a b s t r a c t

Background/Aim: Computed tomography (CT) is generally used for Ureteral stone diagnosis. Unnecessary imaging use should be reduced to prevent increased radiation exposure and lower costs. For this reason, scoring systems that evaluate the risk of ureteral stones have been developed. In this study, we aimed to investigate the diagnostic accuracy of the modified STONE score (MSS) and its ability to predict ureteral stones.

Materials and methods: The research was conducted as a multi-center, prospective and observational study. Pa- tients aged 18 and over who presented to EDs with complaints of flank pain and who received a CT were in- cluded. Patients were divided into two groups based on the presence or absence of stones, and the categories of the MSS were determined. The ability of the MSS to predict the ureteral stone and its diagnostic accuracy were calculated.

Results: The median age (min/max) of the 367 study patients was 37 (18/91), and 244 (66.5%) were male. A ureteral stone was present in 228 (73.0%) patients. Male gender, previous stone history, duration of pain less than 6 h, presence of hematuria, and CRP value below 0.5 mg/dL were significantly more com- mon in the group with stones. The prevalence of ureter stones in the MSS high-risk group was 96.0%. The area under the receiver operating characteristic curve and sensitivity of the MSS was 0.903 and 0.81, respectively.

Conclusion: The modified STONE score has high diagnostic performance in suspected urinary stone cases. This scoring system can assist clinicians with radiation reducing decision-making.

(C) 2021

1. Introduction

Ureteral stone is a common urological disease in the emergency de- partment (ED) and it’s responsible for over 1 million ED visits in the United States (USA) every year [1]. The overall prevalence of the ure- teral stone disease in Turkey is about 14% [2].

Computed Tomography (CT) is the first preferred imaging method in patients with suspected ureteral stones in the USA and European countries [3]. Although CT scans have increased the detection rates of ureteral stones and other important Alternative diagnoses, it has been questioned in terms of cost-effectiveness and radiation exposure [4]. For this reason, various scoring systems have been developed to evalu- ate the risk of ureteral stones in order to prevent the use of unnecessary imaging and to reduce radiation exposure in patients presenting with

* Corresponding author at: Specialist of Emergency Medicine, Beylikduzu State Hospital, Emergency Department, Pinartepe Mahallesi, 34500, Buyukcekmece/Istanbul, Turkey.

E-mail address: [email protected] (S. Bahadirli).

flank pain. One of these is the STONE score, which was published and developed in 2014 by Moore et al. [5]. Another one is the Modified STONE score (MSS), which was derived from the STONE score in 2016 by Kim et al. [1].

Although there are many studies about the STONE score in the liter- ature, there are few studies that address or evaluate the MSS. This study was conducted to investigate the diagnostic accuracy of the MSS and its ability to predict ureteral stones in the Turkish population.

1. Materials and methods
   1. Study design

The research was conducted as a multicenter, prospective and obser- vational. Three hospital located in different geographical regions of Turkey were included as study sites. The institutional review board ap- proved the study and issued a waiver of consent (approval date/num- ber: 26.04.2017/130). The study was conducted in compliance with the ethical principles of the Helsinki Declaration.

https://doi.org/10.1016/j.ajem.2021.03.073

0735-6757/(C) 2021

• 1. Selection of patients

Between April 15, 2017 and October 15, 2017; adult patients 18 years and older presenting to the EDs with a primary complaint of unilateral or bilateral flank pain were enrolled in the study. The physician who examined the patient decided whether the patient should undergo a CT scan based on his/her own clinical assessment. Eligible patients had a final clinical diagnosis combined with a CT scan. As the definitive diag- nosis was confirmed with CT, patients without CT scan were excluded. Other exclusion criteria were: history of trauma, known active malig- nancy, known kidney disease (including creatinine>1.5 mg/dL), pres- ence of leukocytes in Urine microscopy, objective fever (> 37.7 ?C), and missing laboratory data. The patients included in the study were divided into two groups, those with and without ureteral stones (Fig. 1).

• 1. Modified STONE score

In the MSS system, patients are scored based on gender, duration of pain, presence of hematuria, previous stone history and CRP value (Table 1). The patients were categorized into three groups according to MSS as low (0-4 points), medium (5-9 points), and high-risk (10-16 points). The prevalence of ureteral stones and important alter- native diagnoses such as acute appendicitis, cholelithiasis, newly de- tected malignancy, acute cholecystitis, acute pyelonephritis, ovarian

Table 1

Scoring chart of modified STONE score.

