The stone density does not affect the stone-free rate of kidney pelvic stones (2-3 cm) treated with exible ureterorenoscopy

Objectives To compare the ecacy of retrograde exible ureterorenoscopy (FURS) in the treatment of low-density stone (LDS) and high-density stone (HDS). From January 2017 to March 2019, 241 patients with 2–3 cm kidney pelvic stones were treated with retrograde exible ureterorenoscopy. The relevant study parameter for all patients, including patients age, body mass index (BMI), gender, stone density values (Hounseld units [HU]), stone size, stone location, operative time, hospitalization time, stone free rate (SFR), complications were evaluated. The results were assessed one month after the FURS and the follow-up time is 6 months. 6 patients with elevated SCr elevation (>0.5 mg/dl), 3 patients with urinary tract infection 5 patients infections requiring additional antibiotics and 3 patients with ureteric calculus. All patients with fever, infection and elevated SCr are returned to normal after a few days, and no serious complications happened.


Background
Nephrolithiasis are common in all over the world and the prevalence and morbidity of this disease are increasing over the past decades [1]. A number of techniques have been described for the treatment of renal stones, including shock wave lithotripsy (SWL), retrograde exible ureterorenoscopy and percutaneous nephrolithotomy (PCNL) [2]- [5]. Such approaches have their own advantages and disadvantages; PCNL is recommended as the gold standard for renal calculi larger than 2.0cm, due to the higher stone-free rate [6] [7]. FURS is considered to be the perfect way to treat kidney stones due to its low invasiveness, small damage and high SFR. With the improvement of lithotripsy techniques (YAG laser), SFR was further enhanced [8]. But because of the stone density and the limitation of operating time, with one operation, we still can't crush all the stones. The cost of treating stone disease is expected to increase by $1.24 billion per year by 2030 due to population growth and the prevalence of kidney stones [1], [9].
How about the e cacy of FURS in the treatment of different density kidney pelvic stones? can we speculate something that is helpful to the patients through the stone density before the operation?
Non-contrast CT (NCCT) and kidney, ureter, and bladder (KUB) X-ray have become standard examinations for patients with kidney stones [10]- [13]. New ESWL performance predictors are identi ed with the data provided by the NCCT [14]. One study [15] showed that stones with a density of > 1000 HU are less likely to disintegrate. However, no published paper demonstrates the e cacy of FURS in the treatment of different density kidney pelvic stones (measured stone density by NCCT).
The purpose of this study is to compare the results of kidney pelvic stones between LDS group and HDS group that are treated with FURS.

Methods
Initially, from January 2017 to March 2019, 300 patients who received FURS in our organization were included in our study and 241 patients were included in the nal post-screening analysis shown in gure 1. Criteria for inclusion: age >18 years, unilateral kidney pelvic stone 2-3 cm, normal body mass index.
Exclusion criteria: no operative contraindications, moderate and severe hydronephrosis, renal anatomy abnormality.
Preoperative NCCT and KUB have been implemented for all patients. Patients' related statistical parameters, including age, BMI, gender, NCCT value (Houns eld units [HU]), size and location of the calculis were recorded. Preoperative routine laboratory tests, including serum creatinine, coagulation screen, sterile urine culture, have been completed previous to operation. If the culture of the urine is found to be positive before surgery, or if the blood test shows signs of infection, anti-infective treatment will be given, and surgery will be performed after infection control. The density of the stone is the average of three points measured at that location as shown in gure 2. Stone size was evaluated based on European Association of Urology guidelines [16]. Remaining fragments of stone <3 mm was considered freestone and successful treatment.

FURS technique
A normal FURS operation was carried out on all patients [17]. After general anesthesia in the lithotomy, a safety guide wire (Cook) is placed in the kidney. 9.5F semirigid ureteroscope (Germany) was performed to inspect the ureter and ureteropelvic junction in all patients. Ureteral access sheath was routinely inserted into the renal pelvis under the guidance of guide wire. FURS was performed using URF P-5 exible ureterorenoscopy (Olympus, Tokyo, Japan) and a 200μm YAG lasers. We used a holmium laser machine (Trimedyne, America) with an energy of 0.8 J and a rate of 25 Hz, with a total power of 20 Hz. When we disintegrate the stone at the beginning, we will disintegrate the stone slowly from the edge, instead of disintegrating it into a few smaller stones, then crushing it in pieces, because the stones are not easy to x when they are small, so it's very di cult to crush them later. In the end, a modi ed basket (Cook) was used to retrieve fragments larger than 3 mm. 6 F double-J (D-J) stents were placed in all patients and removed at the appropriate time. The operation was carried out by the same person, Professor Zhang.

Statistical analysis
The data is shown as a mean ± standard deviation (SD). The study data was analyzed using SPSS23.0.
Differences in categorical data between groups were tested using χ2. For the evaluation of continuous variables, the Student's t test was used, statistical signi cance was de ned as P < 0.05.

