Could the twinkling artifact be a parameter in predicting the success of SWL? A prospective study Predicting the success of SWL with the TA

doi:10.21203/rs.3.rs-2009337/v1

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Could the twinkling artifact be a parameter in predicting the success of SWL? A prospective study Predicting the success of SWL with the TA

https://doi.org/10.21203/rs.3.rs-2009337/v1

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Introduction:

It is important to determine the factors to predict success before the treatment decision in urolithiasis. In this study, we aimed to predict the success of shock wave lithotripsy (SWL) by comparing the twinkling artifact (TA) revealed through color doppler ultrasonography (CDUS) with the stone density in non-contrast computed tomography (NCCT).

Material and method:

Eighty patients who underwent SWL between January 2021 and January 2022 were included in the study. Patients with stones of 5–20 mm in the renal pelvis and proximal ureter at NCCT were included the study. Age, gender, stone size, hydronephrosis grade, body mass index (BMI), Hounsfield unit (HU) in NCCT, and TA grades in CDUS of the patients were recorded. The stone-free rate after SWL, additional treatments, overall success rates, and the association between TA and success rates were evaluated.

Results

The mean age was 47.41 ± 15.08 years. The mean BMI was 24.49 ± 3.67 kg/m². Twenty three (28.8%) patients were TA grade 0, 33 (41.2%) patients were grade 1, and 24 (30%) patients were grade 2. The mean HU of TA grades 0, 1, and 2 of stones were 628 ± 107, 864 ± 123, and 1166 ± 292, respectively. HU increased along with the increase in the TA grade of the stone (p < 0.01). The mean number of SWL sessions was 2.26 ± 0.75 in patients with TA grade 0, and 2.92 ± 0.40 in patients with TA grade 2. The mean number of SWL sessions increased along with the increase in TA grade (p < 0.01). Stone-free rate following SWL decreased as TA grade increased. Stone diameter and TA were the only predictors of SWL success.

Conclusion

SWL is an important treatment option in the treatment of urolithiasis. We think that TA may be useful in predicting SWL success.

Twinkling artifact

Kidney stone

Shock wave lithotripsy

Color doppler ultrasonography

Urolithiasis is a common systemic disease all over the world. According to the European Association of Urology (EAU) guidelines shock wave lithotripsy (SWL), ureterorenoscopic lithotripsy, retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PCNL) were the treatment options for stones of different localization and size. [1]. SWL is a minimally-invasive treatment as the first choice, especially for stones less than 2 cm however, it has limitations that affect the success rate. One of these limitations is the degree of hardness depending on the chemical structure of the stone. Although there is not any precise imaging method that shows the hardness of the stone, the most widely used imaging method is the Hounsfield unit (HU) score in non-contrast computed tomography (NCCT) [2]. Furthermore, recent studies have shown an association between Twinkling Artifact (TA), which is a sonographic finding, and the chemical composition of the stone and the stone size [3]. The TA (also known as the twinkling sign, twinkle artifact, color comet-tail artifact, or Doppler twinkling) has been described first by Rahmouni et al. [4] to diagnose kidney stones. It is red and blue pixel combinations that rapidly change behind a strong reflecting object (i.e. kidney stone), which is like a turbulent blood flow. This phenomenon is thought to be secondary to intrinsic machine ‘noise’ within the color Doppler circuitry of the ultrasound device [5]. There is a limited number of studies showing that TA is one of the factors predicting the fragility of stones and the success of SWL [6, 7]. In this study, we aimed to show the effect of TA in predicting SWL success by comparing it with HU.

Following the ethics committee approval, 80 patients who have undergone SWL due to kidney stones in the urology clinic of our tertiary referral center between January 2021 and January 2022 were included in the study. The patients with stones in the renal pelvis and proximal ureter with a diameter between 5 and 20 mm detected by NCCT who have accepted to have SWL and consented were included in the study. Patients with body mass index (BMI) over 30 kg/m², patients with congenital renal anomalies, and those who had open stone surgery were excluded from the study. The urinary tract infection was evaluated with urine culture before SWL for all patients, in case of bacterial growth, adequate antibiotic treatment was prescribed. SWL treatment was performed after urine culture sterility. Age, gender, stone size, hydronephrosis grade, body mass index, HU, and TA of stones were recorded. The stone size was calculated by multiplying the largest axis diameters of the stone that cuts each other perpendicularly (mm²)[8].

