Assessment of Residual Stone Fragments After Retrograde Intrarenal Surgery

Abstract

Objectives:

To define the most suitable approach to assess residual stone fragments after retrograde intrarenal surgery (RIRS).

Methods:

Ninety-two patients (115 renal units) submitted to RIRS for symptomatic kidney stones >5 mm and <20 mm or <15 mm in the lower Calyx diagnosed by noncontrast CT (NCCT) were prospectively studied. Residual fragments were assessed by endoscopic evaluation (END) at the end of the procedure and by NCCT, ultrasonography (US), and kidney, ureter, and bladder radiograph (KUB) on the 90th postoperative day (POD). NCCT was considered the gold standard for the evaluation of residual fragments after RIRS.

Results:

The 90th POD NCCT resulted in stone-free status in 74.8% (86/115), 0–2 mm in 8.7% (10/115), and >2 mm residual fragments in 16.5% (19/115) renal units. Stone-free status by END at the end of RIRS was coincident with NCCT in 93.0% of the cases (40/43). There were no cases of residual fragments >2 mm on NCCT if END resulted in stone-free status. In all cases where END resulted in residual fragments >2 mm, US proved to be correct according to NCCT. Neither US nor KUB was able to identify residual fragments between 0 and 2 mm. KUB had only 31.6% (6/19) sensitivity to detect residual fragments >2 mm and did not add sensitivity or specificity to US.

Conclusions:

In the follow-up imaging after RIRS, we suggest that if END resulted in residual fragments <2 mm, a 90th POD NCCT should be performed. US may be used if END showed fragments >2 mm.

Introduction

Retrograde intrarenal surgery (RIRS) is being widely used for the treatment of kidney stones of up to 20 mm with high stone-free rates and low morbidity.¹ However, residual fragments after RIRS can cause pain and obstruction leading to additional procedures.² Residual fragment assessment is mandatory but neither the timing nor the modality of image study is standardized yet.¹

Noncontrast CT (NCCT) has become the gold standard for diagnosing urinary stones.¹ Stone-former patients are submitted to several NCCT studies owing to stone-related events and the recurrent nature of urinary stone disease. However, the cumulative exposure to the ionizing radiation of NCCT may be harmful and induce tumors.^2,3 Therefore, efforts to reduce radiation exposure are recommended, such as best timing to submit the patient to NCCT, low-radiation dose protocols, and restriction of the region of the body to be examined.^4

–7

According to the current literature, up to 38% of the renal units may have residual fragments >2 mm after RIRS when assessed by NCCT.⁸ Other modalities for evaluating residual fragments such as surgeon endoscopic evaluation (END) at the end of the procedure, ultrasonography (US), and kidney, ureter, and bladder radiograph (KUB) have been used to avoid NCCT in patients submitted to RIRS.⁹ The aim of this study was to define the most suitable approach to assess residual fragments after RIRS.

Methods

From August 2016 to August 2017, consecutive symptomatic adult patients, with NCCT-diagnosed kidney stones of >5 mm and <20 mm or <15 mm in inferior calix were provided treatment by RIRS. Multiple and bilateral kidney stones were included in the study. Residual fragments were assessed at the end of the procedure by END and on the 90th postoperative day (POD) by NCCT, US, and KUB on the same day in all patients who were submitted to RIRS. END, US, and KUB results were compared against NCCT. The study protocol was approved by our hospital's ethics committee and written informed consent was obtained from all patients submitted to RIRS according to the ethical principles for medical research involving human subjects of the Declaration of Helsinki.

Patients with kidney malformations, ureteral stenosis, previous ipsilateral endoscopic or open kidney procedure, hydronephrosis, indwelling Double-J stent, and contraindications for RIRS were excluded. Patients with multiple and bilateral kidney stones were included. Our intention was to study a population as close as possible of the index patient who came to the office for a flexible ureteroscopy. Moreover, these features might impact on surgical outcomes by different diagnostic tools.

All procedures were performed under general anesthesia in a standardized method by the same surgeon (A.D.).

A Nitinol 0.035 inch guidewire (Coloplast, Denmark) and a PTFE 0.035 inch guidewire (Coloplast) were inserted up to the renal pelvis under fluoroscopic guidance. Semi-rigid ureteroscopy was performed as an initial step in all procedures. In every case, ureteral sheath 10/12F × 35 cm (Coloplast) was then placed up to the upper ureter and the flexible ureteroscope (URF-P5^®; Olympus, Japan) was inserted for direct inspection of all renal calices before lithotripsy.

