction appeared to have a negative effect on success, but did not reach statistical significance in a multivariate analysis (odd ratio 1.93, 95% confidence interval [CI] 0.99–3.77, P = 0.053) [16]. Although Seitz and associates identified a success rate of 86.7% for nonobstructing and a 70.5% success rate for obstructing proximal ureteral stones, similarly they could not demonstrate this difference to be statistically significant [36]. El‐Assmy et al. came to the same conclusion, but did identify patients with hydronephrosis to need more SWL sessions to reach stone‐free status and to evacuate fragments after SWL [37]. In an effort to develop a clinical nomogram to predict outcomes after SWL, Kim and colleagues identified hydronephrosis as an independent predictor of failure in a cohort of over 3000 patients [13]. Ureteral wall thickness may be a surrogate for impaction and hydronephrosis and has been demonstrated to decrease success rates of SWL for proximal ureteral calculi [39]. Many variables have been shown to influence stone fragmentation and clearance of fragments after SWL. Although anatomic abnormalities of the urinary tract may not directly influence fragmentation, they may hinder clearance of fragments [40]. Contraindications to SWL of ureteral stones are similar to those for renal stones. Pregnancy remains an absolute contraindication due to the uncertain effects on the fetus [41]. Untreated urinary tract infection (UTI), unrelieved urinary tract obstruction, uncorrected bleeding diatheses, and adjacent arterial aneurysm are other well‐described contraindications [42–44]. Several large series identify the difference in success rates of SWL for ureteral calculi in different locations: 70–97% for proximal stones, 58–97.8% for mid‐ureteral stones, and 54–97.9% for distal ureteral calculi (Table 61.1) [9, 11, 16, 17, 45–47]. Table 61.1 Studies reporting on outcomes of shock‐wave lithotripsy for ureteral calculi in different parts of the ureter. Contemporary series of SWL and ureteroscopy for patients with ureteral calculi describe reasonably high stone‐free rates (SFR) with both modalities. The ability to achieve a stone‐free state with a single procedure was assessed in the 2007 European Association of Urology (EAU)/AUA Guideline for the management of ureteral calculi [48]. For stones in the proximal, middle, and distal ureter the number of ureteroscopy procedures necessary to achieve stone clearance was 1.01, 1.00, and 1.00 respectively. For SWL, the review documented 1.34, 1.29, and 1.26 procedures required for proximal, middle, and distal stones respectively. The 2016 AUA/Endourology Society guideline panel’s meta‐analysis identified superior SFR overall for ureteroscopy over SWL for stones regardless of size and location (90% for ureteroscopy vs. 72% for SWL) [6]. A subanalysis of upper ureteral stones >10 mm in size determined that SFR was comparable (74% for SWL vs. 79% for ureteroscopy). For mid and distal ureteral stones >10 mm, the evidence favored ureteroscopy over SWL (82.5 vs. 67% and 92 vs. 71% respectively). The greater disparity in SFR for mid and distal ureteral stones between ureteroscopy and SWL lead the AUA/Endourology Society guideline panel to give a strong recommendation in favor of ureteroscopy as the first‐line therapy for patients with stones in these specific locations. The updated 2016 EAU guideline recommendations are slightly different and suggest SWL as first‐choice for proximal stones <10 mm and no preference of SWL or ureteroscopy for distal stones <10 mm [49]. The 2016 AUA/Endourological Society guideline on urinary stone management reported the results of a meta‐analysis indicating SWL and ureteroscopy have similar efficacy for stones of varying size in pediatric patients. Pooled success rates were 87 and 95% respectively for stones <10 mm and 73 and 78% for stones >10 mm [6]. These results are confirmed in a large retrospective cohort of pediatric stones, including 1345 ureteral calculi [50]. Although patients needed fewer auxiliary treatments after ureteroscopy (13.6 vs. 18.8%), the authors reported a higher readmission and emergency room visit rates when compared to patients treated with SWL (7.9 vs. 4.9%) [50]. SWL continues to demonstrate lower treatment related morbidity compared to ureteroscopy with a Cochrane review noting a significantly lower complication rate for SWL (relative risk 0.54, 95% CI 0.33–0.88, P = 0.01) [51]. The 2016 AUA/Endourology guideline found no differences in the rates of UTI, sepsis, ureteral stricture, or avulsion between SWL and ureteroscopy; ureteral perforation occurred more commonly during ureteroscopy [6]. Based