ENDOUROLOGY AND STONE DISEASE The Feasibility, Safety, and Efficacy of the Preemptive Indwelling of Double-J Stents in Percutaneous Nephrolithotomy Surgery: A Randomized Controlled Trial Fuding Bai, Huifeng Wu, Nan Zhang, Jimin Chen, Jiaming Wen* Purpose: The goal of this study is to compare the feasibility, safety, and efficacy of the preemptive indwelling of double-J stents (PI-DJS) versus the conventional preemptive indwelling of ureteral catheters (PI-UC) in percuta- neous nephrolithotomy (PCNL) via a randomized, controlled clinical study. Materials and methods: A total of 75 patients with complex renal calculi underwent PCNL surgery and were randomized, using random number table, to receive either a PI-DJS (37 cases) or a PI-UC (38 cases). All operations were performed by the same experienced surgeon. Several outcomes were measured, including duration of opera- tion, time to establish passage, level of hemoglobin decline, rate of stone clearance and incidence of complications. Results: Guided by B-ultrasound, percutaneous passages were successfully established in all patients who then un- derwent one-stage PCNL. The time required to establish a passage using a PI-DJS was 7.5min, whereas that of the group who received a PI-UC was 11.5min (P < 0.01). There was no significant difference between the two groups in terms of operation duration, postoperative Hb decline rate, stone clearance rate, and perioperative complication incidences (all P > 0.05). Conclusion: PI-DJS during PCNL allowed for a reliable and stable reflux from the bladder into the renal pelvis to produce an artificial hydronephrosis without the formation of microbubbles, unlike conventional ureteral catheters. Keywords: percutaneous nephrolithotomies; randomized controlled study; indwelling of double-J stents; indwell- ing of ureteral catheters INTRODUCTION Ever since it was described by Fernstorm et al in 1976(1), percutaneous nephrolithotomy (PCNL) has become an important therapeutic strategy for the treat- ment of complex renal calculi(2), even in complicated situations like pregnancy(3,4). PCNL was demonstrated as an effective therapy to achieve stone-free rates in about 80% of patients with staghorn stones(5), one of the most challenging forms of urolithiasis. However, there are always challenges in the management of complex renal calculi during the PCNL process(6) and many im- provements have been described that significantly en- hance the safety and surgical outcome of PCNL(3,7-9). In order to have a successful PCNL, it is very essential to have an accurate puncture through the papilla into the target calyx, thereby creating the percutaneous access for stone disintegration and removal. In recent years, B-ultrasound localization for percutaneous renal punc- ture has seen higher adoption due to its enhanced accu- racy, reliability, and safety, which was routinely used for PCNL surgery(2). Importantly, percutaneous punc- ture often requires artificial hydronephrosis, which was traditionally achieved through perfusion of saline via a ureteral catheter. This method, however, might generate bubbles in the renal pelvis, leading to interference of B-ultrasound-guided percutaneous punctures(10). Addi- Department of Urology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou , China. *Correspondence: Department of Urology, Second Affiliated Hospital, School of Medicine, Zhejiang University , No. 88, Jiefang Road, Hangzhou, Zhejiang, China, 310009. Tel: +86-571-87783550, E-mail: wenjiaming@zju.edu.cn. Received November 2018 & Accepted May 2019 tionally, sometimes indwelling of the double J stents at the end of the surgery presents difficulties and the po- sitioning of the stent might be inaccurate. In this study, a randomized, controlled clinical trial was conducted to investigate the feasibility, safety, and efficacy of the preemptive indwelling of double-J stents (PI-DJS) be- fore PCNL, hoping to simplify the procedure in order to optimize surgical outcomes. MATERIALS AND METHODS Targeted patients and methods The present clinical trial is registered in the Chinese Clinical Trial Register (ChiCTR, 1900021443). From August 2014 to December 2016, 75 cases of patients with complex renal calculi were randomly assigned to two different groups to undergo PCNL operations. 