EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 available at www.sciencedirect.com journal homepage: www.eu-openscience.europeanurology.com Stone Disease Improving Outcomes of Same-sitting Bilateral Flexible Ureteroscopy for Renal Stones in Real-world Practice—Lessons Learnt from Global Multicenter Experience of 1250 Patients Daniele Castellani a,*, Olivier Traxer b, Deepak Ragoori c, Andrea Benedetto Galosi a, Virgilio De Stefano a, Nariman Gadzhiev d, Yiloren Tanidir e, Takaaki Inoue f, Esteban Emiliani g, Saeed Bin Hamri h, Mohamed Amine Lakmichi i, Chandra Mohan Vaddi j, Chin Tiong Heng k, Boyke Soebhali l, Sumit More m, Vikram Sridharan n, Mehmet Ilker Gökce o, Azimdjon N. Tursunkulov p, Arvind Ganpule q, Giacomo Maria Pirola r, Angelo Naselli r, Cemil Aydin s, Fernando Ramón de Fata Chillón t, Catalina Solano Mendoza b,u, Luigi Candela b,v, Ben Hall Chew w, Bhaskar Kumar Somani x, Vineet Gauhar k a Urology Unit, Azienda Ospedaliero-Universitaria delle Marche, Università Politecnica delle Marche, Ancona, Italy; b Department of Urology AP-HP, Sorbonne University, Tenon Hospital, Paris, France; c Department of Urology, Asian Institute of Nephrology & Urology, Irram Manzil Colony, Hyderabad, Telangana, India; d Department of Urology, Saint-Petersburg State University Hospital, Saint-Petersburg, Russia; e Department of Urology, School of Medicine, Marmara _ University, Istanbul, Turkey; f Department of Urology, Hara Genitourinary Private Hospital, Kobe University, Kobe, Japan; g Department of Urology, Fundacion Puigvert, Autónomos University of Barcelona, Barcelona, Spain; h Division of Urology, Department of Surgery, Ministry of the National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; i Department of Urology, University Hospital Mohammed the VIth of Marrakesh, Marrakesh, Morocco; j Department of Urology, Preeti Urology and Kidney Hospital, Hyderabad, India; k Department of Urology, Ng Teng Fong General Hospital, Singapore, Singapore; l Department of Urology, Abdul Wahab Sjahranie Hospital, Medical Faculty Mulawarman University, Samarinda, Indonesia; m Department of Urology, Sarvodaya Hospital and Research Centre, Faridabad, India; n Department of Urology, Sree Paduka Speciality Hospital, Thillai Nagar, India; o Department of Urology, Ankara University, School of Medicine, Ankara, Turkey; p Urology Division, AkfaMedline Hospital, Tashkent, Uzbekistan; q Department of Urology, Mulßjibhai Patel Urological Hospital, Nadiad, Gujarat, India; r Urology Department, San Giuseppe Hospital, IRCCS Multimedica, Multimedica Group, Milan, Italy; s Department of Urology, Hitit University, School of Medicine, Çorum, Turkey; t Department of Urology, Clinica Universidad de Navarra, Madrid, Spain; u Department of Endourology, Uroclin S.A.S, Medellín, Colombia; v Division of Experimental Oncology/Unit of Urology, URI-Urological Research Institute IRCCS Ospedale San Raffaele, University Vita-Salute San Raffaele, Milan, Italy; w Department of Urology, University of British Columbia, Vancouver, Canada; x Department of Urology, University Hospitals Southampton, NHS Trust, Southampton, UK Article info Abstract Article history: Background: Bilateral kidney stones are commonly treated in staged procedures. Accepted March 29, 2023 Objective: To evaluate outcomes after same-sitting bilateral retrograde intrarenal surgery (SSB-RIRS) for renal stones. Associate Editor: Design, setting, and participants: Data from adults who underwent bilateral RIRS in Silvia Proietti 21 centers were retrospectively reviewed (from January 2015 to June 2022). The inclusion criteria were unilateral/bilateral symptomatic bilateral stone(s) of any * Corresponding author. Urology Unit, Azienda Ospedaliero-Universitaria delle Marche, Università Politecnica delle Marche, Via Conca 71, 60126, Ancona, Italy. Tel. +393471814691; Fax: +39715963367. E-mail address: castellanidaniele@gmail.com (D. Castellani). https://doi.org/10.1016/j.euros.2023.03.018 2666-1683/Ó 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 52 EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 size/location in both kidneys and bilateral stones on follow-up with symptom/ stone progression. Stone-free rate (SFR) was defined as absence of any fragment Keywords: >3 mm at 3 mo. Kidney calculi Outcome measurements and statistical analysis: Continuous variables are presented as Flexible ureteroscopy medians and 25–75th percentiles. A multivariable logistic regression analysis was Lithotripsy performed to evaluate independent predictors of sepsis and bilateral SFR. Laser Results and limitations: A total of 1250 patients were included. The median age was Retrograde intrarenal surgery 