Variables Points

Male gender 3

Duration of pain <6 h 3

Hematuria 6

Previous stone history 2

CRP <5 mg/dl 2

Total 0-16

cyst, etc. were determined for each group. In the original study, it was determined that the patients in the high-risk group (MSS >= 10) were positive for ureteral stones and the other 2 groups were negative, the sensitivity of the MSS was 0.80, and the specificity was 0.99 [1].

• 1. Data collection

A standard study form was prepared in order to record the data of the patients included in the study. The form includes demographics (age, gender), self-reported medical history (duration of pain, previous stone history, nausea, vomiting, etc.), results of laboratory tests (blood and urine) and CT scans. This form was filled out by the emergency phy- sician on-duty. The MSS of the patients were calculated using the data in

496 Flank pain with CT Scan

24 Trauma

14 Malignancy

23 Renal Disease (Cr>1.5 mg/dL)

19 Piyuria

1197 Flank pain

701 w/o CT Scan

367 Inclusion

268 (73.0%)

Stone

99 (27.0%)

Other dx

61 (16.6%) Insignificant findings

38 (10.4%) Significant findings

Fig. 1. Flowchart of the enrolled patients.

the standard study form. In light of analyzes and evaluations, the diag- nostic and predictive accuracy of the MSS was investigated.

2.5. Statistical analysis

Categorical data were presented as frequency and percentage. The frequencies of categorical variables were compared using the chi- square and Fisher’s exact test as appropriate. Continuous variables were tested for distribution using the Kolmogorov-Smirnov test. The asymmetrically distributed variables were analyzed with the Mann- Whitney U test and are expressed as the median (min-max). The prev- alence of ureteral stones and important alternative diagnoses were de- termined for each group. The effectiveness of the modified STONE scoring system to predict Urinary stones was examined with the re- ceiver operating characteristic (ROC) curve. A 2-sided P-value 0.05 was regarded as statistically significant. All data analyses were per- formed using SPSS version 22.0 software (SPSS Inc., Chicago, IL, USA).

Table 3

Types and frequency of important alternative diagnoses by modified STONE score

categories.
Important Alternative	Low-risk	Moderate-risk	High-risk	Total
Diagnoses	(n = 21)	(n = 14)	(n = 3)	(n = 38)
Acute Appendicitis	4	3	-	7
Cholelithiasis	2	2	1	5
Newly Detected	2	1	1	4
Malignancy Acute Pyelonephritis	2	1	-	3
Acute Cholecystitis	1	2	-	3
Ovarian Cyst	1	1	1	3
Enterocolitis	1	1	-	2
inguinal hernia	1	1	-	2
Ureteropelvic Stenosis	1	1	-	2
Renal infarction	1	-	-	1
Ovarian Cyst Rupture	1	-	-	1
Pelvic Inflammatory	1	-	-	1

Disease

Peptic ulcer perforation 1 - - 1

Endometriosis 1 - - 1

1. Results

Thoracolumbar Spondylosis

1 - - 1

Of the 1197 of ED patients presenting with flank pain complaints, 367 met the inclusion criteria (Fig. 1). The median (min/max) age was 37 (18/91) and 244 (66.5%) of them were male. The duration of pain was less than 6 h in 53.1% of the patients, and 50.4% had accompanying nausea and/or vomiting. 42.0% of the patients had a previous stone his- tory and the most common laboratory abnormality was hematuria with 70.6%. According to CT scan results, 268 (73.0%) patients had ureteral stones. The comparison of the baseline data and the MSS between pa- tient groups were shown in Table 2. Imaging results were completely normal in 61 (16.6%) of 99 (27.0%) patients without stones (Fig. 1). However, important alternative diagnoses other than ureteral stones in- cluding acute appendicitis, cholelithiasis, newly detected malignancy, acute cholecystitis, acute pyelonephritis, ovarian cyst etc. were detected in 38 (10.4%) of the patients without stones (Fig. 1). Types and fre- quency of important alternative diagnoses by modified STONE score categories were shown in Table 3.

According to the MSS calculations, 50 (13.6%) of the patients were in the low, 90 (24.5%) were in the moderate, and 227 (61.9%) were in the high-risk group. The prevalence of ureteral stones was 96.0% (218/227) in the high-risk group, 52.2% (47/90) in the moderate, and 6.0% (3/50) in the low-risk group. On the other hand, as the score decreased from the high to moderate and low-risk groups, the prevalence of important alternative diagnosis increased. The rates were 1.3% (3/227), 15.6% (14/90) and 42.0% (21/50), respectively. The prevalence of ureteral stone and important alternative diagnoses by the MSS categories were shown in Fig. 2.