NCCT imaging parameters were 120 kV, 300 mA, with a slice thickness of 5 mm and reformatting thickness of 1.25. The mean density of the stones was measured as HU in the ROI (Region of Interest) which covers the entire area of the stone in the tomography section in the abdominal window (WC:40, WW:400) where the kidney stone shows the largest area on the axial plane. TA was assessed by CDUS (Logiq 5, GE Medical Systems, Milwaukee, USA). A 3.5 MHz convex probe was used during the examination. Since ultrasonography is an individual decision-dependent imaging technique, patients were evaluated by two experienced radiologists. The absence of a TA signal was considered as grade 0, grade 1 was defined as the presence of the artifact but with partial acoustic shadowing, and grade 2 was considered as the presence of the artifact covering the whole acoustic shadowing.

The SWL procedure was performed by using the Elmed COMPLIT® lithotripsy (ELMED Medical Systems, Ankara, Turkey) device. SWL was performed in up to 3 sessions. The number of shocks was 1500–2500, the shock intensity was 14–22 kV with a frequency of 90 shock waves per minute for each session. The treatment was planned to be at least 7 days between two sessions. Analgesia was provided through intramuscular injection of diclofenac sodium of 75 mg to patients who had pain during SWL. The stone-free status following SWL was assessed by NCCT in the first month. The presence of a stone at and over 4 mm was considered a residual stone, and smaller stones were considered clinically insignificant residual (CIRF) stones. The overall success rate was assessed after all the additional treatments. The success rate after SWL, additional treatments, overall success rates, and the association between TA and success rates were evaluated prospectively.

Statistical Package for Social Sciences (SPSS) for Windows 22.0 (SPSS Inc, Chicago, IL, USA) program was used for statistical analysis. The Kolmogorov-Smirnov/Shapiro-Wilks test was used to test if the data present normal distribution. The number, percentage, mean, and standard deviation expressions were used for descriptive statistics. The chi-square /Fisher’s exact test was used to compare the categorized data. The Chi-square/Fisher exact test, Student's t-test, and Mann Whitney-U tests were used for the analysis of univariate analyses. Any p-value below 0.05 was accepted as statistically significant.

Eighty patients included in the study consisted of 54 (67.5%) males and 26 (32.5%) females. The mean age was 47.41 ± 15.08 years. The mean BMI was 24.49 ± 3.67 kg /m². The mean stone size was 79.51 ± 33.4 mm² (Table 1). The stone density was 887.01 ± 278.55 HU overall. The mean number of SWL sessions was 2.414 ± 0.79. No residual fragment was observed in 28 patients after SWL however, clinically insignificant residual fragments (CIRF, <4mm) were observed in 7 patients. Residual fragments were detected in 45 patients. The mean residual stone size was detected as 4.61 ± 5.16 mm. Semi-rigid URS was performed on 15 patients, RIRS was performed on 10 patients, and micro-PNL was performed on 4 patients for residual stone treatment. Overall stone-free status was observed in 64 patients (80%) after the additional procedures however, the residual fragment was observed in 16 patients (20%) (Table 2). There were no complications reported.

