Problems with Residual Stones

Noah E. Canvasser & Margaret S. Pearle

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

Introduction

Recent epidemiologic studies show that the prevalence of nephrolithiasis is rising. In the United States, nearly 9% of the population will be diagnosed with a stone in their lifetime [1], with comparable increases in prevalence seen in European and Asian countries [2]. Accordingly, cost estimates for the diagnosis and treatment of stone disease in the United States are projected to increase substantially, from US$3.79 billion/year in 2007 to US$5.03 billion/year in 2030 [3]. Because of this, efforts to improve the efficiency of stone care are imperative.

Although nearly all patients with stones requiring treatment are now managed initially by noninvasive or minimally invasive means, and open surgery has all but disappeared [4], the need for secondary procedures to remove persistent stones or residual fragments (RFs) has increased. In this chapter, we review the outcomes of patients left with RFs after minimally invasive stone interventions, including shock‐wave lithotripsy (SWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL).

Shock‐wave Lithotripsy

Although the introduction of SWL in 1980 by Chaussy et al. revolutionized the management of stone disease [5], it also brought with it a new management challenge – what to do with fragmented stones that fail to pass spontaneously. Although early reports documented high SWL treatment success rates, 20–30% of patients were left with ≤4–5 mm RFs [6, 7]. The term “clinically insignificant residual fragments” (CIRFs) was coined to denote small fragments that were expected to ultimately pass spontaneously and were considered a benign consequence of stone fragmentation. Indeed, Moon and Kim reported stone‐free rates (SFRs) of 33%, 73%, and 93% at 1, 3, and 6 months, based on kidney–ureter–bladder (KUB) radiographs post‐SWL among 248 patients with small RFs, validating the assumption that most small fragments eventually pass [8]. These authors concluded that practitioners should wait six months after SWL before offering repeat or secondary treatment.

Buchholz and associates also found a high rate of fragment clearance after SWL [9]. Among 55 patients with <5 mm RFs, 88% were stone free at a mean of 2.5 years after SWL. Likewise, Osman et al. found that 79% of 173 patients with ≤4 mm RFs after SWL cleared their RF within six months of SWL [10]. However, other studies have been less optimistic about fragment clearance. El‐Nahas et al. used computed tomography (CT) to follow 154 patients left with ≤5 mm RFs at over three months after SWL and found that only 13% of patients had cleared their fragments at a mean of 31 months [11].

Streem et al. were the first to recognize that not all small RFs after SWL remain inert [12]. They identified 160 patients treated with SWL who were left with ≤4 mm RFs and found that 43% experienced a symptomatic event and/or required surgical intervention at a mean of 26 months following treatment. By Kaplan–Meier analysis, the 5‐year probability of becoming symptomatic or requiring surgery was 71% and the probability of stone growth was 20%, indicating that RFs can have significant consequences.

Since the report by Streem et al., other investigators have likewise reported on the natural history of RFs after SWL and found that they can be a significant source of morbidity. Khaitan et al. prospectively followed 75 patients with ≤4 mm RFs identified on abdominal radiographs obtained three months after SWL and found that at a mean follow‐up of 15 months, 24% of patients cleared their fragments. However, among the 57 patients who retained their RFs, 72% demonstrated growth of the fragments, 61% experienced pain, and 42% required surgical intervention [13]. Osman et al. reviewed a series of 173 patients with RFs post‐SWL and found that 21.4% of patients in whom there was growth of the fragments required surgical intervention at a mean of 4.9 years [10]. El‐Nahas et al. followed 154 patients with RFs for a mean of 31 months, and noted that nearly half (48.7%) required surgical intervention or needed pain medication due to progression or movement of the RFs [11]. Finally, Candau et al. reviewed 83 patients with ≤4 mm RFs identified on three‐month post‐SWL imaging and found that at a medium follow‐up of 40.6 months, 37% of patients demonstrated an increase in stone size by nephrotomogram imaging, and 58% of those patients underwent secondary treatment [14].

In contrast, Buchholz et al. followed 44 patients with ≤5 mm RFs after SWL for a mean of 33 months and found that only 12.5% of patients retained those fragments at the end of the period of observation and no patients experienced pain with stone passage [9]. Furthermore, only 2.1% of patients showed an increase in stone size.

