Stesura Seveso Archivio Italiano di Urologia e Andrologia 2018; 90, 120 ORIGINAL PAPER semirigid ureteroscopy prior retrograde intrarenal surgery (rIrs) helps to select the right ureteral access sheath Ioannis Boulalas, Mauro De Dominicis, Lorenzo Defidio Department of Urology, Cristo Re Hospital, Rome; Italy. Objective: To evaluate ureteral compliance through semirigid ureteroscopy (sURS) in order to select the proper ureteral access sheath (UAS) size for retrograde intrarenal surgery (RIRS). Patients and methods: In a prospective study, 100 consecutive patients selected for elective sURS or RIRS were recruited. Each patient, initially underwent 9.5 Fr sURS with a safety guide- wire 3Fr, in order to estimate ureteral compliance. If the ureter was compliant, a gently passage of a 12/14Fr UAS was attempted. If the ureter was not deemed compliant, passage of either a smaller UAS or a smaller semirigid 7Fr or a flexible 7.5Fr or a digital 8.5Fr scope with and without safety guidewire, was attempted. Age, gender, disease location, pre- stenting, previous RIRS and/or stone elimination, hydronephro- sis, ureteral strictures, unsuccessful procedures, and complica- tions, were analyzed as possible correlated factors of ureteral compliance. Results: In 77 patients the ureter was deemed compliant ≥ 14Fr. Of the preoperative factors that were examined, stent placement before RIRS (P < 0.002), previous RIRS (P = 0.000) and previous stone elimination (P = 0.004), correlated with ureter ≥ 14Fr. Ureteral lithiasis (P < 0.001), ureteral strictures (P < 0.05), unsuccessful procedures (P < 0.005) and complica- tions (P = 0.01) correlated with ureter < 14Fr. The complica- tion rate was 10% (10 patients) with ureteral injuries grade I in 9 patients and grade III in 1 patient according to the endo- scopic grading system. Age, gender, hydronephrosis and urothe- lial carcinoma (UC) had no influence. Conclusions: sURS performed before RIRS allows selection of the right ureteral access sheath (UAS) and avoidance of major complications. Pre-stenting, previous RIRS and stone elimina- tion history are all factors correlating with a compliant ureter. KEy wORDS: Semirigid ureteroscopy; Retrograde intrarenal sur- gery (RIRS); Ureteral compliance; Ureteral access sheath (UAS). Submitted 8 November 2017; 19 November 2017 Summary No conflict of interest declared. Nowadays, retrograde intrarenal surgery (RIRS) (2, 3) is used in the treatment of urinary lithiasis (4), upper tract urinary tumors (5, 6), as well as in special circumstances such as pregnancy, anatomic malformations, coagulopa- thy or solitary kidney (7, 8). Urinary stones disease poses a significant health care burden in a working-age population. A recent analysis of National Health and Nutrition Examination Survey (NHANES) data in the United States from 2007 to 2010 reported that the prevalence had increased to 8.8% (10.6% among men vs 7.1% among women), compared with 5.5% in NHANES III (1988-1994) (9). Upper tract urothelial carcinoma (UTUC) constitutes approximately 5-6% of all urothelial malignancies. Ureteral tumors represent approximately 25% of UTUCs (10). In 2013, the European Association of Urology (EAU) for the first time included RIRS as a viable treatment option for renal stones, even larger than 2 cm in diameter (11). Moreover, the UTUC EAU Guidelines support renal-spar- ing surgery in imperative cases and low-risk patients (12). The ureteral access sheath (UAS) was introduced as a means of passing a flexible uretero-renoscope into the distal ureter. Its use also facilitates multiple re-entries into the kidney, improves fluid outflow, thereby reduc- ing the intrarenal pressure, decreases operative time, increases stone clearance, and protects the endoscope from damage (13, 14). However the routine use of a UAS is matter of debate (11). Limited data is available to predict which patients select- ed for RIRS may have a difficult ureter and in which cases success is most probable. The hypothesis that endoscopic evaluation of ureteral size may help urologists to select the proper UAS size for RIRS, was prospectively tested and possible correlating factors