Results
The preoperative parameters of 241 patients were shown in Table 1. According to the density of the stones, we divide the patients into two groups, LDS group (HU<1000) and HDS group (HU≧1000), respectively. These two groups have similar basic parameters, including age, gender, BMI and stone size.
Following one month of operation, post-operative X-rays and kidney ultrasound were assessed for SFR, if they had no evidence of stones or residual fragments of less than 3 mm, the operation was considered to be a success. As is shown in table2, in all, 223 (92.5%) patients were stone-free and 18 (7%) had residual fragment after treatment with FURS at one month. These two groups have a similar SFR, HDS group (93.5%) and LDS group (91.5%), respectively.
Although operating time in the HDS group was signi cantly longer, they had similar hospitalization time and cost for the entire operation. The LDS group had a higher street stone formation than the HDS group. During the follow-up, we found that the LDS group had to keep the D-J stent longer, with an average time of 28 days. Of cause, this will increase the feeling of discomfort in the lower abdomen of these patients.
As shown in table 3, complications were assessed by the improved Clavien grading system as previous described [18].

Discussion
PCNL was considered to be the best way to tackle large renal stones, regardless of its success rate of operation or its higher SFR [19]- [21]. However, in a large number of recent studies, we have observed that severe complications following PCNL are being reported such as fever, sepsis, hemorrhage requiring blood transfusion and pneumothorax [22], [23] [24]. Lots of scholars reported that some patients are poor medical candidates for PCNL [25], [26]. They need to disintegrate the stone with the FURS. In my study, FURS was performed with 2-3 cm kidney pelvic stone and the results of this method were compared between the LDS group and the HDS group. The stone density measured by the NCCT and the patients were divided into two groups (LDS group: HU<1000, HDS group: HU≧1000) depending on the stone density. Our results showed that there was no signi cant difference between the two groups in terms of postoperative HB level, hospitalization time, stone-free rate and retreatment rate. However, the mean total operating time is apparently longer in the LDS group, and this group also has more ureteric calculus.
FURS has been gradually accepted by patients and doctors in the treatment of larger renal stones (≧2 cm) as it can achieve a satisfactory free stone rate but rarely complications [27]. Because of some patients who cannot tolerate PCNL, the introduction of a new generation of YAG laser or thulium ber laser and the development of endoscopic technology. FURS is the most attractive option for bigger kidney stones. The success rate for FURS may depend on many factors, such as the location of stone, size, density, years, gender, side and BMI. Pervious, One study showed that the total average operating time in the hard stones group was signi cantly longer [27]. However, in our study, the results were compared between the LDS group and the HDS group, showing that the total operating time in the LDS group is signi cantly longer. These two outcomes are the opposite. There may be a variety of reasons. First of all, the equipment used in each operating room is different. In this study, the latest Holmium laser and FURS were used to ensure the e ciency of the lithotripsy process. Secondly, the surgeon's experience is important as well. Unexperienced doctors break the stones rapidly into small pieces and crush them one after another ( Figure 3A). However, our approach is to break the stone slowly from the edge of the stone, just like peeling ( Figure 3B). Of course, when the stones get smaller, it's a bit di cult. Why does our result show that the LDS Group's operating time is signi cantly longer? Not hard stone is easily broken into a few large pieces in a short time, and then, due to its exible mobility, it is hard to keep breaking and take longer to remove fragments using a stone basket. Because of the compactness of the hard stone, as the ants eat, the surgeon can break the stone into small particles, and only little fragments need to be removed by a stone basket. That's why we're using a very short operating time in the HDS group.
Stone Street is a common complication for the three different ways (SWL, PCNL and FURS) to disintegrate the stone [7], [28]. Normally after dealing with laser, some large fragments still need to be removed by a stone basket but we cannot remove all of them, the remaining stones will be eliminate along the ureter, and of course, we will keep the D-J ureteral stent to minimize the formation of stone streets. One study showed that stone street occurs in approximately 15% of cases after ESWL [29]. The incidence of this phenomenon will be relatively lower following the operation of PCNL and FURS. In this study, we found that the stone street incidence of the LDS group (10%) was higher than the HDS group (2.4%). Because more smaller fragments are formed in the LDS group during the stone disintegrating process. In consistent with this, we found that we need to keep the D-J stent longer in the LDS group to make sure that the stone can be eliminated from the ureter (Group LDS vs Group HDS: 28 vs 21 days).
The limitation of this study is the less-sample nature of its design, a single-surgeon, a retrospective nature, and single-center design. CT value 1000HU is certainly an appropriate relative value that more is required to acquire a comparatively credible value through more clinical data.

Conclusion
FURS is safe and effective for the treatment of large kidney stones. It has been con rmed that the use of NCCT to measure renal stone density before FURS helps to predict the outcome of the treatment. FURS should be decided as a common approach in the treatment of kidney pelvic stones > 2 cm for preferred patients. Low-density stones need longer total operating time and result in more stone streets and need to keep D-J stent longer. All authors have read and approved the manuscript and ensure that this is the case.

Abbreviations
[28] Y. Kato, S. Yamaguchi, J. I. Hori, M. Okuyama, S. Kaneko, and S. Yachiku, "Utility of ureteral stent for stone street after extracorporeal shock wave lithotripsy," Acta Urologica Japonica, vol. 51, no.   Table 3 Classi cation of lower stone density group and higher stone density group complications according to the modi ed Clavien grading system  Stone location where the density was measured. Kidney pelvic stones labeled with a red arrow Stone disintegrating effect diagram Low-density stones crack into large pieces(A), but high-density stones crack into small particles(B).