ENDOUROLOGY AND STONE DISEASE A Comparison of Retrograde Intrarenal Surgery and Percutaneous Nephrolithotomy for Management of Renal Stones ≥ 2 CM Sercan Sari*1,Hakki Ugur Ozok2, Mehmet Caglar Cakici2, Harun Ozdemir3, Okan Bas2, Nihat Karakoyunlu2, Levent Sagnak2, Aykut Bugra Senturk4, Hamit Ersoy4 Purpose: In this retrospective study, we aimed to compare the outcomes in patients who have been treated with percutaneous nephrolithotomy (PNL) and retrograde intrarenal surgery (RIRS) on renal stones ≥ 2 cm size. Materials and Methods: We evaluated patients who underwent PNL or RIRS for renal stones ≥ 2 cm size between November 2011 and November 2014. Stone size, operation, fluoroscopy and hospitalization time, success rates, stone-free rates and complication rates were compared in both groups. Patients were followed for three months. Results: 254 patients were in the PNL Group. 185 patients were in the RIRS Group. The mean age was 46.88 and 48.04 years in PNL and RIRS groups, respectively. The patient and stone characteristics (age, gender, Body Mass Index, kidney anomaly, SWL history and stone radioopacity) were similar between two groups. The mean stone size preoperatively was significantly larger in patients who were treated with PNL (26.33mm.vs 24.04 mm.; P = .006). In the RIRS group, the mean stone number was significantly higher than PNL group (P < .001). The mean operative, fluoroscopy and hospitalization time were significantly higher in PNL group (P < .001). The stone-free rate was 93.3% for the PNL group and 73.5% for the RIRS group after first procedure (P < .001). No major complication (Clavien III–V) occurred in the RIRS group. Conclusion: Although the primary treatment method for renal stones ≥ 2cm size is PNL, serious complications can be seen. Therefore, RIRS can be an alternative treatment option in the management of renal stones ≥ 2 cm size. Keywords: percutaneous nephrolithotomy; retrograde intrarenal surgery; urolithiasis INTRODUCTION Currently, shock wave lithotripsy(SWL), retrograde intrarenal surgery(RIRS) and percutaneous neph- rolithotomy(PNL) are the three main modalities for renal stone treatment. The European Association of Urology and American Urological Association guide- lines for the treatment of renal stones >20mm recom- mend percutaneous nephrolithotomy as the first-line therapy, independent of stone location within the kid- ney(1,2). PNL has an excellent success rate in clearing stone burden at reported rate up to 96,1%(3). Despite its effectiveness, serious complications, such as blood loss, sepsis, adjacent organ injury and life-threatening medical complications are rare but still a source of con- cern(4). Therefore, there have been efforts to modify the procedure to decrease potential complications (such as mini-PNL, ultra mini-PNL)(5-7). The aim of all these efforts is to apply more effective treatment choices and less invasive methods to patients, to reduce complications and to return to ensure a nor- mal life as soon as possible. RIRS has recently been a very impressive treatment option for the majority of re- nal stones, as a result of the technological advances and developments in flexible ureteroscope, it can minimize the risks associated with PNL as an outpatient proce- dure(1). RIRS is approved as effective and minimally in- vasive procedure with achieving higher stone-free rates than SWL and lower morbidity than PNL(8). However, RIRS may be a first-line option for larger stones (even ≥ 2 cm size) in patients where PNL is not an option or contraindicated(1). Moreover, several groups have demonstrated excellent success rates with RIRS for large renal stones and it has already replaced PNL as a first choice treatment for renal stones requiring active treatment at some centers(9-11). In this retrospective study, we aimed to compare the outcomes of patients who have been treated with standard PNL and RIRS on renal calculi ≥2 cm size. Recently, several authors have reported similar studies in a limited number of patients(3,12). To the best of our knowledge, this study is the largest cohort that com- pares these methods directly in the management of large renal calculi (> 2cm size). We aimed to compare the effectiveness and safety of PNL and RIRS in the 1Department of Urology,Sarikamis State Hospital, Kars, Turkey. 2Department of Urology, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey. 3Department of Urology, Haseki Training and Research Hospital, Istanbul,Turkey. 