A Novel Ureterorenoscope for the Management of Upper Urinary Tract Stones: Initial Experience from a Prospective Multicenter Study.

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Journal of Endourology A novel ureterorenoscope for the treatment of upper urinary tract stones: initial experience from a prospective multicentre study (doi: 10.1089/end.2015.0046) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

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Title Page Title: A novel ureterorenoscope for the treatment of upper urinary tract stones: initial experience from a prospective multicentre study Authors *Xiaofeng Gao, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433. *

Guohua Zeng, Department of Urology; the First Affiliated Hospital of Guangzhou Medical University, No. 151, West Yanjiang Rd, Guangzhou, China, 510405.

*Hequn Chen, Department of Urology; Xiangya Hospital, Central South University, No. 87, Xiangya Rd, Changsha, China, 410008. *Yue Cheng, Department of Urology; Ningbo First Hospital, Ningbo University, No. 59, Liuting Rd, Ningbo, China, 315010. *Kunjie Wang, Department of Urology; West China Hospital, Sichuan University, No. 37, Guoxue Rd, Chengdu, China, 610041. *JianXing Li, Department of Urology; Tsinghua Changgung Hospital, Tiantong Yuan, Changping District, Beijing, China, 100000. *Lei Shi, Department of Urology; Yantai Yuhuangding Hospital, Affiliated Hospital of Medical College, Qingdao University, No. 20, Easten Yuhuang Ding Rd, Yantai, China, 264000. Ling Li, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433. Yonghan Peng, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433. Min Liu, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433. Qiheng Wang, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433. Chuanliang Xu, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433. 1

Yinghao Sun, Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433.

*These authors contributed equally to this work 1

Corresponding author: Yinghao Sun

Address: Department of Urology; Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Shanghai, China, 200433 Email: [email protected]

Running head: Multicentre study of a novel ureterorenoscope Key Words: ureteroscopy; ureteral stones; renal stone

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2 ABSTRACT Purpose: This prospective single-arm multicentre clinical trial was conducted to evaluate the safety and efficacy of the Sun’s tip-flexible semirigid ureterorenoscope (tf-URS) when used for treating upper urinary tract stones. Materials and Methods: Data from patients who underwent ureteroscopy using the tf-URS for proximal and renal stone removal were prospectively collected from seven Chinese clinical centers. The primary study endpoint was the stone clearance at the 2-week follow-up. Other data associated with the procedure were also collected. Results: Between October and December of 2014, this study enrolled a total of 254 patients; among which, 235 patients were eligible for ureteroscopy, and 216 of whom were treated using the tf-URS. Among all treated patients, 135 had proximal ureteral stones (group 1) while 81 had renal stones (group 2). The overall success rate of endoscope advancement was 91.9% (216/235). The mean fragmentation times were 17.5 ± 12.6 min and 23.3 ± 15.1 min for groups 1 and 2, respectively, and corresponded to an experience-dependent increase in fragmentation speed in both groups. The mean operation times were 31.9 ± 15.5 min and 39.5 ± 2 0.3 min for groups 1 and 2, respectively. The access rate to renal stones in group 2 was 96% (76/81). All treated patients were assessed during a 2-week follow-up period. The stone free rates at the 2-week follow-up for groups 1 and 2 were 98.7% (133/135) and 91.3% (74/81), respectively. Adverse events were observed in 7.3% (16/216) of the patients; however, all were classified as Grade 1 or Grade 2 complications. Conclusions: Based on our initial experience in the current study, the tf-URS can be safely and effectively used to treat proximal ureteral and renal stones with a low rate of complications. Future studies are required to focus on a transverse comparison between the tf-URS and conventional

Journal of Endourology A novel ureterorenoscope for the treatment of upper urinary tract stones: initial experience from a prospective multicentre study (doi: 10.1089/end.2015.0046) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. Page 3 of 22

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ureteroscopes.