The TA grades of the patients were grade 0 in 23 (28.8%) patients, grade 1 in 33 (41.2%) patients, and grade 2 in 24 (30%) patients. The mean HU of TA grade 0, 1, and 2 stones were 628 ± 107, 864 ± 123, and 1166 ± 292, respectively. It was detected that HU significantly increased along with the increase of TA grade (p < 0.01) (Fig. 1). The mean number of SWL sessions was 2.26 ± 0.75 with grade 0 TA, and 2.92 ± 0.40 with grade 2 TA. It was detected that the average number of SWL sessions increased along with the increase in TA grade (p < 0.01). The stone-free rate following SWL decreased as TA grade increased (p = 0.001). The residual fragments were observed in 2 cases with TA grade 0 stones, and 5 cases with TA grade 1 stones. Residual fragments were observed in 9 cases with TA grade 2 stones. There was not any statistically significant difference between TA and overall stone-free status (p = 0.829) (Table 3).

Factors affecting the SWL success were also analyzed. In the univariate analysis stone largest diameter (mm), stone size (mm²), TA, and HU had a significant effect on the SWL success. In the multivariate analysis, three significant factors of univariate analysis (either stone largest diameter or stone size) were included. Stone's largest diameter and TA were the only predictors for SWL success (Table 4) (Fig. 1).

SWL is considered an important treatment option because of its high success rates and minimally invasive method when compared to other methods in the treatment of urolithiasis. However, many studies have shown that PCNL and URS have a higher stone-free rate than SWL [9]. There are some limitations to the success rate of SWL such as stone characteristics (size, location, composition, number), lithotripter type, and kidney anatomy. Therefore, it is important to identify potential predictors of SWL outcomes and define the ideal treatment option for each patient. Stone fragility is one of these parameters. The most important factor determining the stone's fragility is its composition [10]. Stone analysis is an important step in deciding the type of treatment. However, it is not possible to make a stone analysis without the stone fragments. Therefore, methods predicting the SWL success are essentially important. Although methods such as the degree of opacification of the stone on direct X-ray and molecular concentration measurements in serum and urine are used, there is not an ideal marker. For this purpose, correlations between radiological properties and compositions of stones were tried to be established in the literature to estimate the effectiveness of lithotripsy before the procedure. The NCCT was frequently used for this purpose and HU was specially assessed. NCCT enables to measure the density of the stone by HU to predict its hardness. Patel et al. [11] reported a significant difference between the mean HU values of calcium oxalate, uric acid, and struvite stones in their in vivo studies. Nakada et al. [12] reported no significant difference between the mean HU values of calcium oxalate, uric acid, and struvite stones different from Patel et al. Especially kidney stones over 5 mm are observed with echogenic focal lesion and distal acoustic shadowing in US device. Recent studies found a strong association between the size and density of a stone detected in NCCT, and the presence/absence of posterior acoustic shadow detected by US [13, 14]. There are also studies reporting that there is a close association between TA and posterior acoustic shadowing, and TA has a better diagnostic value in kidney stones [15]. In this study, we found that there is a positive correlation between HU and TA that was used to predict treatment in patients who underwent SWL. In addition, the success rate of SWL decreased with an increase in TA grade in the study.

The HU value of the stone calculated by NCCT is an important factor in predicting the fragility of the stone before SWL. Stones with more than 1000 HU are more resistant to SWL. [16]. Alan et al. [6] did not detect any significant association when they compared the TA and HU values of urinary stones in their study. Hassani et al. [17] have not found any significant correlation between the TA grades of calcium-containing and non-calcium-containing stones in the in vitro study. It is revealed in the present study that there is a positive correlation between HU which indicates the hardness of the stone, and TA. It should be noted that the differences in HU value may be due to the way of measuring the CT attenuation value of the urinary stone or the difference in the CT acquisition protocol. In the present study, the TA grade 0 stones presented lower HU, the success rate was higher after SWL. The success rate after SWL decreases along with the grade increase of TA. In the multivariate analysis of our study, while HU was not found to be an independent predictor, TA was found to be an independent predictor of SWL success. El-Nahas et al. [16] revealed that one of the factors predicting SWL success was HU. Similarly, in our study, a positive correlation was found between TA and HU in univariate analysis. However, in multivariate analysis, we found that the HU value was not as effective as TA in predicting SWL success. In our opinion, this shows that TA can be as effective as HU which is effective many times in the literature, in predicting the success of SWL. We think that the correlation between TA and HU and its effect on predicting SWL success can be revealed in future studies with a large number of patients.