4Department of Urology, Hitit University, Faculty of Medicine, Çorum, Turkey. *Correspondence: Department of Urology,Sarikamis State Hospital, Kars, Turkey. Phone: +905356608838. E-mail: sercansari92@hotmail.com. Received August 2016 & Accepted December 2016 Endourology and Stone Diseases 2949 treatment of renal stones sized ≥ 2 cm. MATERIALS AND METHODS In this study, we retrospectively reviewed patients data who underwent standard PNL or RIRS for renal calculi sized ≥2 cm by the same surgical team at a single insti- tution between November 2011 and November 2014. Treatment method was chosen according to the urol- ogist and patients preference after assessing both po- tential risks and benefits (complication rates, stone-free rates, the passage of residual fragments, possible opera- tive times and re-treatment rates, postoperative double-J stent placement, etc.) of each surgical option. Patients with an ureteropelvic junction obstruction, anomalous kidneys (except horseshoe kidney), a history of open or percutaneous interventions to the ipsilateral kidney, <18 years of age, or those having a solitary kidney were excluded. A total of 439 patients met these criteria and were divided into two groups according to the proce- dure performed; PNL Group n = 254, and RIRS Group n=185. The demographics of the patients and operative outcomes were compared. Preoperative patient assessment included medical histo- ry, physical examination, complete blood count, serum biochemistry, urinalysis and urine cultures, coagulation profiles, and by the use of different imaging methods (kidney ureter bladder (KUB) graphy, ultrasonography (USG), intravenous urography and/or computed to- mography). A preoperative negative urine culture was required before surgery, so any positive urine cultures were treated according to the antibiogram results. Stone size was defined as the maximum diameter of the stone on computed tomography. In cases of multiple stones, stone size was defined as the sum of the longest axis of each stone. Informed consent was taken from all pa- tients preoperatively. PNL technique All PNL procedures were performed under general anesthesia.Patients were placed in the lithotomy po- sition.Cystourethroscopy was made for open ended uretheral catheter insertion. After uretheral catheter in- sertion , percutaneous access was achieved by C-arm fluoroscopic guidance using an 18-gauge needle with the patient in a prone position. A 0.035-inch J-tipped guidewire was passed through the needle and into the collecting system under fluoroscopic guidance, and the nephrostomy tract was dilated up to 30 f with polyu- rethane serial Amplatz dilators(Microinvazive,Natick,- MA) or metal Alken dilators. A 30F Amplatz sheath was then placed over the dilators. All steps of tract dila- tion and sheath placement were done under fluoroscop- ic imaging. Stone fragmentation was accomplished with pneumatic lithotripter (Lithoclast; EMS, Nyon, Switzerland) and the stones fragments removed with forceps through a rigid nephroscope (26F, Karl Storz®). A nephrostomy tube was placed in all the patients at the end of the procedure(13). Time between entering the cystoscope and nephrostomy tube placement was defined as operation time. RIRS technique All RIRS procedures were applied under general anes- thesia with the patient placed in the lithotomy position and semi-rigid ureteroscopy was routinely performed before flexible ureteroscopy to facilitate the ureter dil- atation for insertion of access sheath.. A 0.035/0.038- inch hydrophilic safety guidewire was inserted into the renal pelvis under fluoroscopic guidance. Thereafter, a ureteral access sheath (9.5/11.5 F or 11/13 F) (Elit Flex, Ankara, Turkey) was placed over the hydrophilic guidewire in all patients. If the access sheath could not be placed easily, the stent was left approximately 1-2 weeks before repeating the procedure . The flexible ureterorenoscope (Karl Storz, Flex X2, GmbH, Tuttlin- gen, Germany) was inserted through the ureteral access. Stone fragmentation was achieved with a 200 μm hol- mium laser fibers (Dornier Med-Tech GmbH, Medi- las H20, Wessling, Germany) until they were deemed small enough to be passed spontaneously. The small fragments were finally evacuated using a manual pump or tipless nitinol baskets (Zero Tip™; Boston Scientific Microvasive). In the majority of patients, a JJ stent was put into place at the end of the procedure and removed approximately 14-21 days postoperatively as an outpa- tient procedure(11). The repeated session was achieved at intervals of 1–3 weeks in patients with incomplete fragmentation or residual stones which