48.0 (36–61) yr. Of the patients, 58.2% were prestented. The median stone diameter Holmium laser was 10 mm on both sides. Multiple stones were present in 45.3% and 47.9% of the Thulium fiber laser left and right kidneys, respectively. Surgery was stopped in 6.8% of cases. The med- ian surgical time was 75.0 (55–90) min. Complications were transient fever (10.7%), fever/infection needing prolonged stay (5.5%), sepsis (2%), and blood transfusion (1.3%). Bilateral and unilateral SFRs were 73.0% and 17.4%, respectively. Female (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.18–7.49, p = 0.02), no antibiotic prophylaxis (OR 5.99, 95% CI 2.28–15.73, p < 0.001), kidney anomalies (OR 5.91, 95% CI 1.96–17.94, p < 0.001), surgical time 100 min (OR 2.86, 95% CI 1.12– 7.31, p = 0.03) were factors associated with sepsis. Female (OR 1.88, 95% CI 1.35– 2.62, p < 0.001), bilateral prestenting (OR 2.16, 95% CI 1.16–7.66, p = 0.04), and the use of high-power holmium:YAG laser (OR 1.63, 95% CI 1.14–2.34, p < 0.01) and thulium fiber laser (OR 2.50, 95% CI 1.32–4.74, p < 0.01) were predictors of bilateral SFR. Limitations were retrospective study and no cost analysis. Conclusions: SSB-RIRS is an effective treatment with an acceptable complication rate in selected patients with kidney stones. Patient summary: In this large multicenter study, we looked at outcomes after same-sitting bilateral retrograde intrarenal surgery (SSB-RIRS) for renal stones in a large cohort. We found that SSB-RIRS was associated with acceptable morbidity and good stone clearance after a single session. Ó 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative- commons.org/licenses/by-nc-nd/4.0/). 1. Introduction 2. Patients and methods As a part of the Team of Worldwide Endourological Researchers of the The incidence of nephrolithiasis has increased in the last Endourological Society, a retrospective analysis of all consecutive two decades, with a prevalence ranging from 7% to 13% in patients who had SSB-RIRS for renal stones between January 2015 and North America, 1% to 5% in Asia, and 5% to 9% in Europe June 2022 in 21 centers was performed. Consultant surgeons involved [1]. Boyce et al [2] found that the prevalence of kidney stone in this study had RIRS experience of performing >100 procedures. The disease was 1.7% in a large series of asymptomatic patients, inclusion criteria were age 18 yr, bilateral stones of any size and loca- with 10% of them having bilateral stones. Up to a third of tion in the kidneys diagnosed due to unilateral or bilateral symptomatic asymptomatic stones ultimately require intervention [3], presentation, and patients with bilateral renal stones who were on and patients with bilateral stones are at a high risk for follow-up and noted to have stone or symptom progression. The exclu- recurrence and surgical intervention [4]. Traditionally, sion criteria were concomitant ureteral lithotripsy, stone located in a bilateral kidney stones have been treated in staged proce- calyceal diverticulum, in-tandem procedure, and RIRS done as a com- dures because of concerns regarding the safety of perform- bined procedure for endoscopic combined intrarenal surgery. Stone size ing same-session bilateral surgery. Nevertheless, the was calculated as the largest diameter. In the case of multiple stones, potential advantages of bilateral simultaneous procedures data from the largest stone were reported. Antiplatelets/anticoagulants rely on single anesthesia, less utilization of disposable were stopped 3–7 d before surgery and resumed as per each center’s dis- devices, reduced surgical time and cumulative hospital stay, cretion. Antibiotic prophylaxis was given in each center with a single on- and fewer working day loss with subsequent lower overall table dose chosen as per the local pathogen prevalence and antibiotic susceptibility profiles. Lithotripsy was carried out either by holmium: cost. In this scenario, retrograde intrarenal surgery (RIRS) YAG laser (HL) or by thulium fiber laser (TFL). RIRS was performed as is an appealing procedure due to its wide adoption [5], per the current standard technique [12]. We collected the number of low morbidity [6], and excellent stone-free rate (SFR) [5]. procedures that were ended before complete bilateral lithotripsy and However, only a few small, mainly single-center series the reasons behind their abortion. The decision to abandon surgery studies reported the outcomes of same-sitting bilateral was individualized by each surgeon’s own previous experience. Surgical RIRS (SSB-RIRS) with disparity between the inferences time was estimated from the start of cystoscopy to the placement of a [7–11]. bladder