Laser lithotripsy was performed with a 270 μm Holmium laser fiber (Dornier) using 12 Hz and 0.6 J laser settings. Stone fragments >2 mm were removed with a 1.5F tipless basket (Coloplast). Stone fragment size was compared with the guidewire and if equal or less in diameter were left behind. At the end of fragmentation, small fragments were irrigated from the inferior calix to the renal pelvis. Pyelography through the ureteral sheath was performed at the end of the procedure and a 6F silicone Double-J stent (Coloplast) with an external string was located. The ureteral sheath was removed under direct ureteroscopic vision. Patients were maintained under analgesics and antibiotics until Double-J stent removal on the 10th POD.

Residual fragments were assessed by END at the end of RIRS and by NCCT, US, and KUB at 90th POD in all patients. NCCT was considered the gold standard for residual stone fragment evaluation. The sum of all residual fragments' largest diameter was considered as the final size for this study. Residual fragments were categorized as 0 when no residual fragment exists, 0–2 mm, and >2 mm. END considered the guidewire width, 0.89 mm, as a comparative parameter to estimate the size of residual fragments.

NCCT was performed using a 64-slice GE Lightspeed CT Scanner^® (General Electric^®) with a slice thickness of 1 mm and radiation low-dose protocol (low tube charge current, 60 mA) in patients with body mass index (BMI) <30 kg/m² and standard protocol (160 mA) in patients with >30 kg/m². NCCTs were evaluated in the magnified bone window (400%, width, 1600 HU/level, 500 HU) in three axes. NCCT and KUB were evaluated by a senior radiologist (B.A.R.) blinded to the procedure and US results. US was performed by a different senior radiologist (A.C.) using hardware Aplio Toshiba XG^® (Toshiba^®, Japan) blinded to the results of the procedure and NCCT.

Surgical complications were recorded based on Clavien–Dindo classification during 90 days of follow-up.¹⁰

Statistics

Sample size was calculated based on the percentage of renal units with residual fragments >2 mm by NCCT of 38%.⁸ Therefore, the sample size for a bicaudal test with significance level of 5% and test power of 95% is 115 renal units.

SAS 9.0 program^® (SAS Institute Inc., Cary, NC) was used to compare NCCT against END, US, and KUB by Cochran's Q test with a significance level of 5%.

Results

From August 2016 to August 2017, 92 patients were successfully submitted to RIRS. Bilateral procedures were performed in 23 patients (25%) resulting in 115 renal units being operated. Clinical data are summarized in Table 1. Stone features evaluated by NCCT are given in Table 2. Postoperative NCCT revealed stone-free status in 74.8% (86/115), 0–2 mm in 8.7% (10/115), and >2 mm residual fragments in 16.5% (19/115) renal units. END, US, KUB, and US + KUB were compared against NCCT to obtain sensitivity, specificity, positive predictive value, and negative predictive value of these methods (Table 3). Table 4 provides the distribution of residual fragments results among the methods of evaluation.

Table 1.

Clinical Data of 92 Patients Submitted to Retrograde Intrarenal Surgery

Gender, female (%)	60 (65.2)
Age (mean ± SD, range), years	46.8 ± 14.1, 18–79
BMI (mean ± SD, range), kg/m²	28.1 ± 4.8, 19.0–45.5
ASA, n (%)
I	38 (41.3)
II	44 (47.8)
III	10 (10.9)
Charlson, n (%)
0	36 (39.1)
1	18 (19.6)
2	17 (18.5)
3	7 (7.6)
4	7 (7.6)
5	2 (2.2)
6	1 (1.1)
7	2 (2.2)
8	1 (1.1)
9	0 (0.0)
10	1 (1.1)
Bilateral, n (%)	23 (25.0)

ASA, American Society of Anesthesiologist; BMI = body mass index; SD = standard deviation.

Table 2.

Stone Features of the 115 Renal Units Submitted to Retrograde Intrarenal Surgery

Stone features
Multiple stones (%)	69 (60.0)
Largest diameter size (mean ± SD, mm)	7.92 ± 3.81
Total volume (mean ± SD, mm³)	435.5 ± 472.7
Density (mean ± SD, HU)	989.4 ± 330.2
Diverticulum/hydrocalix, n (%)	8 (2.9)
Inferior calix, n (%)	100 (36.2)
Medium calix, n (%)	76 (27.5)
Superior calix, n (%)	68 (24.6)
Renal pelvis, n (%)	24 (8.7)

Table 3.