were checked on postoperative day 1 with KUB graphy and USG (if necessary). Time between starting endoscopy and JJ stent placement was defined as operation time. Stone size, operation and fluoroscopy time, hospitali- zation time, postoperative JJ stent placement, success rates, stone-free rates and complication rates (using the modified Clavien grading system) were compared in both groups. Data was reported as the number and per- cent or median (range) as appropriate. Stone clearance was assessed in the operation with fluoroscopic control and the day after surgery by KUB graphy or USG . All patients were evaluated with KUB graphy and USG after one month postoperatively in an outpatient clinic setting. Asymptomatic stones smaller than 3 mm were considered as clinically insignificant urolithiasis. Patients who were stone-free or with clin- ically insignificant urolithiasis one month after the last operation were considered to have been treated success- fully. Patients were followed for three months. Statistical Analysis Analyse of data was made with Statistical Package for the Social Sciences for Windows packet programme (SPSS, Chicago). Distribution of numerical measure- ment values was tested with One-Sample Kolmogo- rov-Smirnov Test. If p value was < 0.05, distribution was not normal. Differences in terms of gender, renal abnormality, stone side and localization, bleeding, DJ usage, residual stone presence, opacity, success after the first session, complication, hydronephrosis, preop- erative surgery and SWL history between two groups were searched with Pearson chi-Square test. Differenc- es in terms of age, weight, preoperative hemoglobin val- ue between two groups were evaluated with Student’s t test. Differences in terms of height, American Society of Anesthesiologists (ASA) scores, stone number, stone size, operation time, hospital stay, preoperative urea and creatinine and body mass index (BMI) between two groups were evaluated with Mann-Whitney U test. In PNL and RIRS groups, whether changes in preopera- tive and postoperative hemoglobin, urea and creatinine were significant, were measured with Wilcoxon Signed Ranks Test. P < 0.05 was considered statistically sig- nificant. RIRS and PNL for stones ≥2 CM-Sari et al. Vol 14 No 01 January-February 2017 2950 RESULTS In our study 254 patients were in the PNL Group. 185 patients were in the RIRS Group. The mean age was 46.88 and 48.04 years in PNL and RIRS groups respec- tively. The patient and stone characteristics(age, gen- der, Body Mass Index(BMI), kidney anomaly, SWL history and stone radioopacity) were similar between two groups. The mean stone size preoperatively was significantly larger in patients who were treated with PNL, with the average size for RIRS being 24.04 mm. and that for PNL being 26.33 mm. (P = 0.006). In the RIRS group, the mean stone number was significantly higher than PNL group (P < 0.001). The demographic data and stone characteristics are summarized in Table 1. Eleven patients in the RIRS group and eight patients in the PNL group had horseshoe kidney. In the RIRS group, 57 patients and 70 patients in PNL group had previously undergone unsuccessful SWL applications. The mean operative time, fluoroscopy screening time and hospitalization time were significantly higher in PNL group (P < 0.001, for all of them). In one patient access sheath was not placed and JJ stent was placed 2 weeks before the second procedure. However, postop- erative JJ stent placement was also significantly higher in the RIRS group (P < 0.001). The stone-free rate was 93.3% for the PNL group and 73.5% for the RIRS group after a single procedure (P < 0.001). In the RIRS group, 23 patients had asymptomat- ic residual fragments < 10 mm in the lower pole of the kidney and were followed without any intervention; 22 required additional procedure (SWL in 1, second RIRS in 16, PNL in 5) and all of them were completely stone free, resulting in an overall success rate of 85.4%. Four patients were also lost the follow-up in RIRS group. In the PNL group, the success rate increased to 94.8% after a RIRS intervention (in 4 patients). Thirteen pa- tients were followed without any intervention due to the asymptomatic residual fragments. When we look at the complication (major and minor) rates, the difference was not statistically significant (P = .058). Five patients in the PNL group received blood transfusions, whereas none of the patients in RIRS group were transfused. No major complication (Clavien III–V) occurred in the RIRS group. However, there were