catheter. Sepsis was defined as ‘‘life-threatening organ dysfunc- This study aimed to assess the outcomes of SSB-RIRS in a tion caused by a dysregulated host response to infection’’ [13]. SFR was large, real-life series of patients with kidney stones. assessed 3 mo after surgery according to the local standard of care with EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 53 Table 1 – Patient baseline characteristics Table 1 (continued) N = 1250 N = 1250 Age (yr), median (25–75th percentile) 48.0 (36.0–61.0) Upper pole 245 (19.6) Males, n (%) 844 (67.5) Middle pole 313 (25.0) Ethnicity, n (%) Lower pole 342 (27.4) Indian 319 (25.5) Pelvis 350 (28.0) Caucasian 105 (8.4) ASA = American Society of Anesthesiologists; CT = computed tomography; Middle East 117 (9.4) HU = Hounsfield units. Russian 93 (7.4) a Failure to access: failure to access the renal pelvis with ureteral North African 24 (1.9) access sheath due to a noncompliant ureter. Routine practice: stent Asian 561 (44.9) insertion to allow passive ureteral dilatation before elective surgery. Turkish 31 (2.5) Symptomatic: relief of pain with delayed surgery. Emergency stent- Body mass index, median (25–75th percentile) 26.5 (23.0–30.0) ing: stent insertion due to acute renal failure/infection with delayed Comorbidity, n (%) surgery. Diabetes 178 (14.2) Hypertension 373 (29.8) On antiplatelet/anticoagulation drugs 179 (14.3) Ischemic heart disease 159 (12.7) Spinal deformity 35 (2.8) Chronic kidney disease 136 (10.9) kidney, ureter, and bladder x-ray and/or ultrasound or noncontrast com- ASA score, n (%) puted tomography (CT), and was defined as absence of any residual frag- 1 600 (48.0) ment (RF) >3 mm. The study approval by the institutional review board 2 496 (39.7) was obtained from the Asian Institute of Nephrology and Urology (AINU 3 153 (12.2) 4 1 (0.1) #13/2022). Each center provided anonymized data and had approval Symptoms at presentation, n (%) from their institutional review board if deemed necessary. Hematuria only 147 (11.8) Pain 748 (59.8) Hematuria and pain 281 (22.5) 2.1. Statistical analysis Asymptomatic 74 (5.9) Side of pain (n = 1029) Categorical data are presented as absolute numbers and percentages, Right 309 (30.0) and continuous data as medians and (25–75th percentiles). A univariate Left 296 (28.9) Bilateral 424 (41.1) logistic regression analysis was performed to assess factors associated Emergency presentation due to ureteric stone, n (%) 225 (18) with sepsis and bilateral SFR. Variables significantly associated with sep- Recurrent stone formers, n (%) 578 (46.2) sis and SFR were analyzed in a multivariable logistic regression model. Positive urine culture at presentation, n (%) 523 (41.8) Prestented, n (%) Data are presented as odds ratio (OR) and 95% confidence interval (CI). No 523 (41.8) Statistical significance was set at two-tailed p < 0.05. All statistical tests Unilaterally 456 (36.5) were performed using the SPSS software package version 25.0 (IBM Bilaterally 271 (21.7) Corp., Armonk, NY, USA). Reason for prestenting (n = 727) a, n (%) Failure to access 184 (25.3) Routine practice 234 (32.2) Symptomatic 207 (28.5) 3. Results Emergency stenting 102 (14.0) Prestenting days (n = 727), n (%) <14 282 (38.8) During the study period, 1250 patients met the inclusion 14 445 (61.2) criteria. Table 1 shows patient baseline characteristics. Preoperative tamsulosin, n (%) 467 (37.4) Preoperative imaging modality, n (%) There were 844 (67.5%) males. The median age was 48.0 Noncontrast CT 1090 (87.2) (36–61) yr. Pain was the most common symptom at presen- Contrast CT 132 (10.6) tation (59.8%), followed by hematuria and pain (22.5%). Combination of x-ray and ultrasound 28 (2.2) Kidney/collecting system anatomy, n (%) Almost half of the patients were recurrent stone formers Bilateral normal 1183 (94.7) (46.2%). Of the patients, 58.2% were prestented, with rou- Unilateral malrotated 24 (1.9) tine practice (32.2%) as the main. The median stone diame- Horseshoe kidney 19 (1.5) Unilateral duplex collecting system 19 (1.5) ter was 10 mm on both sides, and the pelvis was the most Unilateral ectopic kidney 5 (0.4) common stone location in both kidneys. Multiple stones Left kidney were present in 45.3% and 47.9% of the left and right kid- Stone diameter (mm), median (25–75th percentile) 10.0 (8.0–13.0) HU, median (25–75th percentile) 1050 (800–1300) neys, respectively. Multiple stones, n (%) 566 (45.3) Table 2 displays intraoperative outcomes. Antibiotic pro- Stone location, n (%) phylaxis was administered in 84% of cases; 89.4% of patients Upper pole 222 (17.8) Middle pole 304 (24.3) had bilateral surgery under general anesthesia. Only 98 Lower