Factors associated with an adverse outcome as a consequence of small RFs has been investigated. Although Candau et al. failed to identify any variables associated with clinically significant outcomes [14], other investigators reported that larger fragment size and/or greater stone burden correlated with worse outcomes [10, 11, 13]. In addition, RF location likely plays a role, as renal pelvic fragments tend to pass spontaneously [13], whereas calyceal, particularly lower pole, stones have lower clearance rates [10, 13]. Sahin et al. identified 80 patients with RFs after SWL and divided them into those with ≤2 mm (n = 30), 2– ≤ 4 mm RFs (n = 21), and >4 mm RFs (n = 35) [15]. Fragment clearance occurred in 100% of patients with ≤2 mm RFs, 76% of patients with 2– ≤ 4 mm RFs and 52% of patients with >4 mm RFs within three months. Moreover, emergency department (ED) visits were required in 19% and 51% of patients with 2– ≤ 4 mm and >4 mm RFs, respectively, compared to no ED visits in patients with ≤2 mm RFs. Accordingly, quality of life assessment using the SF‐36 survey demonstrated that larger RF size was associated with significantly lower scores at one month and three months following SWL.

Considering the totality of these studies, growth of RFs after SWL occurred in 29% of patients, 25% of patients became symptomatic as a result of their RFs, and 33% of patients with RFs required intervention (Table 37.1). However, there are several limitations in comparing these natural history studies. Differences in imaging modalities result in differences in the sensitivity of detecting RFs. Furthermore, the definition of small RF after SWL is variable and has included ≤4 mm [12–14] and ≤5 mm [9–11]. Regardless, the literature has been reasonably consistent in identifying adverse outcomes in more than a quarter of patients with RFs after SWL.

Table 37.1 Outcomes of residual fragments after shock wave lithotripsy.

Author (year)	No. of patients	RF size (mm)	Mean follow‐up	Imaging	Asymptomatic	Passed	Stone growth	Symptomatic	Intervention
Streem (1996) [12]	160	≤4	23 months	KUB/US	56.9% (91/160)	23.8% (38/160)	18.1% (29/160)	25.6% (44/160)	27.5% (41/160)
Buchholz (1997) [9]	44 (94 RF)	≤5	2.5 years (median)	KUB	12.5%	87.5%	2.1% (2/94)	0.0% (0/94)	0.0% (0/94)
Candau (2000) [14]	83	≤4	40.6 months (median)	KUB	–	33.0% (27/83)	37.0% (31/83)	–	22.0% (18/83)
Khaitan (2002) [13]	75	≤4	15 months	KUB/IVP/US	17.3% (13/75)	24.0% (18/75)	54.7% (41/75)	46.7% (35/75)	32.0% (24/75)
Osman (2005) [10]	173	≤4	4.9 years	IVP/RGP/US	–	78.6% (136/173)	21.4% (37/173)	–	43.9% (76/173)
El‐Nahas (2006) [11]	154	≤5	31.3 months	CT	–	13.6% (21/154)	33.8% (52/154)	14.9% (23/154)	33.8% (52/154)
Total	689	–	–	–	44.3%*	37.3%*	29.4%*	25.4%*	33.2%*

^a Excludes Bucholz et al. because denominator indicated RFs instead of patient/renal units.

RF, residual fragment; KUB, kidney–ureter–bladder; US, ultrasound; IVP, intravenous pyelogram; RGP, retrograde pyelogram.

Ureteroscopy

Historically, series of URS for intrarenal calculi have demonstrated high SFR, ranging from 77 to 91% [16–18]. With further improvement in URS technology, progressively larger renal calculi have been addressed, with reported SFRs of approximately 85% in series of patients with >2 cm stones [19, 20]. However, these early URS series relied on abdominal radiography and/or ultrasonography to assess stone‐free status, imaging modalities known to be inferior to CT for detecting RFs. Furthermore, the fate of RFs after URS was not typically assessed.

In a multicenter randomized controlled trial (RCT) comparing URS and SWL for the treatment of patients with ≤1 cm lower pole stones, Pearle et al. used three‐month CT to determine SFRs and found sobering outcomes for both modalities: 35% for SWL and 50% for URS [21]. More contemporary series have likewise validated lower SFRs for URS than previously reported. Portis et al. prospectively evaluated 69 patients undergoing URS for 5–15 mm renal or proximal ureteral calculi who were imaged with CT one month post procedure [22]. Among 58 patients who completed follow‐up, the mean CT SFR was 53.6%. Furthermore, at mean follow‐up of 1.4 years, 5.2% of patients underwent repeat endoscopic intervention. Macejko et al. reviewed 92 patients who underwent 119 ureteroscopic procedures for renal or ureteral calculi and reported an SFR by CT of 50.4% [23]. When stratified by stone location, the SFR for stones in the kidney only was 34.8% compared with 80% for stones located in the ureter only. Rippel et al. also reviewed 265 URS procedures among 248 patients who were imaged with CT postoperatively and found an SFR of 62% [24]. On multivariate analysis, they determined that only pretreatment stone diameters of 6–10 mm (OR 2.03, 95% confidence interval (CI) 1.07–3.84, P = 0.03) and >10 mm (OR 3.74, 95% CI 1.57–8.94) were independent predictors of RFs.