37 out of 75 cases underwent the procedure entailing the PI-DJS, while the remaining 38 cases underwent the procedure involving the conventional preemptive in- dwelling of the ureteral catheter (PI-UC). All operations were performed by the same experienced surgeon. All patients underwent one-stage PCNL in which percuta- neous renal punctures were successfully established via B-ultrasound guidance. The general information of the two groups of patients is shown in Table 1. Urology Journal/Vol 17 No. 3/ May-June 2020/ pp. 232-236. [DOI: 10.22037/uj.v0i0.4957] Vol 17 No 03 May-June 2020 233 Inclusion and exclusion criteria Renal stones were diagnosed by either CT or kidney, ureter, and bladder (KUB) examinations. Patients (18- 80 years old) with stone sizes larger than 2cm that re- quired PCNL treatment were included in this study. The exclusion criteria include coagulation disorders, anatomic anomalies, urinary tuberculosis, previous PCNL history, and severe cardiac and pulmonary dys- functions. Total 92 patients were assessed for eligibility (Figure 1). Among them, 17 patients were excluded from the study due to not meeting inclusion criteria (n=9), de- clined to participate (n=6) and other reason (n=2). Preemptive indwelling of double-J stent group (PI-DJS) Under general anesthesia, patients were placed in the lithotomy position. The retrograde insertion of an Fr6 double-J stent via the ureter to the kidney was per- formed under transurethral ureteroscopy. Subsequently, a three-way Foley catheter was placed, and the urine drainage port was closed. Physiological saline (bag of 3000ml, height about 60 ~ 80cm) was connected to the irrigating cavity. With the patient in prone position, the cavity was in- fused with normal saline to produce artificial hydro- nephrosis depending on reflux from the bladder to the renal pelvis. The posterior renal calyx was punctured under the guidance of B-ultrasound. Guided by zebra guidewire, the percutaneous passage was expanded from F8 to F20 and a renal sheath was used for the en- trance of kidney calices. Subsequently, ureteroscopic lithotripsy was performed with a holmium laser under 8/9.8F ureteroscope. An F18 nephrostomy tube was retained subsequent to surgery. Plain film of kidneys, ureters and bladder (KUB) or B-ultrasound examination was performed 3-5 days after the operation to evaluate the presence of any residual stones. Stones larger than 5mm would be con- sidered incomplete removals. Conventional Pre-emptive indwelling of ureteral catheter (PI-UC) group Under general anesthesia, the patient was placed in the lithotomy position. Retrograde ureteral catheterization was performed under transurethral ureteroscopy and an F6 ureteral catheter was inserted into the kidney. After the patient was placed in the prone position, physiolog- ical saline was infused through the ureteral catheter to generate artificial hydronephrosis. The posterior renal calyx was punctured under the guidance of B-ultra- sound technology. After the stone fragments were removed, the ureteral catheter was removed and an Fr6 double-J stent was placed under the nephroscope. The rest of the procedure was identical to the description above for the PI-DJS group. Study outcomes The primary outcome measure is time to establish pas- sage for PCNL, whereas a secondary outcome measure is incidence of complications, including pneumothorax, postoperative fever, significant hemorrhage and need for blood transfusion. Statistical analysis All data were analyzed using SPSS 20.0 statistical software. Analyses and comparisons of the following characteristics were conducted between the two meth- ods: duration to establish the passage, duration of the operation, level of hemoglobin decline, rate of stone clearance, and perioperative complications. All data were expressed as the mean ± standard deviation (x ± s). T-tests were used for comparisons between the two groups. Chi-square (x2) tests were used to compare the rates or proportions among different subgroups. A Figure 1. The CONSORT flow diagram. PI-DJS: Preemptive indwelling of double-J stent group; PI-UC: Conventional Pre-emptive indwelling of ureteral catheter group. RCT of preemptive Dj in PCNL-Bai et al. p-value < 0.05 was considered to be statistically sig- nificant. RESULTS Characteristics of the Patient Population The characteristics of patients included in the trial are summarized in Table 1. No significant difference was found between patients allocated to PI-DJS and PI-UC groups, in terms of age (PI-DJS vs PI-UC: 48 ± 12.2 vs 47.7 ± 13.4), sex (27 male/10 female vs 28 male/10 female), affected side of kidney (20 left, 17 right vs 21 left, 17 right), size of stone (29.7 ± 4.4 vs 28.5 ± 4.7), percentage of staghorn stones (21.6% vs 23.7%) and stone locations (upper calyx 18 vs 13; middle calyx 19 vs 15; lower calyx 26 vs 29). Study Outcomes All patients underwent successful