pole 347 (27.8) cases (7.8%) were performed sheathless. A ureteral access Pelvis 377 (30.1) sheath (UAS) was employed bilaterally in most of the cases Right kidney Stone diameter (mm), median (25–75th percentile) 10 (7.8–13.0) (72.6%). A reusable ureteroscope was used in 56.9% of cases. HU, median (25–75th percentile) 1010 (800–1286) Low-power HL was used in 41.4% of cases, followed by Multiple stones, n (%) 599 (47.9) high-power HL (33.2%) and TFL (24.4%). A combination of Stone location, n (%) techniques was the most common lithotripsy mode (71%). Surgery was stopped in only 85 (6.8%) cases, and the most 54 EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 Table 2 – Intraoperative outcomes Table 2 (continued) N = 1250 N = 1250 Preoperative antibiotics given for, n (%) Reasons to stop surgery (n = 85) b Urinary tract infection 137 (11.0) Anesthesia issue 16 (18.8) Prophylaxis 1050 (84.0) Prolonged operation time 50 (58.8) No antibiotics 63 (5.0) Scope breakdown 3 (3.5) Anesthesia, n (%) Surgeon decision 68 (80.0) General 1118 (89.4) Stone volume deemed too big 29 (34.2) Gated 402 (36.0) Concern for sepsis 37 (43.5) Apneic 273 (24.4) Total fluoroscopy time (s), median (25–75th 78.0 (48.0–120.0) None 443 (39.6) percentile) Spinal 132 (10.6) Lasing time (min), median (25–75th percentile) 36.0 (30.0–50.0) Semirigid ureteroscopy before RIRS, n (%) 1008 (80.6) Total surgical time (min), median (25–75th 75.0 (55.0–90.0) Patient position, n (%) percentile) Split leg 20 (1.6) On-table estimated SFR, n (%) 801 (64.1) Lithotomic 1230 (94.8) RIRS = retrograde intrarenal surgery; SFR = stone-free rate; UAS = ureteral Surgeon position, n (%) access sheath. Sitting 825 (66.0) a Combination of two or three modes. Standing 384 (30.7) b More than one choice possible. Missing 41 (3.3) Multiple surgeons involved in the procedure, n (%) 204 (16.3) Procedure done by, n (%) Consultant 1031 (82.5) Trainer 22 (1.8) reported reason was prolonged operation time (58.8%) fol- Both 197 (15.8) lowed by concern for sepsis (43.5%). Most patients had a UAS, French (outer diameter), n (%) stent positioned after RIRS (97.3%, bilaterally in 58.4% of Sheath less 98 (7.8) 10 224 (17.9) patients). The median fluoroscopic time was 78.0 (48– 10.5 223 (17.8) 120) s. The median surgical time was 75.0 (55–90) mi (90 12 372 (29.8) [62–125] min in those patients who had their surgery 13 108 (8.6) 14 116 (9.3) stopped vs 74 [55–90] min in those whose surgery was Missing 109 (8.8) completed bilaterally). Suction UAS, n (%) 171 (13.7) Regarding early postoperative complications (Table 3), Bilateral UAS (n = 1152), n (%) 836 (72.6) Same UAS (n = 1152), n (%) 947 (82.2) 134 (10.7%) patients had fever lasting up to 24 h (Clavien Type of ureteroscopes, n (%) 1), 69 (5.5%) had fever/infection needing prolonged stay Single use 539 (43.1) (Clavien 2), 25 (2%) had sepsis requiring intensive care Reusable 711 (56.9) Size of ureteroscope tip, French, n (%) admission (Clavien 4b), and 16 (1.3%) required a blood 7.5 588 (47.0) transfusion (Clavien 2). The median hospital stay was 2 7.6 18 (1.4) (1–2) d, and 241 (14.3%) patients were discharged within 7.7 398 (31.8) 8.0 10 (0.8) 24 h of surgery. 8.4 5 (0.4) At 3-mo follow-up, bilateral SFR was 73.0%, whereas uni- 8.5 102 (8.2) lateral SFR was 17.4%. Among 338 patients with RF, 189 8.6 14 (1.1) 9.0 3 (0.2) (55.9%) were deemed suitable for observation only. RIRS 9.5 104 (8.3) was the most preferred option in those requiring further Missing 8 (0.6) treatment (37%). Scope breakage needing change, n (%) 20 (1.6) Type of laser, n (%) Female (OR 2.97, 95% CI 1.18–7.49, p = 0.02), no antibi- Holmium laser 30 W 517 (41.4) otic prophylaxis (OR 5.99, 95% CI 2.28–15.73, p < 0.001), Holmium laser >30 W 415 (33.2) kidney anomalies (OR 5.91, 95% CI 1.96–17.94, p < 0.001), Thulium fiber laser 318 (25.4) MOSES technology 151 (12.1) and surgical time 100 min (OR 2.86, 95% CI 1.12–7.31, Lithotripsy mode, n (%) p = 0.03) were factors associated with sepsis at the multi- Dusting 439 (35.1) Fragmentation 232 (18.6) variable analysis (Table 4). Female (OR 1.88, 95% CI 1.35– Pop corning 195 (15.6) 2.62, p < 0.001), bilateral prestenting (OR 2.16, 95% CI Combination a 888 (71.0) 1.16–7.66, p = 0.04), and the use of high-power HL (OR Fragment extraction by basket, n (%) 566 (45.3) Postoperative stent positioning, n (%) 1216 (97.3) 1.63, 95% CI 1.14–2.34, p < 0.01) and TFL (OR 2.50, 95% CI Bilaterally (n = 1216) 710 (58.4) 1.32–4.74, p < 0.01) were predictors of bilateral SFR at the Reasons for postoperative stent positioning (n = multivariable analysis (Table 5), whereas age (OR 0.98, 1216), n (%) Routine practice 1078 (86.2) 95% CI 0.97–0.99, p < 0.001), stone size (OR 0.94, 95% CI Possible reintervention 124 (9.9) 0.93–0.98, p < 0.01 in the left kidney; OR 0.96, 95% CI Ureteric injury 32 (2.6) 0.94–0.99, p < 0.01 in the right kidney), and surgical time Missing 34 (2.7) Intraoperative complications, n (%) 100 min (OR 0.38, 95% CI 0.26–0.58, p < 0.001) were less Pelvicalyceal system injury 16 (1.3), bilateral in likely associated with bilateral SFR. 11 Ureteric injury 32 (2.6) Bilateral injury 1 (0.08) 4. Discussion Traxer grade 1 20 (1.6) Traxer grade 2 12 (0.9) Need to stop surgery, n (%) 85 (6.8) Bilateral renal stones pose a unique challenge for patients and surgeons alike, and while there are no guidelines on EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 55 Table 3 – Postoperative outcomes bilateral in 41.1%. Traditional teaching advocates renal N = 1250 stone intervention for symptomatic patients and possible 30-d postoperative complications, n (%) observation for the asymptomatic side. For patients with Fever >38°C lasting up to 24 h 134 (10.7) asymptomatic stones, in certain situations intervention Fever/infection needing prolonged stay 69 (5.5) may be approached. Despite RIRS having a good track Sepsis requiring ICU admission 25 (2.0) Hematuria with dropped hemoglobin 90 (7.2) record of being a safe and effective minimally invasive Blood transfusion 16 (1.3) intervention [5], many surgeons hesitate to perform bilat- Stone analysis (n = 1045) a, n (%) eral RIRS as theoretically it can double the complications Calcium oxalate monohydrate 479 (45.8) Calcium oxalate dihydrate 311 (29.8) and may not give the desired SFR [7]. Uric acid 109 (10.5) Nevertheless, treating both sides is also advisable in Struvite 90 (8.6) patients with a concurrent asymptomatic contralateral Cystine 19 (1.8) Carbonate calcium phosphate 14 (1.3) stone, given that it is done under the same anesthesia as a Hydroxyapatite 13 (1.2) single-session procedure. Indeed, Li et al [16] demonstrated Brushite 5 (0.5) that patients with contralateral stones >6 mm were more Mixed 5 (0.5) Hospital stay (<24 h), n (%) 241 (14.3) likely to require forthcoming surgery than those treated Hospital stay (d), median (25–75th percentile) 2 (1–2) bilaterally. Geraghty et al [3] showed that evidence for Post-RIRS imaging within 48 h, n (%) 763 (61.0) bilateral simultaneous endourological procedures is limited, Noncontrast CT 102 (13.4) X-ray 381 (49.8) but results showed that outcomes are at least equivalent to Ultrasound 263 (34.5) staged procedures. The key advantages seem to be reduced Combination of x-ray and ultrasound 17 (2.3) operative time, cost, and hospital stay. Perhaps our study Post-RIRS imaging at 3 mo, n (%) 1206 (96.5) Noncontrast CT 612 (50.8) reflects this trend of offering upfront intervention in asymp- X-ray 292 (24.2) tomatic and symptomatic sides with RIRS under one anes- Ultrasound 168 (13.9) thesia to benefit the patient and prevent the need for Combination of x-ray and ultrasound 134 (11.1) RF single >3 mm, n (%) subsequent intervention. Unilateral 132 (10.6) On the contrary, one can argue that the complication rate Bilateral 52 (4.2) might be higher after SSB-RIRS compared with unilateral/ Multiple RF any size, n (%) Unilateral 86 (6.9) staged procedures. Danilovic et al [7] compared the out- Bilateral 92 (7.4) comes of SSB-RIRS with unilateral procedures and found SFR, n (%) that the former had significantly more overall complica- Unilateral 218 (17.4) Bilateral 912 (73.0) tions (15.9% vs 39.9%) and emergency room admissions Bilateral non–stone free 120 (9.6) (11.6% vs 34.8%) than the latter. However, that study was Post-RIRS procedures for RF (n = 338), n (%) biased by the fact that bilateral surgery was compared with ESWL 18 (5.3) RIRS 125 (37.0) single-side-only procedures and not with the number of PCNL 1 (0.3) renal units treated. In fact, the risk of complications is dis- ECIRS 5 (1.5) tributed over time in staged treatment than being encoun- Observe 189 (55.9) tered at once in SSB-RIRS [17]. Peng et al [8] matched CT = computed tomography; ECIRS = endoscopic combined intrarenal surgery; ESWL = extracorporeal shock wave lithotripsy; ICU = intensive bilateral with unilateral RIRS based on overall renal units care unit; PCNL = percutaneous nephrolithotomy; RF = residual frag- and demonstrated that the complication rate did not differ ments; RIRS = retrograde intrarenal surgery; SFR = stone-free rate. significantly. a Number of stones analyzed. Among RIRS complications, sepsis is undoubtedly the most dreadful one, being associated with extended hospi- talization, intensive care unit admission, and even death. In our series, the incidence of sepsis was 2%, and