four major complications (1.5%) in the PNL group. Three patients suffered from prolonged urine leakage (Clavien III) which was treated with a JJ stent. One patient died (Clavien V) due to cardiac arrest. Op- erative and postoperative data are summarized in Table 2. DISCUSSION PNL is recommended as a first line treatment option in the management of renal stones sized ≥ 2 cm(1,2). How- ever, life-threatening complications can be seen. An- other treatment method is RIRS. Arising in 1990’s, use of RIRS has increased by developing technology and extending experience(14). Development in new flexible renoscopes and laser technology led to increase in area of use of this method(15-17). In the literature, there are studies about the usage of RIRS for the treatment of renal stones sized ≥ 2 cm. Breda et al. reported a success rate of 93.3% for 15 pa- RIRS and PNL for stones ≥2 CM-Sari et al. PNL Group (n=254) RIRS Group (n=185) p value Age (mean ± SD) (years) 46.88 ± 14.35 48.04 ± 14.09 ns. Gender; Male/Female (n) 155/99 111/74 ns. Mean BMI (kg/m2) 27 ± 3.78 25.71 ± 3.02 ns. Anomalous kidney, n (%) 8 (3.1) 11 (5.9) ns. History of SWL, n (%) 70 (27.6) 57 (30.8) ns. Radioopacity of stone, n (%) Non-opaque 26 (10.2) 20 (10.2) ns. Opaque 228 (89.8) 165 (89.8) Stone laterality; Right/left (n) 120/134 89/94 ns. Stone number (mean ± SD) 1.5 ± 0.1 2.0 ± 0.1 < 0.001 Stone size (mean ± SD) (mm) 26.33 ± 0.44 24.04 ± 0.39 0.006 Stone location, n (%) Renal pelvis 102 (40.2) 62 (33.5) Lower calyx 66 (24.4) 52 (28.2) Middle calyx 12 (4.7) 25 (13.5) < 0.001 Upper calyx 8 (3.1) 13 (7) Multicaliceal 70 (27.6) 33 (17.8) Table 1: Demographic data and stone characteristics Abbreviations: SD, standard deviation; BMI,Body Mass Index; SWL, Shock Wave Lithotripsy; RIRS, Retrograde Intrarenal Surgery; PNL, Percutaneous Nephrolithotomy; ns, non significant Endourology and Stone Diseases 2951 tients with renal stones of 20-25 mm(10). Mariani et al. reported a success rate of 92% in 15 patients with renal stones of 2-4 cm size(18). Grasso et al. reported a success rate of 91% for 51 patients with renal stones sized ≥ 2 cm(19). Palmero et al. applied RIRS to 106 patients with renal stones sized ≥ 2 cm(20). Hyams et al. stated a success rate of 85% for 120 patients with renal stones of 2-3 cm size for the study in which RIRS method was applied(21). There are few studies comparing RIRS and PNL meth- ods for treatment of renal stones 2-4 cm in size. In their research in which 68 patients were included and RIRS and PNL methods were compared, Akman et al. found the success rates of 91.2% and 73.5% for PNL and RIRS groups, respectively(22). In the follow-up conduct- ed three months later, success rates of 97% and 94.1% were found for PNL and RIRS groups, respectively. Bryniarski et al. compared RIRS and PNL methods in 64 patients with pelvis stones of 2-4 cm size in a pro- spective study(23). Success rates of 81.25% and 50% were detected for PNL and RIRS groups, respectively and the success rates of 93.75% and 75% were report- ed after a follow-up study of 3 weeks. De et al. com- pared the RIRS and PNL methods in their review(24). The stone size was between 2- 4 cm in only two of ten studies taken into consideration. In our study, RIRS and PNL methods were compared in 439 patients with renal stones sized ≥ 2 cm. The follow- ing success rates were found: 93.3% and 73.5 for PNL and RIRS groups, respectively and 94.9% and 85.4% for the same groups in terms of total success rate. The results were similar to those found in studies in the lit- erature. In our study, the operation duration was found to be 79.2 Table 2: Per-operative and Postoperative data PNL Group (n=254) RIRS Group (n=185) P value Operation time (min) 79.25 ± 35 54.29 ± 14.09 < 0.001 Fluoroscopy screening time (min) 6.5 ± 4.97 1.04 ± 1.32 < 0.001 Preferred Access, n (%) Lower calyx 244 (97) - Middle calyx 10 (3) Hospitalization time (day) (mean ± SD) 3.94 ± 1.22 1.02 ± 0.23 < 0.001 Double-J placement, n (%) 76 (30) 155 (83.8) < 0.001 Stone-free status, n (%) Stone free 229 (89.8) 151 (72.6)a /167 (80.3)b /168 (80.7)c CIRF d 9 (3.5) 5(2.4)a /0 (0)b /0 (0)c Rest 17 (6.7) 52 (25)a/ 41 (19.7)b /40 (19.3)c Success rates e, n (%) 237 (93.3) 136 (73.5) < 0.001 Complication rates, n (%) 21 (8.3) 7 (3.8) ns. Minor (Clavien I-II) Complications Fever 12 (4.72) 7 (3.8) Blood transfusion 5 (1.96) - Urinary tract infection 7 (2.75) 7 (3.8) Major (Clavien III-V) Complications JJ placement for urine leakage 3 (1.18) - Death 1 (0.39) - Auxiliary procedure, n (%) SWL - 1 (0.005) RIRS 4 (1.57) 