Many studies investigated the association between the composition of urinary system stones and TA however, controversial results have been reported. Chelfouh et al. [7] found in their first in-vitro study that TA was frequently observed in calcium oxalate dihydrate and calcium phosphate stones, but it was rarely observed in calcium oxalate monohydrate and urate stones. Lee et al. [18] and Louvet [19] could not detect any correlation between TA and stone composition. Furthermore, Moore et al.[20] found in their in vitro study that all oxalate dihydrate and phosphoric acid stones had TA, some oxalate monohydrate and urate stones could have TA, while some stones did not have significant TA. Hassani et al. [17] found that TA could differentiate between calcium oxalate monohydrate and calcium oxalate dihydrate stones however, it could not differentiate between calcium and non-calcium stones, calcium oxalate, and calcium phosphate stones, or uric acid and cystine stones. Alan et al. [6] reported that TA was detected in almost all of the calcium oxalate dihydrate and calcium phosphate stones, and more than half of the calcium oxalate monohydrate and uric acid stones. Imamoglu et al. [21] detected in their study that Grade 0 and 1 stones are mostly composed of uric acid stones, and Grade 2 stones are mostly composed of cystine stones and calcium oxalate monohydrate stones which are hard. Hassani et al. [17] also reported a correlation between TA grade 2 and cystine stones. In our study, we could not include any stone analysis however, according to our findings it can be said that the hardness of the stone increases as the TA grade increases since the increase in TA grade is associated with lower SWL success and higher HU.

There may be many causes why such different results have been revealed in many studies in the literature. The mixed structure of the stones and radiologist-dependent detection of the TA may be among these reasons. Furthermore, it is seen that there are differences in the grading system and studies. It is also detected that some of the studies are in-vivo and some are in-vitro. [3, 7, 11, 17]. We believe that the reason for failure to achieve homogenization is the fact that the sources, sizes, and surface morphologies of the stones are different [3–6]. Therefore, we planned to investigate the effect of TA in predicting SWL success rates by minimizing other reasons that would affect success rates rather than stone analysis in the design of our study. We would also like to point out that TA may also be observed for reasons such as parenchymal and tumoral calcifications, and incrustation in ureteral double J catheters [22]. In the present study, the evaluation of stones observed in NCCT in terms of CDUS and TA is important to exclude other pathologies. Furthermore, we believe that the similar number of patients in the TA grade groups included in our study is important in terms of the homogenization of the study.

According to these findings, lower HU, grade 0–1 TA are associated with low-density stones. SWL should be considered primarily due to sensitivity. Stones with higher HU and Grade 2 TA suggest harder stones that may predict cystine and calcium oxalate monohydrate stones, and SWL success rates are lower. However, it should be noted that some of these may be mixed stones. In line with these results, we detected a significant increase in the number of sessions of SWL along with a grade increase in TA. Therefore, it would be more appropriate to consider a surgical method other than SWL in stones with higher grade TA.

One of the limitations of our study is the lack of analysis for stone composition although stones were evaluated with HU and TA. The limited number of patients was another limitation of our study. It might be due to the strict inclusion criteria of this study. However, this study might be one of the important studies evaluating the relationship between TA and SWL.

Shockwave lithotripsy is an important treatment option for urolithiasis. We think that TA can be useful to predict the fragility of stones when applying SWL. Prospective studies with larger patient series are needed to clarify the factors affecting the success and to reveal the association with TA while determining treatment methods.

Contributions of the authors to the article

M.S. and O.A. set up the main idea and hypothesis of the study. O.A., M.S., H.O.K., M.K. and B.A. developed the theory and edited the material method section. M.S., O.A., I.G.K., M.K. and O.Y.S. made the evaluation of the data in the results section. The discussion part of the article was written by M.S., O.A. and H.O.K.. O.A.. H.O.K., B.A., M.K., and I.G.K. have reviewed and made the necessary corrections and approved. In addition, all authors discussed the entire study and approved its final version.