this was in line with a recent review that found its incidence to range the best approach, in recent times RIRS has made the man- from 0.5% to 11% in unilateral surgery [18]. We found that agement of these stones more accessible. In fact, current women were at an almost three-fold higher risk of sepsis, endourological intervention for kidney stone disease is so and this should be acknowledged when one counsels advanced that endoscopic combined intrarenal surgery patients before a planned SSB-RIRS. and simultaneous bilateral endoscopic surgery are now con- The presence of kidney anomalies was found to be sidered the forerunners for a tailored and personalized another sepsis risk factor in our series. This is perhaps approach in managing such patients [14,15]. However, related to renal/collecting system anatomy, which often large-volume multicenter real-world data are lacking on results in compromised urine drainage and increases the how bilateral surgical intervention by RIRS impacts SFR risk of developing urinary tract infections. A previous study and surgical complications. This study highlights the pre-, by García Rojo et al [19] showed that the incidence of post- intra-, and postoperative nuances; considerations; and out- RIRS sepsis in anomalous kidneys was 10.1%, confirming comes of SSB-RIRS from a global perspective. that renal/collecting system anomalies are more prone to First, the indication for bilateral surgery should be eval- infections. Patients with anomalous kidneys were not uated. Almost all patients included in our analysis were excluded from our analysis if they had bilateral RIRS, as ours symptomatic at presentation (95.1%), and most of them pre- was a real-life study and we were interested in evaluating sented with pain (82.3%). Among the latter, the pain was the outcomes in such a case. Indeed, RIRS showed to be safe 56 EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 Table 4 – Univariable and multivariable analysis of factors affecting sepsis Univariable analysis Multivariable analysis OR (95% CI) p value OR (95% CI) p value Age 1.01 (0.98–1.03) 0.7 – Female 2.71 (1.22–6.0) 0.01 2.97 (1.18–7.49) 0.02 ASA score 1.37 (0.80–2.36) 0.26 – Body mass index 0.94 (0.71–1.24) 0.63 – Diabetes 1.15 (0.39–3.39) 0.80 – Chronic kidney disease 1.4 (0.47–4.14) 0.54 – Positive urine culture 2.12 (0.94–4.75) 0.69 – Prestenting No prestenting 0.56 (0.07–4.67) 0.59 Unilateral 1.76 (0.66–4.74) 0.26 Bilateral 1.48 (0.47–4.62) 0.51 – Antibiotics (ref. prophylaxis) Treating urinary tract infections 2.42 (0.54–10.92) 0.25 – No antibiotics 5.2 (2.21–12.26) <0.001 5.99 (2.28–15.73) <0.001 Kidney anomalies (ref. normal bilateral kidneys) 4.70 (1.71–12.91) <0.01 5.91 (1.96-17.94) <0.01 Recurrent stone formers 1.27 (0.57–2.80) 0.56 Left kidney stone size 1.05 (0.98–1.14) 0.14 – Left kidney Hounsfield units 1.00 (0.99–1.01) 0.2 – Multiple left kidney stone 1.81 (0.81–4.06) 0.15 – Right kidney stone size 1.02 (0.95–1.10) 0.53 – Right kidney Hounsfield Units 1.00 (0.99–1.00) 0.720 – Multiple right kidney stone 1.94 (0.85–4.43) 0.16 – No ureteral access sheath 1.05 (0.23–4.32) 0.99 – Ureteral access sheath less than 12 French 0.25 (0.03–1.98) 0.12 Type of laser (ref. low power holmium) High-power holmium 0.35 (0.11–1.70) 0.07 Thulium fiber laser 0.81 (0.32–2.03) 0.65 – Lithotripsy mode (ref. pop-corning) Dusting 0.68 (0.24–1.95) 0.47 Fragmentation 0.66 (0.18–2.36) 0.52 Combination 0.94 (0.32–2.82) 0.92 – Disposable ureteroscope 1.22 (0.55–2.70) 0.62 Ureteroscope tip >8 French 1.77 (0.73–4.28) 0.21 Lasing time 1.01 (0.98–1.04) 0.42 – Surgical time 100 min (ref. <100 min) 2.95 (1.21–7.21) 0.02 2.86 (1.12–7.31) 0.03 Bilateral residual fragments 1.23 (0.29–5.27) 0.78 – Mixed stones 1.32 (0.76–3.50) 0.72 Brushite stones 0.88 (0.23–2.95) 0.89 Hydroxyapatite stones 6.34 (0.76–52.69) 0.08 Uric acid stones 0.91 (0.21–3.91) 0.88 Cystine stones 6.18 (1.35–28.31) 0.01 8.62 (0.97–32.12) 0.10 Calcium oxalate monohydrate stones 0.75 (0.32–1.76) 0.51 Calcium oxalate dihydrate stones 1.43 (0.61–3.35) 0.41 Struvite stones 1.53 (0.07–3.98) 0.54 Carbonate calcium phosphate 0.97 (0.42–3.12) 0.76 ASA = American Society of Anesthesiologists; CI = confidence interval; OR = odds ratio; ref = reference. Bold value stands for significant p value. and effective with high single-stage SFR and a low compli- operative time especially without a UAS can cause deleteri- cation rate [19]. ous complications related to persistently high intrarenal According to the current European Association of Urol- pressure, which can lead to pyelorenal backflow with the ogy guidelines, antibiotic prophylaxis should be offered to concomitant entrance of pathogens and