16 (8.67) PNL - 5 (2.7) Observation 13 (5.11) 23 (12.7) Abbreviations: SD, standard deviation; BMI, Body Mass Index; SWL, Shock Wave Lithotripsy; RIRS, Retrograde Intrarenal Surgery; PNL, Percutaneous Nephrolithotomy; ns, non significant a: 1st RIRS sessions, b: 2nd RIRS sessions, c: 3rd RIRS sessions d: Clinically insignificant residual fragments e: Success is defined as stone free + CIRF RIRS and PNL for stones ≥2 CM-Sari et al. Vol 14 No 01 January-February 2017 2952 ± 34.9 and 54.29 ± 14.09 minutes for PNL and RIRS groups, respectively. The efforts for stone clearence are one reason for this result. Akman et al. indicated the op- eration durations of 38.7 ± 11.6 and 58.2 ± 13.4 minutes for PNL and RIRS groups, respectively(22). In another study, Bryniarski et al. reported 100.1 and 85 minutes for the PNL and RIRS groups, respectively(23). In our study, the scopy time was determined to be 6.5 ± 4.97 and 1.04 ± 1.32 minutes for PNL and RIRS groups, respectively. The results were similar to those found in studies in the literature. The difference was explained on the basis of taking scopy for entry to kidney via per- cutaneous access. In terms of hospitalisation period, we determined the periods of 3.94 ± 1.22 and 1.02 ± 0.23 days for PNL and RIRS groups, respectively. The period passing for tak- ing percutaneous nephrostomy led to increase in hos- pitalisation time in the PNL group. Applying tubeless PNL may shorten this period. The decision for tubeless PNL is made on the basis of existence or nonexistence of intraoperative bleeding, residual stones or perfora- tion. Tubeless PNL was not applied to any patient in our research. In terms of bleeding status, it was significantly higher in PNL group compared to RIRS group. It was associated with longer operation duration. In their research, Ak- man et al. concluded that the need for blood transfusion increases by 2.82 times in PNL operations longer than 58 minutes(25). When complication rates are taken into consideration, although more complication was seen in PNL group, the difference was not statistically significant. No major complication was seen in RIRS group. In PNL group major complications were seen. In PNL group one pa- tient died due to cardiac arrest. The number of minor complications were higher in PNL group but the differ- ence was not statistically siginificant. When the litera- ture is assessed, life-threatening complications may be seen in PNL operation. These are transfusion-requiring bleeding, septicaemia, colon injury, hemothorax, fever and urinary system infection. In our study, one of our patients died. Transfusion-requiring bleeding was de- tected at the rates of 0.8% to 45% in PNL operation in literatüre(26-28). Significant complications are not ob- served in RIRS operation due to developing technolo- gy. Mini and ultra mini PNL can be applied to prevent the complications due to the sheath size. In our study JJ stent usage was higher in the RIRS group. The major reason is access sheath usage .Anoth- er reason is residuel stones. The stone free rates were lower in the RIRS group . If we look at limitations of our study, its being retro- spective is a disadvantage. Due to retrospective nature, stone size was different between the groups. Another limitation is short patient follow up. Therefore an im- portant complication related to access sheath usage in RIRS was not seen in our study. When previous studies are taken into consideration, it is the largest study in the literature in terms of number of patients. For treatment of renal stones sized < 2 cm RIRS can be used as first line treatment(29). RIRS can be used for patients not requesting invasive treatment for stones of sized ≥2cm. Total cost level is a disadvantage to RIRS. Its shorter duration of hospital stay and operation as well as lower complication levels can compensate this dis- advantage. Another disadvantage is that it may require multiple sessions. PNL can be taken into consideration for patients requesting treatment in single session. As a conclusion, ≥ 2sized stone treatment is one of the controversial issues in urology. PNL is more effective than RIRS in treatment of these stones. And primary treatment method. Although the primary treatment method is PNL, significant complications can be seen. RIRS can be taken into consideration in cases not re- quiring invasive treatment. Comprehensive and pro- spective studies are needed. CONFLICT OF INTEREST No competing financial interests existed. REFERENCES 1. 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