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4 INTRODUCTION Due to technical improvements and the introduction of various new accessories, ureteroscopy has become an alternative to extracorporeal shockwave lithotripsy and percutaneous nephrolithotomy for treating upper urinary tract stones (UUTS). In 2012, the European Association of Urology (EAU) recommended endourology as first-line treatment for UUTS < 2.0 cm, and since that time, the feasibility and efficacy of the ureteroscopic approach have been widely accepted.1,2 Ureteroscopes are commonly divided into two categories based on their structure. A semirigid ureteroscope (r-URS) is suitable for treating distal or mid- ureteral stones.3 However, due to its straight metal shaft that cannot be deflexed, a r-URS is not capable of treating renal stones. A flexible ureteroscope (f-URS) has totally flexible shaft and active deflection, thus is suitable for removing renal stones and proximal ureter stones. However, a f-URS still has some disadvantages including its poor maneuverability and the difficulty of insertion into the ureter.4 In 2013, we developed a novel endoscopic device that integrated the functions of both the r-URS and f-URS, and named it the Sun’s tip-flexible semirigid ureterorenoscope (tf-URS). The current study was conducted to evaluate the impact of this new device on the clinical outcomes when treating UUTS.

MATERIALS AND METHODS 2.1 Patients Data from consecutive patients who underwent ureteroscopy using the tf-URS for proximal and renal stone removal were prospectively collected from seven clinical centers in China (Changhai Hospital of the Second Military Medical University; the First Affiliated Hospital of Guangzhou

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5 Medical University; Xiangya Hospital of Central South University; Ningbo First Hospital of Ningbo University; West China Hospital of Sichuan University; Tsinghua Changgung Hospital; Yantai Yuhuangding Hospital of Qingdao University). All sites obtained study approvals from their ethics committees, and the patients were counseled concerning the purpose and risks of the study and provided a signed Informed Consent. The main eligibility criterion was stones < 2 cm in size. Additional details pertaining to the inclusion and exclusion criteria are listed in Table 1. 2.2 Study design This study was an open-label, prospective, multicentre, single-arm trial that enrolled patients from seven clinical centers in China. Figure 1 shows a flowchart for the study, including its treatment and follow-up phases. The primary study endpoint was the stone clearance at a 2-week follow up visit. For purposes of this study, “stone free” was defined as the patient having gravel particles < 0.2 cm in size. Data was also collected for the following parameters: (1) the stone clearance on the first post-operative day; (2) endoscope advancement results; (3) the time associated with the surgery, including the full operation time, endoscope advancement time, the total time needed to inspect the collecting system of the renal stone patients, and the fragmentation time; (3) the requirement for stone relocation to facilitate fragmentation of renal stones; (4) adverse events and their classifications according to the modified Clavien-Dindo grading system;5 (5) postoperative treatments including the postoperative stay, any secondary treatments, and the need for re-admission within two weeks after surgery; (6) endoscope damage and endoscope repair frequency. 2.3 Endoscopic device The tf-URS (SN-V, Hawk Endoscopes, China) has been approved for clinical applications by

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6 the China Food and Drug Administration. The design of the tf-URS is unique in that it consists of a retractable rigid sheath and a semirigid ureteroscope with a 9-cm flexible part on the tip (Figure 2). The rigid/flexible working modes can be switched by releasing the flexible tip. Duel 250°/270° deflection can be manipulated by the lever on the handle. The tf-URS is 8.2/8.7 Fr in diameter at the tip of the inner-shaft/outer-sheath, and 9.8 Fr in diameter at the bottom of the sheath. It also has a 3.6 Fr working channel for auxiliary instruments. In addition, the tf-URS contains an independent outflow channel along the interspace between the shaft and the sheath that enables continuous outflow. 2.4 Preoperative treatments Several examinations were performed prior to each surgery, and the subjects were restricted to those with mild or moderate hydronephrosis (< 3 cm in size) based on their ultrasonography results. Stone burden was calculated as the sum of the sizes of all stones size (length × width × 0.25 × 3.14159) as seen on X-ray and intravenous urography. Computed tomography was also performed to evaluate stone burden and location when a subject had radiopaque stones or faint X-ray results. All patients received a single dose of antibiotic (ciprofloxacin) if their urine culture showed negative results; otherwise, they were continued on a sensible antibiotic regimen until their culture results were negative. Patients who had ipsilateral pre-stenting or a previous ureteroscopy within the previous six months were excluded from the study. 2.5 Surgical procedures Each clinical site had one fixed surgeon and two assistants. All surgeons were skilled in semirigid and flexible ureteroscopy, and had previously treated > 500 cases. Retrograde ureteroscopy was performed in a supine lithotomy position under general anesthesia,