Comparison Between Methods and Noncontrast CT for Detection of Residual Fragments

	NCCT
	0 mm				0–2 mm				>2 mm
	Sens. (%)	Spec. (%)	PPV (%)	NPV (%)	Sens. (%)	Spec. (%)	PPV (%)	NPV (%)	Sens. (%)	Spec. (%)	PPV (%)	NPV (%)
END
0 mm	89.7	46.5	36.1	93.0
0–2 mm					22.2	89.8	25.0	88.3
>2 mm									55.0	93.7	64.7	90.8
US
0 mm	89.7	74.4	54.2	95.5
0–2 mm					0.0	100.0	—	92.2
>2 mm									95.0	69.5	39.6	98.5
KUB
0 mm	20.7	100.0	100.0	78.9
0–2 mm					0.0	100.0	—	92.2
>2 mm									25.0	98.9	83.3	86.2
US + KUB
0 mm	89.7	74.4	54.2	95.5
0–2 mm					0.0	100.0	—	92.2
>2 mm									95.0	69.5	39.6	98.5

END = endoscopic evaluation; KUB = kidney, ureter, and bladder radiograph; NCCT = noncontrast CT; NPV = negative predictive value; PPV = positive predictive value; Sens. = sensitivity; Spec. = specificity; US = ultrasonography.

Table 4.

Distribution of Residual Fragments After Retrograde Intrarenal Surgery Among Methods Using Noncontrast CT as Gold Standard

Method	NCCT			Total
Method	0	0–2 mm	>2 mm	Total
END
0	40	3	0	43
0–2 mm	44	3	8	55
>2 mm	2	4	11	17
US
0	64	2	1	67
0–2 mm	0	0	0	0
>2 mm	22	8	18	48
KUB
0	86	9	14	109
0–2 mm	0	0	0	0
>2 mm	0	1	5	6
Total	86	10	19	115

Stone-free rate by END at the end of RIRS was 37.4% (43/115) renal units and the postoperative NCCT showed that the END for stone-free state was correct in 93.0% (40/43). However, the specificity for stone-free state was low at 46.5% (40/86). There were no cases of residual fragments >2 mm on NCCT when END was stone free. Residual fragments were noted in 62.6% (72/115) renal units at END but only in 25.2% (29/115) at 90th POD NCCT.

Neither US nor KUB identified residual fragments between 0 and 2 mm. US misdiagnosed stone-free renal units as residual fragments >2 mm in 25.6% (22/86). However, if US was stone free, the result was correct in 95.5%. In the 17 renal units that END described residual fragments >2 mm, US was correct in all cases according to NCCT. KUB was not able to add sensitivity or specificity to 90th POD US.

In addition, we performed a multivariate analysis to search for determinants of stone-free status and residual stone fragments <2 mm at POD 90 NCCT (Appendix Table 1). Stone diameter was a significant factor for stone-free state (p = 0.007; 95% confidence interval [CI] = 0.507–0.897). Stone diameter and HU were significant factors for residual stone fragments <2 mm (p = 0.005; 95% CI = 1.189–2.607 and p = 0.018; 95% CI = 0.992–0.999, respectively).

Of 92 patients, Clavien–Dindo postoperative complications grades I, II, and IIIa occurred in 14 cases (15.2%) for requiring analgesic, 5 (5.4%) owing to urinary tract infection, and 1 (0.1%) as a result of ureteral stent placement. During follow-up, 16 patients visited the emergency room (16/92, 17.4%). One patient visited four times for analgesics, six patients visited twice, and nine patients visited once. All patients were kept enrolled and followed according to the study design. The 90th POD NCCT and US revealed one asymptomatic small subcapsular hematoma in a stone-free renal unit and two asymptomatic hydronephrosis, one in a stone-free renal unit and other in a renal unit with >2 mm residual fragment. Both cases were further investigated with Diethylenetriaminepentaacetic acid renogram that resulted in no urinary obstruction.

Discussion

Follow-up imaging after RIRS is crucial to assess residual fragments, hydronephrosis, and complications such as perirenal hematoma, urinoma, and obstruction of the urinary system.¹¹ To date, there is no consensus as to which image modality should be used for the follow-up patients after RIRS. Although low-dose NCCT is the current gold standard for the evaluation of urinary stone disease because of its high sensitivity and specificity equivalent to the standard NCCT,^6,12 some authors still assess stone-free rate by KUB and US¹³ and recent data showed that only ∼25% of ureteroscopy patients receive at least one postoperative CT within a year.¹⁴ Moreover, 55% and 39% of ureteroscopy patients received no postoperative imaging within 3 and 12 months, respectively.¹⁴

On the contrary, NCCT radiation exposure and cost are a serious concern. Low-dose NCCT radiation exposure is roughly four times more than that of KUB and up to 20% of stone-former patients may be submitted to more than the safe threshold of exposure of 50 mSv during the first year of follow-up.¹⁵ Moreover, low-dose NCCTs are <8% of all CTs for the evaluation of kidney stones, showing a disturbing underuse.¹⁶ Besides, NCCT is typically 10-fold more expensive than a plain radiograph and 2-fold than US.¹⁷

This study prospectively compared different methods for the evaluation of residual fragments after RIRS to look for different scenarios where NCCT could be spared.