endotoxins into all patients undergoing endourological treatment [20]. In the blood stream [23]. In our series, we employed a small- our series, patients who had no prophylaxis demonstrated diameter UAS (12 French) in 65.5% of cases and uretero- a six-fold higher risk of sepsis, undoubtedly demonstrating scopes with a small-sized tip (7.7 French) in 80.2% of the importance of prophylaxis in reducing the risk of seri- cases, which allowed a good outflow, and as a consequence, ous infective complications after SSB-RIRS. an acceptable rate of infectious complications, and a very Surgical time is another pivotal factor associated with low rate of ureteric injury. The utility of these for SSB- sepsis following RIRS [18]. Ozgor et al [21] demonstrated RIRS reflects that in modern-day RIRS practice, surgeons that RIRS lasting for >60 min was associated with a doubled preferably choose smaller-diameter scopes and UAS to min- risk of infectious complications. Yet, Sugihara et al [22] imize the possibility of any ureteric injury [24]. showed a linear positive association between operation A 100-min cutoff could be a reasonable time to reduce time and severe adverse events (OR 1.58 in 90–119 min; the risk of sepsis SSB-RIRS, and urologists should not exceed OR 4.28 in >210 min compared with 59 min) [22]. Our it to render patients stone free. As a matter of fact, in some analysis reflects that when the surgical time lasted for circumstances, we decided to stop surgery earlier due to >100 min, there was a 2.8-fold higher risk of sepsis. Longer concerns for sepsis or prolonged operation time. Therefore, EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 57 Table 5 – Univariable and multivariable analysis of factors affecting bilateral stone-free rate Univariable analysis Multivariable analysis OR (95% CI) p value OR (95% CI) p value Age 0.97 (0.96–0.98) <0.001 0.98 (0.97–0.99) <0.001 Female 0.60 (0.46–0.78) <0.001 1.88 (1.35–2.62) <0.001 Body mass index 0.94 (0.87–1.01) 0.05 – Prestenting (ref. no prestenting) Unilateral 1.61 (1.19–2.17) 0.02 1.35 (0.66–1.59) 0.51 Bilateral 9.19 (3.94–21.46) <0.001 2.16 (1.16–7.66) 0.04 Kidney anomalies (ref. normal bilateral kidneys) 0.60 (0.36–1.01) 0.05 – Recurrent stone formers 0.61 (0.47–0.78) <0.001 0.82 (0.59–1.12) 0.21 Left kidney stone size 0.93 (0.91–0.95) <0.001 0.94 (0.93–0.98) <0.01 Left kidney upper pole 0.69 (0.47–1.02) 0.06 – Left kidney middle pole 0.92 (0.66–1.27) 0.6 – Left kidney lower pole stone 1.18 (0.87–1.60) 0.28 – Left kidney renal pelvis 1.75 (1.31–2.33) <0.001 1.34 (0.91–1.01) 0.15 Left kidney Hounsfield units 1.02 (0.99–1.01) 0.05 – Multiple left kidney stones 0.56 (0.45–0.74) <0.001 1.14 (0.77–1. 70) 0.51 Right kidney stone size 0.91 (0.88–0.93) <0.001 0.96 (0.94–0.99) <0.01 Right kidney upper pole 1.31 (0.89–1.92) 0.17 – Right kidney middle pole 0.88 (0.72–1.17) 0.51 – Right kidney lower pole stone 1.02 (0.75–1.39) 0.88 – Right kidney renal pelvis 1.73 (1.29–2.33) <0.001 0.84 (0.56–1.26) 0.39 Right kidney Hounsfield units 1.03 (0.96–1.11) 0.23 – Multiple right kidney stones 0.55 (0.42–0.71) <0.001 0.88 (0.60–1.31) 0.53 No ureteral access sheath 1.05 (0.66–1.67) 0.84 – Type of laser (ref. low power holmium) High-power holmium 1.45 (1.09–1.92) 0.01 1.63 (1.14–2.34) <0.01 Thulium fiber laser 3.70 (2.55–5.38) <0.001 2.50 (1.32–4.74) <0.01 Lithotripsy mode (ref. pop-corning) Dusting 1.95 (1.48–2.46) <0.001 1.34 (0.93–1.92) 0.12 Fragmentation 0.29 (0.22–0.39) <0.001 0.37 (0.25–0.56) <0.001 Combination 1.25 (0.94–1.65) 0.13 – Disposable ureteroscope 1.06 (0.83–1.37) 0.63 – Ureteroscope tip >8 French 0.80 (0.59–1.10) 0.17 – Lasing time 0.99 (0.99–1.01) 0.53 – Total surgical time 100 min (ref. <100 min) 0.38 (0.28–0.52) <0.001 0.38 (0.26–0.58) <0.001 CI = confidence interval; OR = odds ratio; ref = reference. Bold value stands for significant p value. judicious use of the surgical time is one of the cornerstones be explained by higher success rates of UAS insertion in pre- of a safe SSB-RIRS, and in the presence of preoperative pre- stented patients [26] since the use of a UAS in flexible ure- dictors of prolonged surgical time (eg, bilateral and large teroscopy allows good irrigation and visualization, and stone burden, and anomalous kidneys), staged procedures operative efficiency [27], which may be contributory to or a simultaneous RIRS on one side and percutaneous the good SFR that we achieved. In our study, the use of nephrolithotripsy on the other side [15] should be planned TFL demonstrated a 2.5-fold odds of being bilateral stone- to minimize morbidity. free. This result can be explained in terms of both its versa- Another potential issue against SSB-RIRS is the