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7 and irrigation was provided by one assistant using a syringe. The tf-URS was advanced through the ureter along the guide wire under visual and fluoroscopic guidance. For subjects with proximal ureteral stones, the 200 μm laser fiber was introduced to proceed with stone disintegration after the safety wire was in place. Pulse settings began at 0.6 J and a frequency of 15 Hz, and were increased to 1.0 J at 15 Hz if the stone was hard. The tf-URS was maintained in “rigid mode” during the procedure within the ureter. For patients who had renal stones or in whom proximal ureteral stone retropulsion was encountered, the tf-URS was further advanced into the renal pelvis. The endoscope was then switched to “flexible mode” by extending the tip of the inner flexible shaft. After fully inspecting the collecting system and determining stone location, disintegration was performed using the 200 μm laser fiber at settings of low energy and high frequency. Stone dusting was considered to be satisfactory when each piece of gravel was < 0.2 cm. Subsequently, fluoroscopy was used to detect the presence of any residual fragments. After extracting a single fragment for component analysis, the tf-URS was withdrawn along the guide wire, and a 6 Fr D-J stent was routinely placed. 2.6 Postoperative treatments and follow-up All subjects underwent antibiotic therapy after surgery, and X-rays were performed on the following day. At the 2-week follow-up visit, the D-J stent was removed by cystoscopy and the final SFR was assessed by X-ray.

RESULTS 3.1 Study population Between October and December, 2014, a total of 254 subjects were recruited, of whom 14 were

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8 excluded based on exclusion criteria. The remaining 240 patients underwent preoperative preparation; however, five patients were deemed ineligible due to refractory urinary infections. Finally, a total of 235 eligible patients underwent ureteroscopy; of whom 216 were treated using the tf-URS. All treated patients were available for the 2-week follow-up visit and completed the study. Basic characteristics of the treated patients are summarized in Table 2. 3.2 Features of the stones Among the 216 treated patients, 135 had proximal ureteral stones (group 1), and the remaining 81 patients had renal stones (group 2). The average number of stones per patient was 1.4 ± 0.8 (range: 1–4), and the mean stone size was 1.4 ± 0.5 cm (range: 0.4–2.0 cm). Among subjects with renal stones, the stone locations included upper calyx (9.8%, 8/81), middle calyx (8.6%, 7/81), lower calyx (13.6%, 11/81), renal pelvis (40.7%, 33/81) and multiple sites (32.1%, 26/81). Among all stones, 81% were composed of oxalate, while the others were composed of phosphate (8%), uric acid (8%) or were mixed stones (3%). Details of the stone features are listed in Table 2. 3.3 Endpoints When including all treated subjects (except 19 who failed endoscope introduction), the immediate SFR on the first postoperative day was 94.0% (203/216), and the final SFR at the 2-week follow-up visit was 95.8% (207/216). Data pertaining to these outcomes are shown in Table 3. 3.4 Perioperative results The overall success rate for endoscope advancement was 91.9% (216/235). The mean time for endoscope advancement in group 1 was 2.9 ± 1.5 min (range: 1.0-8.0 min, from insertion into the ureter to arrival at the ureteral stone) and 3.0 ± 1.6 min in group 2 (range: 1.0-5.5 min, from

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9 insertion into the ureter to arrival at the renal pelvis). The mean time required to inspect the collecting system for group 2 subjects was 2.3 ± 0.7 min (range: 1.5–8.0 min), and the stone access rate for group 2 subjects was 96.0% (78/81). The mean fragmentation times were 17.5 ± 12.6 min (range: 2.0-75 min) and 23.3 ± 15.1 min (range, 12.0-60.0 min, including stone relocation using the basket) for groups 1 and 2, respectively; which corresponded to mean fragmentation speeds of 8.1 ± 3.0 mm2/min and 7.3 ± 1.7 mm2/min, respectively. The mean operation times (including placement of the D-J stents) in groups 1 and 2 were 31.9 ± 15.5 min (range: 10.0–96.0 min) and 39.5 ±20.3 min (range: 15–92 min), respectively. Stone retropulsion during the lithotripsy was encountered in 21.5% (29/135) of all group 1 patients, and necessitated further advancement of the tf-URS into the renal pelvis to continue surgery. Among all group 2 patients, 33.3% (8/24) had stones located at the lower calyx that could not be re-entered when the laser fiber was introduced and these cases required stone relocation using a basket. Stones access was not completed in three patients of whom the renal stones located at the lower calyces. These three cases had small infundibulopelvic angles (3.5 cm). For the three patients, we changed our procedures and used conventional flexible ureteroscopes, however this conversion did not permit stone access either. The mean length of the postoperative stay for all patients was 1.9 ± 1.1 d (range: 1-8 d) and 1.4% (3/216) of patients required a second procedure. Data pertaining to the perioperative results are presented in Table 3. 3.5 Complications All adverse events classified by the modified Clavien-Dindo grading system are presented in