for success or failure were analyzed. PatIents and methods This study was carried out at ‘Cristo Re’ Hospital in Rome, after institutional review board approval was obtained, by two experienced urologists, who treated a similar number of patients. Both surgeons were present during the proce- dures, thus avoiding any difference in the assessment accuracy. A total of 100 consecutive patients (72 males and 28 females) between March 2016 and September 2016, with urinary lithiasis, upper urinary tract tumors, hematuria and ureteral stenosis planned for elective semi- DOI: 10.4081/aiua.2018.1.20 IntroductIon The management of intra-renal collecting system pathol- ogy has changed radically over the recent decades main- ly due to increasing use of flexible uretero-renoscopy (fURS), constituting one of the most dynamic fields of endourology. Thanks to technologic improvements in the endoscopic armamentarium, flexible uretero-reno- scopic approaches to the kidney have evolved from a mere diagnostic tool, to a complex diagnostic and thera- peutic procedure in the entire upper tract collecting sys- tem (1). 21Archivio Italiano di Urologia e Andrologia 2018; 90, 1 Semirigid ureteroscopy prior RIRS rigid ureterorenoscopy or RIRS were included in the study. All patients had a clinical evaluation, urine dipstix analysis with additional culture and sensitivity if a urinary tract infection (UTI) was suspected, a measurement of serum creatinine level, abdominal ultrasonography (US) and a plain abdominal X- ray. Additional computed tomog- raphy (CT) was used, according to the level of serum cre- atinine and stone radiolucency. Patients were placed in the lithotomy position and received prophylactic parenteral antibiotics before the procedure, which was performed under spinal or general anesthesia. The standard tech- nique was initiated with rigid cystoscopy, followed by ureteral catheterization of the renal unit in question with an end-hole 5Fr catheter (Pollack Cook Urological, Spencer, IN). A retrograde pyelogram was performed to define the anatomy and visualize any filling defect. A hydrophilic tipped guidewire 0.035/150 cm (Sensor®, Boston Scientific, Marlborough, MA, USA) was passed via the ureteral catheter, just to the renal pelvis under fluoroscopic guid- ance, and set aside as a safety wire, and then the cysto- scope and the retrograde catheter were removed. A second hydrophilic tipped guidewire was introduced into the ureteral orifice through the 9.5Fr Storz semirigid uretero- scope’s (27002L Karl Storz, Rietheim-Weilheim, Germany) working channel that allowed retrograde ureteral access with relative ease. A gentle attempt was made for uretero- scopic access between these two guidewires. This maneu- ver allowed the optical ureteral dilation, permitting an eas- ier upper tract access as well as inspection for the presence of pathology such as stones, strictures, or tumors, offering the possibility of treatment along all the ureter and, often, also in the kidney. At the same time, ureteral compliance and caliber were assessed in order to select the proper UAS size, avoiding ureteral injuries. The ureteroscope was withdraw and the UAS 12\14 Fr 35 cm (Flexor, Cook Urological, Spencer, IN) was introduced gently into the ureter under fluoroscopic control, by gliding over the working guidewire. In patients with ureteral stent, a PTFE guidewire 0.035/145 cm (Cook Urological, Spencer, IN) was inserted and advanced to the kidney through the distal end of the stent which had been brought to the urethral meatus. Finally the inner UAS obturator with the guidewire was removed and the 7Fr\43 cm Storz semi- rigid, or flexible or digital ureteroscope (27000L, Flex-X2 or, Flex- XC Karl Storz, Rietheim-Weilheim, Germany) was inserted to complete the operation with a Holmium or Thulium Iaser device (15). We selected 12\14Fr as the best UAS size because it can accept all the flexible and some semirigid ureteroscopes, while maintaining a good drainage in order to keep low intrarenal pressures. In dif- ficult cases, when the ureter didn’t accept the larger UAS, first we tried to remove the safety guide wire with the pur- pose