PCNL. The PI-DJS group (7.5 ± 2.0 min) showed significantly shorter du- ration to establish the PCNL passage when compared with PI-UC group (11.5 ± 2.5 min). However, there were no significant differences in other parameters, namely, the duration of operation, level of hemoglobin decline, incidence of complications and rate of stone clearance. A summary of the clinical outcomes for the two groups is shown in Table 2. In the PI-DJS group, pneumothorax occurred in one pa- tient after the removal of the nephrostomy tube and the patient was successfully treated via chest drainage. Fe- ver was observed in two patients, without occurrence of septic shock, who were then successfully treated with antibiotics. In the PI-UC group, surgery was aborted in one patient due to surgical vision field impairment as a result of bleeding. In another case, bleeding was found 4 days after the surgery, which was administrated with treatments including absolute bed rest, transfusion and hemostatic therapies. Postoperative infection was ob- served in two cases, but the conditions improved upon administration of sensitive antibiotic therapies. In the PI-UC group, there were 2 cases where the place- ment of a double-J stent into the bladder was unsuccess- ful. The stents were finally removed under ureteroscope with intravenous anesthesia. When appropriate, patients who had residual stones after one-stage nephrolithoto- my were administrated with second-stage treatments. Such procedures include extracorporeal shock wave lithotripsy, flexible ureteroscopic lithotripsy and two- stage PCNL. DISCUSSION PCNL was first reported by Fernstom and Johansson in 1976(1). The establishment of the percutaneous passage enabled larger stones to be disintegrated prior to their removal. This revolutionized the conventional con- cept that larger kidney stones could only be removed by open surgery(11). After more than 40 years of devel- opment, the procedures of PCNL have gradually been Table 1. Comparison of preoperative data between the two groups of patients PI-DJS (n=37) PI-UC (n=38) P value Age (Year); mean±SD 48.3±12.2 47.7±13.4 P = 0.762 Gender; N P = 0.944 Male 27 28 Female 10 10 Affected Side; N X2 = 0.011, P = 0.916 Left Kidney 20 21 Right Kidney 17 17 Stone diameter (mm); ; mean±SD 29.7 ± 4.4 28.5 ± 4.7 t =1.141; P = 0.258 Percentage of staghorn stones 21.6% 23.7% X2 = 0.045, P = 0.831 Stone location; N X2 = 1.144, P = 0.565 Upper calyx 18 13 Middle calyx 19 15 Lower calyx 26 29 All measurement data are expressed as the mean ± standard deviation or numbers unless otherwise specified. T-tests were used for com- parisons between the two groups. Chi-square (X2) tests were used to compare the rates or proportions among different subgroups PI-DJS (n=37) PI-UC (n=38) P Value Duration to establish passage (min) 7.5 ± 2.0 11.5 ± 2.5 P < 0.001 Duration of operation (min) 75 ± 45 79 ± 46 P = 0.704 Rate of Hemoglobin decline (g/L) 15.6 ± 3.4 16.2 ± 5.3 P = 0.562 Incidence of Complications (%) 13.5 13.2 P = 0.781 • Pneumothorax 1 0 Clavien II • Postoperative fever (>38.5° C) 2 2 Clavien II • Significant hemorrhage 2 3 Clavien II • Blood transfusion 0 1 Clavien II Rate of Stone Clearance(%) 81.1 78.9 P = 0.817 All measurement data are expressed as the mean ± standard deviation (x ± s). T-tests were used for comparisons between the two groups. Chi-square (X2) tests were used to compare the rates or proportions among different subgroups Table 2. Comparison of postoperative data between the two groups of patients RCT of preemptive Dj in PCNL-Bai et al. Endourology and Stones diseases 234 Vol 17 No 03 May-June 2020 235 standardized(11). Initially, the patient was placed in the lithotomy position. Retrograde insertion of the ureter- al catheter through the affected kidney via the urinary tract should be completed before the patient was placed in the prone position(12). Conventional PCNLs were usu- ally guided by X - ray technology to determine localiza- tion. In recent years, B-ultrasound localization has seen higher adoption due to its enhanced accuracy, reliabili- ty, and safety(13). A ureteral catheter was infused with physiological sa- line to create an artificial hydronephrosis. The puncture of the renal calyx was performed under the guidance of ultrasound, whereas expansion of the punctured pas- sage by renal sheath or balloon dilatation was carried out under the guidance of zebra urological guidewire. A lithotripsy was conducted after the establishment of the percutaneous renal puncture passage. In conven- tional PCNL, several uncertainties were frequently en- countered. In the