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10 Table 4. Complications were observed in 7.3% (16/216) of all patients. Grade 1 complications were observed in 11 (5.1%) patients, and included moderate pain, hematuria, and other types of discomfort. Grade 2 complications were observed in five (0.5%) patients, and included fever, severe pain, and postoperative obstruction. One patient was re-admitted for acute obstruction after D-J stent removal at the 2-week follow up, but later expelled the stones after medical expulsive therapy. No Grade 3 or Grade 4 complications were observed in the current study. 3.6 Endoscope damage There were three endoscope failures in the study. One endoscope lost one-way deflection when treating the lower pole stone after six times of usage. Leakage of the working channel was observed in another endoscope caused by the improper operation of the surgeon (laser fiber accidental injury) after 21 times of usage. One other endoscope generated more than five black dots on endoscopic images, however this issue had no significant effects on procedures.

DISCUSSION During the past several decades, the management of UUTS has been significantly impacted by substantial improvements in the surgical treatment armamentarium. In 2003, we developed a first generation tf-URS for use in retrograde ureteral and intrarenal surgeries, and demonstrated its efficacy by achieving an 83% SFR at one month post-surgery.6 To the best of our knowledge, this ureterorenoscope was the first to integrate advantages associated with the use of both rigid and flexible ureteroscopes. In 2013, we presented a new version of the tf-URS, and named it the Sun’s tip-flexible semirigid ureterorenoscope. We conducted the current study to evaluate the

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11 ureteroscopic outcomes achieved when using this novel device for treating UUTS. Because treatment of larger stones required a prolonged operation time and involved an increased risk for tissue damage, the American Urological Association/European Association of Urology suggested that ureteral and renal stones treated using an endoscopic approach should be limited to 2 cm in size,1,7 and thus stone size was restricted to 2 cm in the current study. Whether or not stone fragments should be retrieved remains controversial.8 The tf-URS must be withdrawn back into the bladder and subsequently re-advanced in order to extract stone fragments. This process could be time consuming and increased the risk for tissue damage;9 we therefore preferred stone dusting rather than stone extraction. Due to its straight metal shaft, the r-URS is considered to be maneuverable. When the tf-URS is maintained in the “rigid mode” with the flexible tip withdrawn in the sheath, it can be manipulated in a manner identical to a conventional r-URS, and is capable of passing either the orifice or the physiological tortuosity of the ureter with ease like a r-URS. The tf-URS is 8.2/8.7 Fr in diameter for the inner-shaft/outer-sheath at the tip and is 9.8 Fr at the bottom of the sheath, which is larger than the commercially latest available flexible ureteroscopes and even smaller semirigid ureteroscopes. However, according to the European Association of Urology guidelines,1 a ureter access sheath (UAS) is recommended in flexible ureteroscopy. When compared with the most common used UAS (12/14 Fr), the tf-URS is smaller, which indicates that retrograde intrarenal surgery using the tf-URS does not require a larger caliber of the ureter than a common flexible ureteroscopy. Although the smallest semi-rigid ureteroscope is only 4.5 Fr in diameter, the most common used semirigid ureteroscope in China is the 8/9.8 Fr endoscope (8703.534, Wolf, Germany) that is similar to the tf-URS in endoscopic caliber. In our study, the success rate of