to get more room. If still the passage of the larger UAS was not easy, we used a smaller UAS (11\13Fr Flexor, Cook Urological, Spencer, IN). If this attempt was also with- out success, we then tried to introduce the flexible or dig- ital scope, with or without the safety guidewire, under visual or fluoroscopic control. If again this attempt was encountered with resistance, we stopped the procedure, put a DJ stent and tried the week after. If the patient was not planned for RIRS, but presented with an impacted ureteral stone with hydronephrosis, we still inserted an access sheath just below the stone and we performed a lasertripsy of the stone with a semirigid scope 9.5Fr inside the access sheath with a safety guidewire 3Fr aside, in order to have a continuous flow with gravity irrigation and still low retro-pulsion pres- sures and expulsion of fragments retrieval through the sheath. The primary outcome was the assessment of the ureteral compliance to identify a potential difficult ureter. A com- pliant ureter was defined as a ureter ≥ 14Fr if accepted easily the passage of a semirigid scope 9.5Fr with a safe- ty guidewire 3Fr aside. Patient’s data collected, included age, gender, side, hydronephrosis, stone location (renal, ureteral, renal & ureteral), UTUC, presence of ureteral strictures, an indwelling ureteral stent, previous RIRS, and previous stone elimination history. Statistical analyses The significance of possible factors affecting ureteral compliance was analyzed. Statistical analysis was per- formed with SPSS 20 adopting the chi-square test for nominal variables and the Mann-Whitney U test for con- tinuous variables. Statistical significance was considered at p < 0.05. results The study group included 100 consecutive patients that were treated at ‘Cristo Re’ Hospital in Rome. Patient’s data are presented in Table 1. 82% and 18% of the patients were submitted to RIRS and sURS respectively, with or without use of UAS. Hydronephrosis was present in 56% of the patients while in 29% a DJ stent was inserted before (24 patients) and during surgery (5 patients) due to acute obstruction, insistent pain, fever, pus, ureteral injury, ureteral stric- ture and non compliant ureter. A compliant ureter with a diameter ≥ 14Fr was present in 77 patients because a 12/14Fr UAS was inserted gently with or without a safety guidewire, either a 9.5Fr semi- rigid ureteroscope with a safety guidewire was used (objective evaluation). In 23 patients, the ureter was non Table 1. Patient demographics. Patient, n 100 Mean age years (range) 54 (16-89) Men 72 Women 28 Ureteral stone 18 Renal stone 45 Ureteral & Renal Stone 12 UTUC, hematuria 22 Ureteral stricture 23 Side right/left 51/49 Hydronephrosis (%) 56 Indwelling Double-J stent, n(%) 29 Previous RIRS, n(%) 29 Previous stone elimination, n(%) 42 Archivio Italiano di Urologia e Andrologia 2018; 90, 1 I. Boulalas, M. De Dominicis, L. Defidio 22 compliant with a diameter < 14Fr due to insertion of either a 11/13Fr UAS after removal of the safety guidewire, or of a 7Fr semirigid or flexible or digital ureteroscope with or without safety guidewire (Table 2). In 7 patients, we had to stop the procedure and a DJ stent or nephros- tomy tube was introduced. Complications were noted in 10 patients. Guidewire-induced ureteral damage occurred in 8 patients with grade I lesions, while UAS- induced ureteral injuries occurred in 2 patients with grade I lesion in one case and grade III in the other according to the endoscopic grading system (16) (Table 3). Different factors that may influence the ureteral compli- ance were examined. The following parameters correlat- ed statistically with a ureter ≤ 14F: ureteral lithiasis, ureteral stricture, unsuccessful procedures and compli- cations (Table 4). dIscussIon Over the last decade the advancements in technology and digital optics have led to an increasing role of fURS in the treatment of upper urinary tract pathology. A ureteral access sheath is an important tool during RIRS, because it lowers intra-renal pressure, facilitates ureteral re-entry, decreases costs, reduces operative time, and improves flexible uretero-renoscope