The low SFR after URS revealed by CT in these studies underscores the need to understand the fate of these RFs. Several investigators have evaluated the natural history of RFs after URS. Rebuck et al. reviewed 330 URS procedures among 307 patients and identified 46 patients with 51 renal units containing ≤4 mm RFs [25]. Restricting their analysis to only those with calcium‐based stones, these investigators determined the outcome of these patients out to a mean follow‐up of 18.9 months. They found that 22% of patients passed their fragments, 59% remained asymptomatic with retained fragments, and 20% experienced a stone‐related event (SRE) (ED visit, hospitalization, or intervention) at a mean of 27 months post operatively. In addition, they noted that asymptomatic stones tended to demonstrate minimal growth (from 2.7 mm at three months to 3.0 mm at 33 months), while patients who experienced an SRE demonstrated growth of RFs from 2.5 mm at three months to 6.3 mm at 27 months, suggesting perhaps that stone growth portends increased risk of an SRE.

Ozgor et al. also followed 44 patients with ≤5 mm RFs detected on CT within three months of URS with annual CT imaging [26]. At a mean of 30.5 months follow‐up, 66% of patients either passed their RFs or remained asymptomatic with no stone progression. However, stone growth was detected in 11% of patients, 23% experienced symptoms, and surgical intervention was required in 25%.

Portis et al. used need for repeat surgery as the primary outcome parameter in a retrospective review of 226 URS procedures in 217 patients for one or more renal or ureteral calculi for which no individual stone exceeded 15 mm in size [27]. SFR (by CT in 71% of renal units) at one month following stent removal was 53%. At a median follow‐up of 4.1 years, 8.7% of patients (n = 19) underwent repeat surgery, including 14 URS and 5 PCNL procedures. By Kaplan–Meier analysis, the repeat surgery rate at 1 and 5 years was 5.8% (95% CI 3.4–9.8) and 8.6% (95% CI 5.6–13.1), respectively. The need for repeat surgery correlated strongly with the size of the RF (P < 0.001). When outcomes were stratified by RF size, need for repeat surgery at 1 and 5 years was 2.3% and 3.5%, respectively, for patients with no RFs; 20.8% at both 1 and 5 years for patients with RFs of >2– ≤ 4 mm; and 30.1% and 46.2%, respectively, for patients with RFs of >4 mm. For patients with ≤2 mm RFs, 1‐ and 5‐year cumulative repeat surgery rates were low at 1.6% and 2.5%, respectively, but higher at 8.5% at both 1 and 5 years for patients with ≤4 mm RFs. Consequently, although patients with RFs ≤2 mm in size rarely required repeat surgery, those with RFs >2 mm were at substantially greater risk.

The largest series to date evaluating the fate of small RFs after URS is a multicenter retrospective review from Chew et al., representing the Endourology Disease Group for Excellence (EDGE) consortium [28]. This group identified 232 patients who underwent URS at one of six centers and were left with RFs of any size. At a mean follow‐up of 16.8 months, 44% of patients experienced an SRE, defined as stone growth, stone passage, need for reintervention, or complication, and 29% underwent surgical intervention. When outcomes were stratified by RF size, they found that stone passage rates were comparable between those with RFs ≤4 mm and those with RFs >4 mm (26–27%). However, larger fragments were more likely than smaller fragments to demonstrate stone growth (59% vs. 28%, respectively, P < 0.001), to require intervention (38% vs. 18%, respectively, P = 0.01) and to be associated with complications (59% vs. 22%, respectively, P = 0.039).

Overall, taking into account three natural history series comprising 322 patients, 38% of patients experienced pain or an SRE and 26% of patients required surgical intervention (Table 37.2). Multivariable analyses have demonstrated that stone growth and the occurrence of symptomatic events after URS are associated with non‐lower pole calyceal location [25], preoperative stone burden [24, 26]

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