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12 endoscope advancing was 91.9% and the stone free rate for proximal stones was 98.7%. These results were comparable to common ureteroscopic outcomes that has been reported,10 which indicated that the caliber of the tf-URS did not significantly influence the outcomes for the treatment of upper urinary tract stones. The clinical Research Office of the Endourological Society recently reported that the overall SFR for proximal ureteral stones treated with ureteroscopy was 84.5%,11 but decreased to 63.4% when only a r-URS was available. This result is thought to be attributable to potential retropulsion.7,12 In the current study, stone retropulsion was observed in 21.5% (29/135) of the patients with a proximal ureteral stone. In these cases, the tf-URS could be further advanced up to the renal pelvis without assistance from the UAS, and then switched to the “flexible mode” to complete the disintegration of migrated stones. Surgeons only needed to make a simple thumb motion to control the duel deflection of the flexible tip. In this study, the SFR for proximal ureteral stones treated using the tf-URS was 98.7% (133/135), which was significantly higher than the SFR achieved using a conventional r-URS as other investigators reported,12 indicating that the tf-URS is suitable for treating proximal ureteral stones. Nordahl13 demonstrated that the 270°f-URS provided increased access to lower calyces and a higher SFR compared to that achieved using a 180°f-URS; suggesting that high deflection is essential for better results.14 When working in the “flexible mode,” the tf-URS has a dual active deflection of 250°/270° (up and down) at the tip, and this is similar to the majority of commercially available f-URSs.15 Therefore, the tf-URS is capable of treating renal stones in various calyces. In the current study, the stone access rate was 96.0% (78/81). Consistent with results from previous studies,13,14,16 the tf-URS also showed some deflection loss when an

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13 auxiliary instrument was introduced; nevertheless, a high deflection was still retained. Re-location of lower pole stones with a 1.7 F basket could still be achieved in all patients with stones located at the lower pole calyces that could not be accessed when the laser fiber was inserted. Although the treatment procedures for three patients were changed to use a flexible ureteroscope when the tf-URS could not access the lower pole calyces, the conversion did not allow us to complete these procedures due to the complicated location. The final SFR for renal stones was 91.3% (74/81), which is similar to that reported for flexible ureteroscopy,17 and suggests that the tf-URS can achieve good renal stone clearance. It may be argued that the full inspection and the disintegration times in our study were still quite long when compared to those achieved using conventional ureteroscopes; however, these times were reduced as the experience of the surgeons increased (Figure 3a). Additionally, the mean fragmentation speeds for proximal ureteral stones and renal stones were 8.1 ± 3.0 mm2/min and 7.3 ± 1.7 mm2/min, respectively, and showed obvious improvements with increased operative experience (Figure 3b). These results may reflect a rather short tf-URS learning curve for surgeons with previous f-URS experience. Similar to conventional URS, ureteroscopy using the tf-URS was initiated in a natural orifice suitable for performing transluminal endoscopic surgery, and thus had a very low rate of complications.18 Adverse events were observed in 7.3% (16/216) of all patients, and were classified as either Grade 1 or Grade 2 complications. Unlike other investigator reports regarding use of the f-URS,9 there were no perforations or severe ureteral wall injuries in any of the cases in the current study. This is likely attributable to our use of “vision-guided endoscope advancement,” which allowed the surgeons to obtain clear images and avoid perforations.

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14 There are three notable limitations of the current study. First, this single-arm study may have produced less convincing results when compared to those that might have been shown by a controlled trial; however, our initial clinical experience indicated that the novel endoscope provided a satisfactory SFR accompanied by few complications; which is quite encouraging. A prospective randomized controlled trial is currently being planned, and will soon be conducted to provide a better comparison of the conventional and new endoscopic techniques. A second limitation is the exclusion of patients with hydronephrosis > 3 cm on ultrasonography. The presence of severe hydronephrosis would significantly increase the difficulty of surgery, even when using a f-URS with a totally flexible shaft. The length of the flexible portion of the tf-URS is 9 cm, which makes if difficult to fully inspect the collecting system in subjects with severe hydronephrosis. The clinical conditions best treated by ureteroscopy with the tf-URS are still being determined, and further studies are required to focus on this issue. The third limitation of this study is its relatively short follow-up period. However, we noticed that most of the subjects had already shown rather favorable outcomes within two weeks after surgery. Additionally, as summarized in the EAU guidelines,1 the complication rates for URS range from 9% to 25%, and most complications are observed during the intraoperative or early postoperative periods. The late complication rate is only 0.2%, which accounts for a very small proportion of the total complications. These two facts suggest that the follow-up duration used in our current study was sufficient to evaluate the safety and efficacy of the new device.

CONCLUSION

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15 As a novel ureterorenoscope that integrates the functions and advantages of both the r-URS and f-URS, the tf-URS provides a simple means of performing retrograde ureteral and intrarenal surgery, and was proven capable of safely and effectively treating proximal ureteral and renal stones with a low rate of complications. A future controlled study is required to compare the tf-URS with conventional ureteroscopes.