longevity (17). There are different UAS’s in the market with different characteristics, sizes and lengths. Factors that are impor- tant in clinical application include a lubricated outer coating to facilitate entry, a lower friction inner coating for easy uretero-renoscope insertion, and a reinforced wall to decrease sheath kinking and bulking (18). The standard UAS has an external diameter of 14Fr, which is larger than the median 9Fr to 10Fr diameter of non stented ureters, as evaluated on imaging studies (19). Insertion of a UAS depends on the ureter status and on its anatomic variants. Failure rates of primary access due to difficult impassable ureter range from 8%-10% (20, 21). Lallas et al. in animal models showed that the over dis- tention created by the UAS caused a transient decrease in ureteral blood flow which restored at a basal level by the compensatory mechanisms of the ureteral wall and the integrity of the ureter was preserved. However, care must be taken for selecting an appropriate-size sheath and the duration of surgery should not be long because the risk of stricture development has not been clearly put for- ward (22). Viers et al. examined the association between clinic-radi- ographic features and need for pre-stenting due to inabil- ity of the ureter to accommodate the ureteroscope or the UAS, and found 17% incidence of primary upper tract access failure. Prior ipsilateral ureteral surgery and stent- ing were protective whereas < 50% ureteral opacification was associated with an increased risk of access failure (23). Some authors position the UAS under fluoroscopic guid- ance with the application of reasonable strength on the working guidewire without the performance of semi-rigid ureteroscopy (23) whereas others calibrate the ureter with an 8F/10F coaxial dilator (Boston Scientific) (24). Additional strategies, that are used to go into the ureter, include routine stent placement before RIRS which entails two-stage procedure, sequential ureteral dilators or balloon dilation with sig- nificant risk of ureteral injury (25). In a prospective study in 248 patients undergoing sURS and fURS Mogilevkin et al. found that in 22% of patients the UAS was not easily passed. Factors of successful insertion were: older age, presenting and previous same-side ureteroscopy (25). Traxer and Thomas, in a two center prospective review, collected data on 359 patients who received a 12/14Fr UAS before a RIRS for renal stones. The authors identified and classified any ureteral injuries. UAS-induced ureteral lesions occurred in 46.5% of patients, with com- plete wall perforation in 13.4%. Table 4. Parameters of compliant ureter. compliant ≥ 14Fr non compliant < 14Fr p-value 77 pts 23 pts Age 57.6 52.1 0.1 Sex (males) 53 (69%) 19 (83%) 0.4 Ureteral lithiasis 13 (17%) 14 (61%) < 0.001 Pre-stenting 28 (36%) 1 (4%) < 0.002 Hydronephrosis 39 (51%) 17 (74%) 0.1 First time RIRS 47 (61%) 15 (65&) 1 Previous RIRS 26 (34%) 3 (13%) 0.000 Number of patients with 22 (28%) 4 (17%) 0.6 renal stones ≤ 1.5 cm (%) Number of patients with 2 (2.6%) 2 (8.6%) 1 ureteral stones ≤ 1 cm (%) UTUC 18 (23%) 4 (17%) 0.5 Ureteral stricture 1 (1.3%) 22 (95%) < 0.05 Previous stone elimination 29 (38%) 11 (49%) 0.004 Unsuccessful procedures 0 7 (30%) < 0.005 Complications 5 (6.5%) 5 (21%) < 0.01 Table 3. Complications. Patient 10 Patients, grade Guidewire 8 8 Grade I uas 2 1 Grade I 1 Grade III Table 2. Results of ureteral calibration. Patients ureter diameter 77 ≥ 14fr Gently passage of a 12/14Fr UAS with or without a safety guidewire 73 ≥ 14fr Gently passage of a 9.5 Semirigid Ureteroscope with a safety guidewire 4 ≥ 14fr Patients ureter diameter 23 < 14fr Gently passage of a 11/13F UAS after removal of the safety guidewire 1 < 14fr Gently passage of a 7Fr Semirigid, flexible or or digital Uretero-renoscope with or without a safety guidewire 22 < 14fr 23Archivio Italiano di Urologia e Andrologia 2018; 90, 1 Semirigid ureteroscopy prior RIRS The authors conclude that is imperative to visualize the ureter at the end of the procedure and that pre-stenting can reduce the risk of severe injury to the ureter. Risk factors for