on a systematic review evaluating the use of antiplatelet/anticoagulation therapy during SWL of renal and ureteral stones, Schnabel and colleagues highlight that bleeding risk of SWL for patients on acetylsalicylic acid has to be weighed against the risk of a cardiovascular event with discontinuation [52]. Whether SWL of ureteral stones is less likely to be associated with bleeding complications for patients who remain on acetylsalicylic acid is unknown. In patients with uncorrected bleeding diatheses or who are unable to discontinue anticoagulation/antiplatelet agents, SWL should still be considered potentially hazardous due to bleeding risks. Ureteroscopy is the recommended treatment modality in these patients [6]. According to the 2016 AUA/Endourological Society guidelines, SWL does not require pretreatment antimicrobial prophylaxis in the absence of a UTI [6]. As demonstrated by a meta‐analysis, antibiotic prophylaxis prior to SWL in low‐risk patients does not confer a lower risk of post‐SWL UTI [53]. The EAU guidelines suggest that in patients with a higher risk of bacterial burden due to presence of an indwelling catheter, stent, nephrostomy tube, or infectious stones, prophylactic antibiotics may be warranted [49]. The safety of SWL for ureteral calculi in children is well established with multiple reports of low complication rates [54–56]. Polat and colleagues demonstrated almost half of the patients >65 years treated with SWL for ureteral or renal calculi to have at least one medical comorbidity [57]. They observed a low major complication ratio (2.1% steinstrasse, 1.2% hematomas, and 0.4% pyelonephritis), concluding SWL to be safe in the elderly population [57]. Theoretical concerns exist about the effects of SWL on the reproductive organs. Among females, the ovaries may be located in the blast path during treatment of distal ureteral calculi, whereas in males, the vas deferens, seminal vesicles, and prostate may be affected. Although in vitro studies suggest spermatozoa are vulnerable to shock‐wave energy, animal studies could not uniformly corroborate these results [58]. Results from clinical trials indicate that there may be a transient decrease in sperm motility and sperm count which resolves by 3 months after the treatment [58]. Although concerns about ovarian effects exist, a decrease in fertility has not been demonstrated in female human subjects who underwent SWL for distal ureteral calculi [59, 60]. SWL for distal ureteral stones should be considered a safe treatment not influencing fertility in patients of reproductive age in either sex. In addition to optimal patient selection for SWL, there are many technical factors that can influence treatment success. It is important to emphasize that technical factors should be optimized at the first SWL attempt. Pace et al. demonstrated that repeat SWL treatments for ureteral calculi unresponsive after the first attempt procure only a limited increase in SFR [46]. The cumulative SFR increased from 68 to 76% with one additional treatment and to 77% with a third treatment [46]. Correct targeting is imperative for achieving SWL success. Although ultrasound guidance can be used for SWL treatment of renal stones, this imaging modality is more challenging for ureteral stones. Fluoroscopic guidance is more commonly employed. For faintly radiopaque or radiolucent stones, a bolus of intravenous contrast can be administered or retrograde ureteropyelogram performed, allowing targeting of the filling defect [61]. In an in vitro SWL study, Olvera‐Posada et al. demonstrated that the interposition of bony structures in the shock‐wave path had a detrimental effect on shock‐wave efficacy [62]. As ureteral stones can overlie the transverse process of lumbar vertebrae, this should be taken into account during patient positioning. In order to avoid interposition of bony structures in the shock‐wave path, Hara and colleagues demonstrated that rotating the patient toward the therapy head increased the success rate significantly for mid‐ and distal ureteral calculi (from 83.9 to 95% and from 89.1 to 98.0% respectively) and a significant decrease in number of SWL sessions for proximal stones [63]. Kose and Demirbas reported higher fragmentation rates with a modified prone position for distal ureteral stones where the obliquely oriented therapy head is positioned on the opposite side of the stone compared to a conventional prone approach (97.5 vs. 89.9% respectively, P = 0.015) [64]. Distal stones can also be targeted in a supine position with the shock‐wave energy directed through the greater sciatic foramen or supine with the therapy head positioned in an