Acute Pancreatitis - 1 - 1

Male gender, previous stone history, duration of pain less than 6 h, presence of hematuria and CRP value below 0.5 mg/dL were signifi- cantly more common in the group with stones (p < 0.001) (Table 2). There was also a significant difference between patients with and with- out stones in terms of MSS median (min/max) values [13 (1/16), 5 (0/16), respectively; (p < 0.001)] (Table 2). There was no significant difference between the groups in variables of age, nausea and/or vomiting, leukocyte count (<12.000 cells/mL), BUN (<26 mg/dL) value and creatinine (<1.2 mg/dL) value (p > 0.05) (Table 2).

We determined the optimum cut-off value for the MSS to be 10, with

0.81 sensitivity and 0.89 specificity. Accordingly, the MSS high-risk group was considered positive for ureter stones and the other two groups were negative. The ROC analysis was performed to assess the ability of the MSS to predict ureteral stones, and the area under the curve (AUC) was 0.906 +- 0.019 (95% CI, 0.869-0.943; p < 0.001)

(Fig. 3).

1. Discussion

In this study, we investigate the utility, sufficiency, and Predictive ability of the MSS as applied to patients who visited three EDs in Turkey with flank pain complaints. In our sample, the MSS high-risk

Table 2

The comparison of the baseline data and modified STONE score between patient groups.

Variables	Total (n = 367)		Ureter Stone (n = 268)		Without Stone (n = 99)	p
	Median (Min/Max)		Median (Min/Max)		Median (Min/Max)
Age, years	37 (18/91)		37 (18/75)		38 (18/91)	0.757
Modified Stone Score	11 (0/16)		13 (1/16)		5 (0/16)	<0.001
	n (%)		n (%)		n (%)
Gender, male	244 (66.5)		202 (75.4)		42 (42.4)	<0.001
Previous stone history	154 (42.0)		140 (52.2)		14 (14.1)	<0.001
Duration of pain, <6 h	195 (53.1)		176 (65.7)		19 (19.2)	<0.001
Nausea and/or vomiting	185 (50.4)		143 (53.4)		42 (42.4)	0.077
WBC, <12.000 cells/mL	272 (74.1)		203 (75.7)		69 (69.7)	0.283
Hematuria	259 (70.6)		234 (87.3)		25 (25.3)	<0.001
Creatinine, <1.2 mg/dL	297 (80.9)		213 (79.5)		84 (84.8)	0.295
BUN, <26 mg/dL	326 (88.8)		236 (88.1)		90 (90.9)	0.466
CRP, <5 mg/dL	293 (79.8)		232 (86.6)		61 (61.6)	<0.001
Modified Stone Score >= 10	227 (61.9)		218 (81.3)		9 (9.1)	<0.001

Mann Whitney U test, Pearson Chi-Square Test, Fisher Exact Test, Min.:Minimum, Max.:Maximum, WBC: White blood cells, BUN: Blood urea nitrogen, CRP: C-reactive protein. Important p values and related variables are shown in bold.

Fig. 2. Prevalence of ureteral stone and important alternative diagnoses by modified STONE score categories of low, moderate and high-risk (a); MSS-negative and MSS- positive (b).

group was very sensitive in detecting ureteral stones with a ratio of 96.0%. The overall prevalence of ureter stones in our study population was 73%. In the original research of MSS, which was conducted as a ret- rospective, single-center study with 700 patients in Korea, the prevalance of ureter stones was 79% [1]. In recent investigations con- ducted in the Turkish population, these rates were between 49% to 84% [6-8].

The 41% of patients who presented to the ED with flank pain re- ceived a CT scan. In studies conducted in different countries, this rate varies between 52.8% and 77.0% [1,9,10]. We did not use any protocols that mandate a CT scan during our study. Patients with provided pain control and no abnormal laboratory results were discharged without imaging or using alternative imaging methods according to the physician’s gestalt. The lower CT scan rates can be explained by these.

Fig. 3. ROC curve of MSS (>=10) at diagnosis of ureteral stone^JPY. ^JPYSpecificity 0.89, Sensitivity 0.81; AUC 0.906 +- 0,019 (%95 CI, 0.869-0.943), (p < 0.001).