ACKNOWLEDGMENTS This work was supported by the National “863” High Tech Program of China (2012AA021102).

DISCLOSURES The authors declare having no conflicts of interest regarding the design or conduct of this study. This work was supported by the National “863” High Tech Program of China (2012AA021102).

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16 REFERENCES 1.

C. Türk TK, A. Petrik, K. Sarica, et al. 2014 Guidelines on Urolithiasis. European Association of

Urology. 2.

Aboumarzouk OM, Monga M, Kata SG, et al. Flexible ureteroscopy and laser lithotripsy for

stones >2 cm: a systematic review and meta-analysis. J Endourol 2012;26:1257-1263. 3.

de la Rosette J, Denstedt J, Geavlete P, et al. The clinical research office of the endourological

society ureteroscopy global study: indications, complications, and outcomes in 11,885 patients. J Endourol 2014;28:131-139. 4.

Geavlete P, Multescu R, Geavlete B. Pushing the boundaries of ureteroscopy: current status and

future perspectives. Nat Rev Urol 2014;11:373-382. 5.

Yoon PD1, Chalasani V, Woo HH. Use of Clavien-Dindo classification in reporting and grading

complications after urological surgical procedures: analysis of 2010 to 2012. J Urol 2013 190:1271-1274. 6.

Yinghao S, Yang B, Gao X. The management of renal caliceal calculi with a newly designed

ureteroscope: a rigid ureteroscope with a deflectable tip. J Endourol 2010;24:23-236. 7.

Glenn M. Preminger DSG, Dean G. Assimos, Gary Curhan, et al. Medical Management of Kidney

Stones: AUA Guideline. American Urological Association. 8.

Rebuck DA, Macejko A, Bhalani V, et al. The natural history of renal stone fragments following

ureteroscopy. Urology 2011;77:564-568. 9.

Traxer O, Thomas A. Prospective evaluation and classification of ureteral wall injuries resulting

from insertion of a ureteral access sheath during retrograde intrarenal surgery. J Urol 2013;189:580-584. 10. Atis G, Arikan O, Gurbuz C, et al. Comparison of different ureteroscope sizes in treating ureteral calculi in adult patients. Urology 2013;82:1231-1235. 11. Perez Castro E, Osther PJ, Jinga V, et al. Differences in ureteroscopic stone treatment and outcomes for distal, mid-, proximal, or multiple ureteral locations: the Clinical Research Office of the Endourological Society ureteroscopy global study. Eur Urol 2014;66:102-109. 12. Karadag MA, Demir A, Cecen K, et al. Flexible ureterorenoscopy versus semirigid ureteroscopy for the treatment of proximal ureteral stones: a retrospective comparative analysis of 124 patients. Urol J 2014;11:1867-1872. 13. Wendt-Nordahl G, Mut T, Krombach P, et al. Do new generation flexible ureterorenoscopes offer a higher treatment success than their predecessors? Urol Res 2011;39:185-188. 14. Wendt-Nordahl G, Trojan L, Alken P, et al. Ureteroscopy for stone treatment using new 270 degrees semiflexible endoscope: in vitro, ex vivo, and clinical application. J Endourol 2007;21:1439-1444. 15. Geavlete P, Multescu R, Geavlete B. Retrograde flexible ureteroscopic approach of upper urinary tract pathology: What is the status in 2014? Int J Urol 2014;21:1076-1084. 16. Bedke J, Leichtle U, Lorenz A, et al. 1.2 French stone retrieval baskets further enhance irrigation flow in flexible ureterorenoscopy. Urolithiasis 2013;41:153-157. 17. Somani BK, Al-Qahtani SM, de Medina SD, et al. Outcomes of flexible ureterorenoscopy and laser fragmentation for renal stones: comparison between digital and conventional ureteroscope. Urology 2013;82:1017-1019. 18. Ozsoy M, Acar O, Sarica K, et al. Impact of gender on success and complication rates after


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ureteroscopy. World J Urol 2014. Nov 12. [Epub ahead of print]

Inclusion criteria

r-URS: semirigid ureteroscope f-URS: flexible ureteroscope tf-URS: Sun’s tip-flexible semirigid ureterorenoscope SFR: stone free rate UAS: ureteral access sheath UUTS: upper urinary tract stones