over‐patient position (Figure 61.1). The main drawback of a supine approach is the interposition of bony structures, whereas in a prone position bowel gas may attenuate the shock waves and the SSD distance may be higher. A meta‐analysis demonstrated a success rate of 89.6% for the supine position versus 72.7% for the prone position [65]. Phipps et al. achieved a higher success rate with patients in a supine position using a transgluteal shock‐wave path but cautioned that success is operator‐dependent and having the sciatic nerve in the blast path may be painful for the patient [66]. Figure 61.1 Different possible positions for targeting a distal ureteral stone. (a) Supine vertical therapy head, (b) supine oblique therapy head, (c) modified supine, oblique therapy head, (d) prone, vertical therapy head, (e) prone, oblique therapy head, from ipsilateral side, (f) prone, oblique therapy head from contralateral side, (g) modified prone, oblique therapy head from ipsilateral side, (h) supine, over‐patient vertical therapy head, and (i) prone, over‐patient oblique therapy head, from contralateral side. Source: EDAP‐TMS France. Reproduced with permission of EDAP‐TMS France. Recent data suggests that ureteral stones are considerably less influenced by respiratory motion than renal stones, with renal stones moving over a range of 7.7 ± 2.9 mm and ureteral stones over a range of 3.6 ± 2.1 mm [67]. Abdominal compression belts or plates are therefore of limited benefit for treatment of ureteral calculi. In vitro and clinical research has demonstrated that air bubbles caught in the coupling gel of the therapy head have a detrimental effect on SWL efficacy [68, 69]. Tailly et al. demonstrated that a camera incorporated in the therapy head can help evaluate the coupling area, creating awareness of the presence of air bubbles and prompting manual removal [70]. Azm and Higazy were the first to report a beneficial effect of forced diuresis on SWL outcomes especially for distal ureteric stones [71]. Whereas Zomorrodi and colleagues achieved similar results [72], Tiselius and colleagues demonstrated no difference in SWL success with or without forced diuresis, but suggest diuresis is still worthwhile post‐SWL [73, 74]. Medical expulsive therapy (MET) as the initial management option for ureteral calculi is controversial as a recent large randomized controlled trial (RCT) contradicted a previously published meta‐analysis [75, 76]. Skolarikos and colleagues performed a systematic review on the use of MET after SWL to improve clearance of fragments and pooled the results of 26 trials [77]. Their results endorse the use of MET, mainly alpha‐blockers, to improve clearance rate and clearance time after SWL [77]. Eryildirim and associates additionally reported that MET post‐SWL for ureteral calculi could increase patients’ quality of life [78]. According to the most recent AUA/Endourological Society stone guidelines, routine stenting should not be performed in patients undergoing SWL [79]. This recommendation is based on a meta‐analysis published in 2011 that included eight studies and 876 patients [80]. Although no difference was noted for success rate after SWL, the review did show a benefit of reducing the steinstrasse rate with stenting [80]. This result was largely influenced by one study including 400 patients with renal stones measuring 1.5–3.5 cm [81]. Several studies have even shown a significantly reduced treatment success after SWL for ureteral stones in stented patients [16, 45, 46, 82]. Pooling data from seven studies, Picozzi et al. performed a meta‐analysis on the differences between emergent and delayed SWL for ureteric stones [83]. Out of the three included RCTs, only Tombal et al. demonstrated that immediate SWL significantly improved SFR for proximal ureteral stones as determined at 48 hours after treatment [84–86]. A shorter hospital stay as well as the need for fewer auxiliary procedures are some of the reported benefits of emergent SWL [85, 86]. Although underpowered, a recent RCT corroborated these findings with a success rate of 93.8% for immediate versus 80% for delayed SWL [87]. The pathophysiology accountable for this phenomenon is hypothesized to be a lack of edema in the early stages of ureteric colic, which may allow an expansion chamber to form, enhancing fragmentation [83, 88]. Zhou et al. demonstrated that a stepwise increase of voltage procures the best comminution results in in vitro and animal experiments [89, 90]. This phenomenon was verified in a clinical RCT including 50 patients with upper tract urinary calculi up to 2 cm, including 20 ureteral calculi [91]. The only RCT on voltage