incidence tile power setting and the ability to dust better and faster, of bilateral ureteral lesions. In our series, a ureteral injury as has been proposed in most recent studies [28]. Indeed, occurred in 2.6% of cases. A grade 2 lesion accordingly to we also found that fragmentation and stone extraction Traxer and Thomas [25] was reported in 12 patients with alone was less likely associated with bilateral SFR. only one case of bilateral grade 1 injury, and all cases had Last but not least, we found that larger stones had lower postoperative stenting only. Hence, this should not preclude bilateral SFR with higher reintervention in this subgroup. urologists from performing SSB-RIRS with a UAS. This indicates the need to caution patients beforehand the The goal of every surgical stone treatment is to render possibility of reintervention. Indeed, staged RIRS for large- the patient stone-free in a single session, which also applies volume stones has been reported as an acceptable manage- to bilateral stones. Our study demonstrated that SSB-RIRS ment choice [29]. was associated with a low incidence of patients who had This study is not devoid of limitations starting from its unilateral (17.4%) and bilateral (9.6%) RFs, and with 55.9% retrospective nature. We were not able to report all minor of patients planned for no reintervention, it showed an complications. Long-term data on ureteral strictures are excellent outcome favoring the use of SSB-RIRS as a first line unavailable, and this is another important issue to analyze. of intervention for these patients. There may be a source of bias in the analysis of SFRs since Our multivariable analysis infers that the key factors for we used different imaging modalities. SFR assessment could obtaining bilateral stone-free status were bilateral prestent- have been more robust if a postoperative CT scan was used ing and the use of high-power HL and TFL. A recent system- to verify this outcome in all patients. However, the real- atic review also showed that the SFR for RF cutoff of <1 and world usage of combinations of imaging modalities reflects <4 mm favored prestented patients [26]. This could partially a real-life practice. We should also acknowledge that from a 58 EUROPEAN UROLOGY OPEN SCIENCE 52 (2023) 51–59 patient’s perspective of inherent radiation exposure of CT Funding/Support and role of the sponsor: None. since <8% of patients undergoing CT for urolithiasis were imaged using a low-dose protocol [30]. It is also well known References that since urolithiasis can be considered a chronic condition in many patients suffering from frequent recurrence, radia- [1] Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y. Epidemiology of stone disease across the world. World J Urol tion exposure would greatly be increased if we were to rely 2017;35:1301–20. solely on CT, and this is of outmost important in patients [2] Boyce CJ, Pickhardt PJ, Lawrence EM, Kim DH, Bruce RJ. 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Re: ‘‘prospective Obtaining funding: None. evaluation of bilateral retrograde intrarenal surgery: Is it really Administrative, technical, or material support: None. safe?’’ by Danilovic et al. J Endourol 2021;35:560. Supervision: Traxer, Somani. [18] Corrales M, Sierra A, Doizi S, Traxer O. Risk of sepsis in retrograde Other: None. intrarenal surgery: a systematic review of the literature. Eur Urol Open Sci 2022;44:84–91. [19] García Rojo E, Teoh J-Y-C, Castellani D, et al. Real-world global outcomes of retrograde intrarenal surgery in anomalous kidneys: a Financial disclosures: Daniele Castellani certifies that all conflicts of high volume international multicenter study. Urology interest, including specific financial interests and relationships and affili- 2022;159:41–7. ations relevant to the subject matter or materials discussed in the manu- [20] Skolarikos A, Neisius A, Petřík A, Somani B, Thomas K, Gambaro G. script (eg, employment/affiliation, grants or funding, consultancies, EAU guidelines 2022 on urolithiasis. 2022. https:// honoraria, stock ownership or options, expert testimony, royalties, or d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU- Guidelines-on-Urolithiasis-2022_2022-03-24-142444_crip.pdf. patents filed, received, or pending), are the following: Olivier Traxer is a [21] Ozgor F, Sahan M, Cubuk A, Ortac M, Ayranci A, Sarilar O. Factors consultant for Coloplast, Rocamed, Olympus, EMS, Boston Scientific, and affecting infectious complications following flexible IPG. The remaining authors declare that they have no conflict of interest. ureterorenoscopy. Urolithiasis 2019;47:481–6. 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