Table 1. Patient selection criteria

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18  Subject has provided informed consent and indicated a willingness to comply with study procedures and policies  Subject has a diagnosis of proximal ureteral stones or renal stones according to CT and IVU results Parameter  Subject is a candidate for ureteroscopic surgery Age, yr 49.3 ±12.1  Subject is 18–80 yrs of age Gender, No. of patients  Subject has a single stone < 2 cm in size (IVU), or multiple stones 3 cm according to a B-scan ultrasonography examination CT = Computerized Tomography IVU = Intravenous Pyelography

Table 2. Patient characteristics and stone features

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19 Middle calyx Lower calyx Multiple Parameter, % ( No.) Parameter Stone size, cm Intraoperative complication Proximal ureter Bleeding success rate, % (No.) Advancement Kidney Postoperative Endoscope complication advancement time, min No. of stones Hematuria Collecting system inspection time, min Proximal ureter Pain/discomfort Success rate of stone access, % (No.) Kidney Fever Fragmentation time, min Stone composition, % (No. of2 patients) Obstruction Fragmentation speed, mm /min Oxalate stones Operation time, min Data are mean ±SEM Phosphate Stone retropulsion, % (No.) Uric acid Final stone free rate, % (No.) Mixed Post-operative stay, d Data are mean ±SEM Re-admission < 1 month, % (No.)

2.9 (7/235) 5.5 (13/235) 11.5 (27/235) Stone location 1.4 ±0.5 Ureter Kidney 1.3 ±0.6 93.7% (135/144)0.9% (2/216) 89.0% (81/91) 1.5 ±0.4 2.9 ±1.5 3.0 ±1.6 1.4 ±0.8 Not applicable 3.2% (7/216)2.3 ±0.7 1.3 ±0.6 Not applicable 4.2% (9/216) 96.0% (78/81) 1.7 ±0.9 17.5 ±12.6 1.9% (4/216) 23.3 ±15.1 0.5% (1/216) 8.1 ±3.0 7.3 ±1.7 81 (191/235) 31.9 ±15.5 39.5 ±20.3 19 (8/235) 21.5% (29/135) Not applicable 19 (8/235) 98.7% (133/135) 91.4% (74/81) 11 (26/235) 1.9 ±1.7 1.9 ±1.3 0% 0.5 (1/216)

Data are mean ±SEM

Table 3. Perioperative results and surgical outcomes

Table 4. Intraoperative and postoperative complications


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Figure 1. Study design


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Figure 2. Separate and assembled structures of the Sun’s tip-flexible semirigid ureterorenoscope


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Figure 3. Inspection and fragmentation times as related to the surgeon's ongoing level of experience

Group 1: patients with proximal ureteral stones; Group 2: patients with renal stones

Prediction of septicemia following endourological manipulation for stones in the upper urinary tract.

Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract stones: a randomized study. The Cefotaxime Cooperative Group.

[Surgical management for upper urinary tract transitional cell carcinoma].

Management of lower ureteric stones: a prospective study.

Ureteroscopy for treatment of upper urinary tract stones in children: technical considerations.

Protective temporary vesicostomy for upper urinary tract problems in children: a five-year experience.

Initial experience and treatment of atrial fibrillation using a novel irrigated multielectrode catheter: Results from a prospective two-center study.

Regional variations in the incidence of upper urinary tract stones in England and Wales.

Upper urinary tract lipoma: A case report.

Management of upper gastrointestinal bleeding in emergency departments, from bleeding symptoms to diagnosis: a prospective, multicenter, observational study.

Management of postoperative fistula of upper urinary tract.

[Flexible laser ureteroscopy in the treatment of upper urinary tract stones: results about 166 interventions].

The dilated upper urinary tract.

Palliative management of malignant upper urinary tract obstruction.

The dilated upper urinary tract.

Retroperitoneoscopic versus open mini-incision ureterolithotomy for upper- and mid-ureteric stones: a prospective randomized study.

Initial experience with sacral neuromodulation for the treatment of lower urinary tract dysfunction in Brazil.

Compositional analysis of various layers of upper urinary tract stones by infrared spectroscopy.

Validation of Cefazolin as Initial Antibiotic for First Upper Urinary Tract Infection in Children.

The cold-knife technique for endourological management of stenoses in the upper urinary tract.

Initial experience with a novel EUS-guided core biopsy needle (SharkCore): results of a large North American multicenter study.

Fungal bezoars of the upper urinary tract.

Duplication of the upper urinary tract.

Urothelial carcinoma of the upper urinary tract.