ramping for ureteral calculi did not demonstrate an advantage over fixed voltage SWL [92]. During SWL treatment of proximal ureteral calculi, renal parenchyma may be in the blast path of the shock wave. As several authors have reported voltage ramping to decrease the chance of renal hematoma, this should be taken into account when treating stones in this location [82, 93]. When SWL is not performed under general anesthesia or conscious sedation, Berwin et al. suggested that voltage ramping is additionally of importance for pain tolerance during the treatment [94]. When treating a ureteral stone under general or conscious sedation, without having any renal parenchyma in the blast path, voltage ramping seems to be of minimal benefit. There is extensive in vitro and in vivo research experience endorsing a low‐voltage pretreatment to improve stone fragmentation and decrease damage to renal parenchyma [95–98]. The most recent report would indicate that 300 shocks at low voltage without a pause has the best renoprotective effect while improving fragmentation [98]. Although clinical data is lacking for ureteral stones, pretreatment can be taken into account when renal parenchyma is in the blast path when treating upper ureteral calculi. The superiority of a slower shock‐wave rate on treatment efficacy has been demonstrated both in vitro and in vivo. Greenstein and Matzkin initially identified a 1 Hz shock‐wave rate to be most efficient for stone comminution in an in vitro setting [99]. Paterson et al. corroborated these results in an in vivo porcine model, demonstrating that a 0.5 Hz shock‐wave rate produced better stone comminution than a frequency of 2 Hz [100]. Utilizing the same in vivo model, Connors and colleagues later demonstrated that a shock‐wave rate of 1 Hz had a smaller negative effect on glomerular filtration rate(GFR) and renal plasma flow when compared to a 2 Hz regimen, without applying a pretreatment, treatment pause, or voltage ramping [101]. A meta‐analysis including 2144 patients from 13 RCTs demonstrated slower shock‐wave rates of 1–1.5 Hz to have a superior success rate as compared to 2 Hz, without a significant difference in complication rate [102]. Pooled data analysis, however, could only identify this beneficial effect for stones larger than 10 mm, whereas the shock‐wave rate did not seem to influence the success rate for smaller stones [102]. Although this meta‐analysis included treatment of 738 ureteral stones from seven studies, of which 339 were treated at a low shock‐wave rate, 247 at a intermediate shock‐wave rate, and 152 at a high shock‐wave rate, a subgroup analysis was not performed [103]. Several groups have focused on differences in shock‐wave rate effect on ureteral stones alone [104–106]. Whereas Honey and colleagues demonstrated the benefit of a slow shock‐wave rate for proximal ureteral stones, Anglada‐Curado et al. have shown a slow shock‐wave rate to be superior in a cohort of distal ureteral stones. In contrast to the results of these two trials, Nguyen et al. found a shock‐wave rate of 1.5 Hz to result in a higher success rate when compared to 1 Hz [104]. It should be noted that most stones included in this study were smaller than 10 mm in diameter and that analysis could not demonstrate a difference in effect for distal stones [104]. See Box 61.1.
Shock‐wave Lithotripsy of Ureteral Calculi
Introduction
Current indications for shock‐wave lithotripsy of ureteral stones
Outcomes
Proximal, mid, and distal ureteral locations
Study
n
Ureteropelvic junction
Proximal
Mid
Distal
Ureterovesical junction
Total
Pace 2000 [46]
1593
755/1071 (70%)
232/340 (68%)
99/182 (54%)
1086/1593 (68%)
Delakas 2003 [16]
688
262/316 (82.9%)
59/78 (75.6%)
181/294 (61.5%)
502/688 (73.0%)
Gomha 2004 [17]
984
110/127 (86.6%)
466/481 (96.9%)
40/42 (95.2%)
302/334 (90.4%)
918/984 (93.3%)
Kanao 2006 [11]
292 (ureteral only)
147/186 (79.0%)
25/33 (75.8%)
56/73 (76.7%)
228/292 (78.1%)
Tiselius 2008 [47]
580
244/254 (96.1%)
88/90 (97.8%)
231/236 (97.9%)
563/580 (97.1%)
Sfoungaristos 2012 [45]
156
12/15 (80%)
32/45 (71.1%)
25/43 (58.1%)
37/39 (94.9%)
14/14 (100%)
120/156 (76.9%)
Demirbas 2012 [9]
2836
742/871 (85.1%)
262/312 (83.9%)
1462/1653 (88.4%)
2466/2836 (87%)
Total
7129
122/142 (85.9%)
2648/3224 (82.1%)
731/938 (77.9%)
2368/2811 (84.2%)
14/14 (100%)
5883/7129 (82.5%)
Pediatric stones
Treatment safety
Strategies to enhance efficacy
Imaging guidance
Patient positioning
Respiratory motion
Coupling
Diuresis
Medical expulsive therapy
Stenting
Treatment timing
Treatment protocol
Voltage ramping
Pretreatment and pause
Shock‐wave rate
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