high grade lesions included age, male gender, and lack of preoperative stent (26). However, in another work on 2239 patients treated with fURS from the Clinical Research Office of the Endourological Society (CROES), Traxer et al. reported that UAS usage did not increase the risk of ureteral wall damage (27). Guzelburc et al. in a prospective study investigated ureteral injuries by placing two different UAS (9.5/11.5Fr-12/14Fr) during retrograde intrarenal sur- gery (RIRS) for renal stones. The researchers identified 41,6% ureteral lesions, with deep tear of the mucosal and submucosal layer in 2.97% (PULS grade 2) of patients and no injuries of grade 3+. PULS grade 2 patients were all males and a DJ stent was placed pre- operatively in all cases (28, 29). Yet, there have been few studies demonstrating signifi- cant long-term ureteral damage following the use of a UAS. In the past, one ureteropelvic junction stricture (1.4%) was noted to occur during a mean follow-up of 11 months after UAS use (30). In our study 77% of the patients had a compliant ureter ≥ 14Fr, and 23 a not compliant ureter < 14Fr. Age, sex, stone size, hydronephrosis, or UTUC had no influence on ureteral compliance in this analysis. Patients with an indwelling DJ stent, previous RIRS his- tory and previous stone elimination accommodated eas- ily a 12/14Fr UAS. The presence of ureteral stone adversely affected compli- ance due to acute or chronic inflammation. The ureteral stricture caused by impacted stones, recur- rences, or conservative treatment of UTUC’s were also consistent with a non compliant ureter < 14Fr. Finally the unsuccessful procedures and the complica- tions were correlated with a not compliant ureter. The overall low incidence of unsuccessful procedures (7%) is due to the adoption of some tricks before inter- rupting the procedure, such as the removal of safety guidewire or the use of a smaller UAS or ureteroscope. Only in 8 patients complications were caused by the guidewire and only in 2 by the UAS, of which only one had a grade 3 lesion. The low complications rate (10%), most of them of grade I, is probably due to the respect of the two fundamental endourological rules: the first one is to adapt the instru- ment\device to the ureter and not the ureter to the instrument, and the second one is to never force in the introduction or extraction of instrument or device. In the current study the importance of our technique to perform sURS prior to UAS insertion during RIRS is demonstrated, as it permits ureteral inspection and allows assessment of ureteral compliance. Those with a low likelihood for effective 12/14Fr UAS include patients with ureteral stricture and ureteral stone. However, this study presents some limitations due to the small number of patients. Probably the data can be dif- ferent in a larger cohort of patients. Also, we didn’t have a follow-up of patients to report possible postoperative complications. conclusIons Semirigid ureteroscopy performed prior retrograde intrarenal surgery (RIRS) is an outstanding tool for evalu- ation of ureteral compliance, allowing selection of the correct UAS size. A compliant ureter ≥ 14Fr was found in 3/4 of the patients. Parameters of successful insertion of a 12/14Fr UAS were an indwelling DJ stent, and a his- tory of previous RIRS or stone elimination while the presence of a ureteral stone or stricture, unsuccessful procedures and complications significantly predicted a non compliant ureter < 14Fr. reFerences 1. Oberlin DT, Flum AS, Bachrach L, et al. Contemporary surgical trends in the management of upper tract calculi. J Urol. 2015; 193:880. 2. Patel A, Fuchs GJ. Expanding the horizons of SWL through adjunctive use of retrograde intrarenal surgery: New techniques and indications. J Endourol. 1997; 11:33. 3. Shin R, Lipkin M, Preminger G. 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Urology. 2003; 61:518. Correspondence Boulalas Ioannis, MD, PhD (Corresponding Author) iboulalas@yahoo.gr De Dominicis Mauro, MD dedominicism@alice.it Defidio Lorenzo, MD defidio@tin.it Department of Urology - Cristo Re Hospital Via delle Calasanziane 25, 00167 Rome, Italy