process of establishing the operation passage for PCNL, saline was infused via a pre-set ure- teral catheter to create an artificial hydronephrosis, but microbubbles were consequently generated. These bub- bles then interfered with the ultrasound imaging which, in turn, may have affected the success of the calyceal puncture. Sometimes, problems such as inaccurate or difficult positioning of the double-J stent may occur toward the end of the surgery during the antegrade in- sertion of the stent as a result of a poor visual field or an inadequate angle between the ureter and the percu- taneous puncture. The current study unveiled that the major advantage of the preemptive indwelling of double-J tubes over the conventional preemptive indwelling of ureteral cath- eters was that the establishment of the percutaneous passage was significantly shortened. When saline per- fusion reached a height of 60 ~ 80cm, the reflux prop- erties of the double-J tube caused the renal collecting system to produce a stable artificial hydronephrosis with no appearance of microbubbles. This condition enhanced a stable B-ultrasound imaging, making it con- ducive for calyceal puncture with close to a 100% suc- cess rate. Hence, there was reduced interference under B-ultrasound and a shortened time spent for the percu- taneous renal puncture and the establishment of a work- ing passage. Due to persistent perfusion, the indwell- ing double-J procedure was less likely to form blood clots, which provided a clearer surgical vision field and a reduction in the number of accidental injuries to the renal system during laser lithotripsy. Additionally, PI- DJS prevented blindness during antegrade indwelling and ensured more reliable and accurate positioning. The present study concluded that PI-DJS was a safe and fea- sible method during PCNL. In some scenarios of pyelolithiasis where the ureter- opelvic junction was obstructed, the upper end of the double-J stent failed to coil in the renal pelvis; in such cases, the safety guide wire was first inserted under ureteroscopy to guide the subsequent indwelling of the double-J stent. When using the double-J stent, contin- uous perfusion, calyceal puncture, expansion of the punctured passage, and even the lithotripsy were much easier to achieve. In contrast to conventional PCNL, the newer method was less prone to clot formation and had a clearer visual field. This enhanced surgical safety and reduced the occurrence of accidental mucosal injuries to the renal collecting system. In addition, PI-DJS also significantly shortened the operative time, a risk factor for surgical site infection. PI-DJS prevented antegrade indwelling when used in the conventional way. In one conventional case, the patient’s fragmented stones blocked the ureter and pre- vented placement of the guide wire into the bladder. The double-J stent could only be placed after the patient was in the lithotomy position. In a different case, the placement of the guide wire into the ureter failed as a result of an inadequate angle between the ureter and the inferior renal calyceal puncture. Similarly, the double-J stent was successfully placed after the patient assumed the lithotomy position. It is noteworthy that sheaths should be used during PCNL to prevent laser damage to the wall of the double-J stent, so as not to affect the effect of drainage and formation of mural stones after operation(14). CONCLUSIONS To summarize, our study shows that the PI-DJS is more advantageous than the conventional PCNL due to short- ened time to establish passage (7.5 mins in PI-DJS vs 11.5 mins in PI-UC) for PCNL and no increase in the incidence of complications. Given that the current study has a limited sample size, a multi-center, large-scale, prospective, randomized, and controlled trial is war- ranted to further confirm observations from the present study. ACKNOWLEDGEMENTS This work was supported by grants from Zhejiang Provincial Natural Science Foundation of China (No. LY18H040007 to Jiaming Wen) and National Natural Science Foundation of China (No. 81871153 to Jia- Ming Wen) and Zhejiang provincial science and Tech- nology Department (No. 2017C33063 to Fuding Bai). CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. Fernstrom I, Johansson B. Percutaneous pyelolithotomy. A new extraction technique. Scand J Urol Nephrol. 1976;10:257-9. 2. Ganpule AP, Vijayakumar M, Malpani A, Desai MR. Percutaneous nephrolithotomy (PCNL) a critical review. Int J Surg. 2016;36:660-4. 3. Hosseini MM, Hassanpour A, Eslahi A, Malekmakan L. 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