The rate of detecting important alternative diagnoses was 10% in our study sample which compares with the lower end findings of sim- ilar studies (10% - 22.1%) [1,11,12]. The increased use of CT scans in other countries when evaluating flank pain likely explains the higher detection rates of incidental diagnoses when compared to EDs in Turkey.

Our results showed that; male gender, duration of pain less than 6 h, previous stone history, presence of hematuria on urine microscopy, and C-reactive protein (CRP) less than 0.5 mg/dL were predictive factors for ureteral stones; and these parameters were the same as those deter- mined in the original study and the study of Acar’s [1,7].

We determined the optimum cut-off value for the MSS to be 10, as in the original study. This cut-off value divides the patients into MSS- positive and MSS-negative groups. The MSS-positive group corre- sponds to the MSS high-risk group at this cut-off value, as both include patients with a modified STONE score of 10 or more. The prevelance of ureteral stones in MSS-positive group was 96.0% in our study, and it was 98.0% in the original MSS study [1]. Similar results in predicting ureteral stones were seen when comparing the AUC values of our study (0.91 95% CI, 0.87-0.95, p < 0.001) to those of the original study (0.94 95% CI, 0.91-0.97, p < 0.001). In the same order, the sen- sitivity was 0.81-0.80 and specificity was 0.89-0.99. A recent retro- spective study of 157 patients in Turkey by Acar, compared three scores, including MSS. They found the prevalence of ureteral stones 88.9%, the sensitivity 0.88, specificity 0.71 and the AUC value 0.82 (95% CI, 0.75-0.90; p < 0.001) for the MSS-positive group [7]. Our re- sults were slightly better than Acar’s study. The cut-off value differ- ences, which was 7 in the study of Acar and 10 in our study, were thought to affect these results.

Important alternative diagnoses other than ureteral stones were found in 3 (1.3%) patients in the MSS-positive group. These diagnoses were ovarian cyst, cholelithiasis, and a newly detected mass in the kid- ney (Renal cell carcinoma). The rate of important alternative diagnosis in the MSS-positive group was 1.9% in the original MSS study and 1.6% in the original STONE study [1,5]. On the other hand, the important al- ternative diagnosis rate in MSS-negative group was 25.0% (35/140) in our study (Fig. 2b) and 23.5% (38/162) in the study of Kim et al. For this reason, advanced imaging may be considered necessary for patients in the MSS-negative group.

Flank pain complaints are often recurrent and these patients, mostly young, frequently visit the EDs. The literature shows that exposure to cumulative radiation increases the risk of cancer; and especially young patients are at higher risk than the elderly [4,13]. In addition, unneces- sary CT scans increase costs and the duration of hospitalization. Since MSS positivity is highly predictive of ureter stones, it may be relied upon to support the decision to use lower risk Confirmatory imaging studies such as ultrasound, or to forego additional imaging altogether. In our study, 59.4% (218/367) of patients with a positive MSS had ureteral stones; and this ratio was 64.2% in the study of Kim et al. This can be interpreted that the MSS can reduce the use of CT by approximately 60%.

• 1. Limitations

There are a few limitations in our study. Ureteral stone disease prev- alence is quite common in Turkey. It may differ from country to country due to differences such as geographical conditions, lifestyle and eating and drinking habits. The results of this study, which we conducted only on the Turkish population, should be supported by studies includ- ing different countries. The physician gestalt, also known as the general clinician estimation after initial evaluation, was not assessed in our study. In accordance with the MSS procedure, we included patients whose ureteral stone diagnosis was confirmed by CT only. USG is also widely used in ureteral stone diagnosis in our country. These reasons led to a decrease in our sample size.

1. Conclusion

In this external validation study, we found that the MSS was signifi- cantly successful in predicting and diagnosing ureteral stones, as in the original study. This scoring system can assist clinicians with decision- making that reduces radiation exposure to patients. Given the new scores developed, these results should be supported by studies with broader participation in different countries.

Meetings

This article has not been presented in any scientific meetings. We don’t have any manuscript already published from the study.

Data availability

The authors agree to the conditions of publication including the availability of data and materials in our manuscript.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Informed consent

The need for informed consent was waived.

Ethical approval

This study was approved by the local ethics committee (Istanbul Medipol University Non-Interventional Clinical Research Ethics Com- mittee. Decision date and number: 26.04.2017/130).

Human rights

The principles outlined in the Declaration of Helsinki have been followed.

Declaration of Competing Interest

Authors declare that they have no conflicts of interest.

Acknowledgements

None.

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