Ethics committee approval: The study was approved by Kutahya Health Sciences University Ethics Committee on 30.09.2020 with the 2020-05/04 decision number.

Funding: No funding to declare.

Competing Interests: The authors declare no competing interests.

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Table 1. Patient's and stone's characteristics

(n=80 )

Age (years) (Mean±SD)

47.41±15.08

Gender (n) (%)

Male

Female

54 (67.5)

26 (32.5)

Side (n) (%)

Right

Left

39 (48.8)

41 (51.2)

BMI (kg/m²) (Mean±SD)

24.49±3.67

Stone size (mm²) (Mean±SD)

79.51±33.4

Number of stones (n) (%)

Single

Multiple

75 (93.8)

5 (6.2)

Number of Stones (mean±SD)

1.11±0.5

Stone localization (n) (%)

Renal pelvis

Proximal ureter

51 (63.75)

29 (36.25)

Grade of hydronephrosis (n) (%)

Grade-1

Grade-2

Grade-3

45 (56.2)

28 (35)

6 (7.5)

1 (1.2)

n: Number, BMI: Body mass index

Table 2. TA grades, HU scores, and post-treatment results of stones

	n=80
Stone-free rate (n) (%)	35 (43.8)
Residual stone size (mm) (mean±SD)	4.61±5.16
Auxillary procedure (n) (%) Semi-rigit URS RIRS PNL	15 (18.75) 10 (12.5) 4 (5)
Overall stone-free rate (n) (%)	64 (80)
Stone Hounsfield Unit (mean±SD)	887.01±278.55
Twinkling grade Grade 0 Grade 1 Grade 2	23 (28.8) 33 (41.2) 24 (30)

n: Number, URS: Ureteroscopy, RIRS: Retrograde intrarenal surgery, PNL: Percutaneous nephrolithotomy

Table 3. Comparison of TA grade with HU and the effect of TA grade on the number of SWL sessions and success rates

(n=80 )

p value

Mean Hounsfield Unit (±SD)

Twinkling Grade 0

Twinkling Grade 1

Twinkling Grade 2

628±107

864±123

1166±292

<0.001*

Mean ESWL session (±SD)

Twinkling Grade 0

Twinkling Grade 1

Twinkling Grade 2

2.26±0.75

2.15±0.87

2.92±0.40

<0.001*

Stone-free rate (n) (%)

Twinkling Grade 0

Twinkling Grade 1

Twinkling Grade 2

17 (73.9)

12 (36.4)

6 (25.0)

0.001*

Overall stone-free rate (n) (%)

Twinkling Grade 0

Twinkling Grade 1

Twinkling Grade 2

2 (12.5)

5 (31.25)

9 (56.25)

p=0.829*

* One way Anova, n: Number

Table 4. Factors affecting SWL success-Logistic regression analysis

	Univariate Analysis			Multivariate Analysis
	OR	95% C.I.	P value	OR	95% C.I.	P value
Gender	0.44	0.165-1.195	0.108
Age	0.99	0.962-1.021	0.544
BMI	0.94	0.829-1.062	0.316
Stone localization	1.28	0.992-1.648	0.057
Stones’ largest diameter (mm)	0.76	0.627-0.913	*0.004*	0.78	0.636-0.960	*0.019*
Stone size (mm²)	0.98	0.969-0.998	*0.030*
Stone number	0.38	0.068-2.149	0.276
Twinkling Artifact Grade	0.34	0.174-0.657	*0.001*	0.39	0.194-0.781	*0.008*
Hounsfield Unit	0.99	0.995-0.999	*0.006*
Stone-skin diameter	0.91	0.755-1.088	0.290

No competing interests reported.

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Could the twinkling artifact be a parameter in predicting the success of SWL? A prospective study Predicting the success of SWL with the TA

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Abstract

Introduction:

Material and method:

Results

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Introduction

Material And Method

Results

Discussion

Conclusion

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