We used low-dose NCCT with 60 mA in nonobese patients (BMI <30 kg/m²) and NCCT with 160 mA in obese patients as the gold standard for this study to minimize the radiation exposure without compromising on image quality.^18,19 NCCT image noise varies proportional to the value of the square root of the milliampere product. Higher noise from ultra-low-dose NCCT (<30 mA) may decrease accuracy in detecting small residual fragments (<3 mm).²⁰ Magnified bone window NCCT should be preferred for urinary stone evaluation because of better image quality for dense objects as it minimizes noise artifacts close to the stone limit.^20,21

Among 115 renal units submitted to RIRS, 74.8% (86/115) were rendered stone free on 90th POD NCCT. To determine sensitivity, specificity, positive predictive value, and negative predictive value, we compared END at the end of the procedure, US, and KUB with NCCT. END of residual fragments used the guidewire width as standard. Other disposables might be used for comparison purposes. However, we do not recommend laser fiber because diameter varies and is not reliable.²²

Stone-free status at the END was confirmed by NCCT in 93.0% and no fragments >2 mm were found on NCCT when END was stone free. Therefore, a meticulous END is of paramount importance at the end of RIRS.

Residual fragments were noted in 62.6% (72/115) renal units at END but only in 25.2% (29/115) at 90th POD NCCT, resulting in a clearance rate after 90 days of 59.7% (43/72). Most of the endoscopic residual fragments between 0 and 2 mm turned stone free on 90th POD NCCT (80.0%, 44/55). Therefore, it is reasonable to delay the first imaging follow-up study to POD 90.

US overestimates stone size compared with NCCT.^18,23 Our study showed that US misdiagnosed stone-free renal units as having residual fragments >2 mm in 25.6% (22/86). However, the finding of stone free by US has a high negative predictive value of 95.5% and was concordant to NCCT in all cases when the END showed residual fragments >2 mm.

Follow-up image is important not only for the assessment of residual fragments, but also for the evaluation of surgical complications.¹¹ Our study showed concordant findings between NCCT and US: one small subcapsular hematoma and two asymptomatic hydronephrosis. The small number of complications prevents further analysis for the best image modality to look for surgical complications.

Our study has several strengths. It is a prospective study using low-dose bone window NCCT as gold standard for residual fragments after RIRS, providing more accurate results. To the best of our knowledge this is the first study to prospectively address follow-up image specifically for RIRS performed in patients with solely kidney stones and no previous ureteral instrumentation. All patients were submitted to NCCT, US, and KUB on the same day by radiologists blinded to END and other image modality results. However, it is a single center study and our results should be validated by other high volume centers.

Conclusion

In the follow-up imaging after RIRS, we suggest that if END shows stone free or residual fragments between 0 and 2 mm, a low-dose NCCT should be performed. US is enough if END shows residual fragments >2 mm.

Footnotes

Acknowledgment

FAPESP 2014/05130-2.

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

Appendix

Appendix Table 1.

Predictors of Residual Fragments After Retrograde Intrarenal Surgery

Features	Mean ± SD (95% CI)		Univariate p-value		Multivariate p-value
Features	Stone free	<2 mm	Stone free	<2 mm	Stone free	<2 mm
N stones	2.5 ± 1.6 (2.1–2.8)	2.4 ± 1.5 (2.1–2.7)	0.834	0.133	0.359	0.451
Stone size, mm	14.2 ± 7.1 (12.7–15.7)	14.1 ± 6.8 (12.7–15.5)	0.056	0.004	0.007	0.005
Total volume, mm³	409.5 ± 495.0 (303.3–515.6)	425.0 ± 492.9 (324.5–525.4)	0.310	0.602	0.211	0.144
Density, HU	978.4 ± 333.1 (907.0–1049.8)	1008.3 ± 338.6 (939.4–1077.3)	0.543	0.181	0.967	0.018
Stone composition			0.956	0.491	0.220	0.506
Stone location			0.371	0.941	0.479	0.700
Inferior calix angle^o	51.7 ± 50.6 (40.8–62.5)	50.7 ± 48.6 (40.8–60.6)	0.475	0.662	0.200	0.539
Operative time, minutes	52.6 ± 27.4 (46.7–58.5)	54.1 ± 28.1 (48.4–59.8)	0.197	0.760	0.071	0.115
Laser time, minutes	10.3 ± 14.5 (7.2–13.4)	11.4 ± 15.2 (8.3–14.5)	0.055	0.389	0.859	0.106
Laser energy, KJ	4.3 ± 6.0 (3.0–5.6)	4.8 ± 6.4 (3.5–6.1)	0.031	0.279	0.301	0.050
Laser pulses, N	6821 ± 9690 (4731–8912)	7490 ± 10096 (5422–9558)	0.056	0.323	0.331	0.751

CI = confidence interval; SD = standard deviation.

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