ENDOUROLOGY AND STONE DISEASE Flexible Ureterorenoscopy versus Semirigid Ureteroscopy for the Treatment of Proximal Ureteral Stones: A Retrospective Comparative Analysis of 124 Patients Mert Ali Karadag,1* Aslan Demir,1 Murat Bagcioglu,1 Kursat Cecen,1 Ramazan Kocaaslan,1 Fatih Altunrende2 Purpose: To investigate and compare the stone clearence and complication rates of flexible ureteroscopy (URS) with semirigid URS in patients having proximal ureteral stones. Materials and Methods: The data of 124 patients with proximal ureteral stones who underwent semirigid or flexible ureterorenoscopic lithotripsy between March 2008 and December 2012 were retrospectively investigated. The patients were divided into 2 groups according to the operation types. Group 1 included 63 patients who were treated with semirigid URS and group 2 was consisted from 61 patients who underwent flexible URS. Each group was compared in terms of stone diameter, successful access to the stone, operation time, reoperation rates, stone free status at postop- erative 1st and 3rd month and complications. Results: Successful access was achieved in 48/63 (76%) of the cases in group 1 and 57/61 (93%) of the patients in group 2 (P < .05). Initial stone free status was 63.4% (40/63) and 86.8% (53/61) in groups 1 and 2, respectively (P < .05). Third month radiologic investigations revelaed a stone free rate of 77.7% (49/57) in group 1 and 93.4% (57/61) in group 2 (P < .05). Reoperation was required in 20.6% (13/63) of cases in group 1 and this value was only 6% (4/61) in group 2 (P < .05). There was not any statistically significant difference between 2 groups in terms of complication rates (P > .05). Conclusion: Flexible URS is a favorable option for patients having proximal ureteral stones with higher stone free rate; on the other hand semirigid URS seems a less successful alternative for treatment of proximal ureteral stones. Keywords: ureteral calculi; surgery; ureteroscopes; ureteroscopy; lithotripsy; retrospective studies; treatment out- come; complications. INTRODUCTION Proximal ureteral stones can be managed by various techniques including extracorporeal shock wave lithotripsy (SWL), ureterorenoscopy (URS) with semirigid or flexible instruments, laparoscopic approach- es, antegrade ureterolithotripsy and open surgery. The de- cisions about the choice of therapy depends on the stone factors like localization, size, density and radiolucency, anatomical factors, obstruction, technical capacity of the department, patient’s preference and surgeon’s skills.(1,2) SWL and URS have been accepted as the initial treatment alternatives for proximal ureteral stones having low prob- ability of spontaneous passage. SWL has been considered as the first line treatment alternative for patients having proximal ureteral stones < 10 mm due to noninvasiveness and lower complication rates.(3) The major disadvantages of SWL are long duration of treatment and requirement for auxillary procedures. With the miniaturization and advancements in the designs of ureterorenoscopes, stone disintegration systems and endourologic techniques, most of the ureteral stones can be managed by URS now- 1 Department of Urology, Kafkas University, Faculty of Medicine, Kars, Turkey. 2 Department of Urology, Istanbul Bilim University, Faculty of Medicine, Istanbul, Turkey. *Correspondence: Kafkas Üniversitesi Tıp Fakültesi Hastanesi, Üroloji A.B.D, Kars, Türkiye. Tel: +90 532 5584324. E-mail: karadagmert@yahoo.com. Received March 2014 & Accepted October 2014. adays. Usage of holmium:YAG laser during URS makes the stone clearence better in a single session even for the proximal ureteral stones > 10 mm.(4) Many studies to date have investigated the superiority and outcomes (in terms of complication rates and stone free status) of SWL, retrograde intrarenal surgery and laparos- copy over each other for the treatment of proximal ureter- al stones.(5,6) To the best of our knowledge, there has been no published article investigating and comparing the out- comes of flexible URS (F-URS) against semirigid URS for treatment of proximal ureteral stones. In the present study, we investigated and compared the stone clearence and complication rates of F-URS against semirigid URS in patients having proximal ureteral stones. MATERIALS AND METHODS The medical files of 228 patients with solitary proxi- mal ureteral stones who underwent semirigid URS or F-URS in Kars State Hospital, Kafkas University, Facul- ty of Medicine and Acibadem Kayseri Hospital between Vol 11. No 05 Sept-Oct 2014 1867 March 2008 and December 2012 were reviewed and database of the study was formed. Semirigid URS was performed in 108 patients and 120 underwent F-URS. According to the data searched, a total of 124 patients with solitary proximal stones who underwent semirigid URS or F-URS with holmium:YAG laser were enrolled in this study. Inclusion criteria of the study was patients who were operated for solitary proximal ureteral stones with semirigid or F-URS and who had postoperative 1st and 3rd month radiological investigations for assessment of stone free status in the medical records. Patients with ureteral calculi who were previously operated or treated with SWL, cases with ureteropelvic junction obstruction, solitary kidneys or multiple stones and the patients under 18 years old were excluded from the study. Semirigid URS group included the patients who were operated in Kars Sate Hospital and Kafkas University, Faculty of Medicine. F-URS group consisted of the pa- tients who were operated in Acibadem Kayseri Hospital. Review of the complete medical records of the patients for our study was approved by local ethics committee of Kafkas University, Faculty of Medicine and performed in accordance with the Helsinki Declaration of the World Medical Association. Proximal ureteral stones were defined as the stones lo- cated between the superior margin of the sacroiliac joint and the ureteropelvic junction. All of the patients were preoperatively evaluated with a detailed history, physi- cal examination, laboratory tests including renal function tests, urine analysis and urine culture. The imaging in- vestigations were plain X-ray of the kidneys, ureter and bladder (KUB), urinary ultrasonography and non contrast computed tomography (CT) scan of the abdomen in pa- tients with radioluscent stones. Stone status was assessed intraoperatively and with post- operative 1st and 3rd month plain X-ray of the KUB, urinary ultrasonography and non contrast CT scan of the abdomen in patients having radioluscent stones. Success was accepted as patients with no stones or clinically in- significant residual fragments (< 4 mm) observed at ini- tial postoperative evaluation and 1st/3rd month radiolog- ic investigations. Stone size was measured by using the longest axis of the stone viewed on plain film or sagittal section of CT scan. Surgical Procedures All of the patients were operated under general anesthe- sia at the lithotomy position. Cephazolin sodium 1 gr intravenous was administered for preoperative antibiotic prophylaxis. Semirigid URS was performed by using a 6.0/7.5 French (F) ureteroscope (Richard Wolf, Knittlin- gen, Germany). First, we introduced a safety guide wire (Microvasive, Boston Scientific Corp, Natick, MA, USA) to the ureter with stone, then the semirigid ureteroreno- scope was inserted into the ureter over guide wire under direct vision. After reaching the stone, disintegration was completed by using 20 W holmium:YAG laser (Lumenis, Santa Clara, CA, USA). A 200-µm laser fiber with an energy output of 0.8-1.5 joule at 8-12 hertz was used; but the joule and hertz of energy could be changed during the operation according to the stone hardness and efficacy of lithotripsy. The main goal was to disintegrate the stones until the fragments were smaller than 4 mm under direct vision or completely extraction of the stone fragments with basket (Zero Tip™, Boston Scientific Corp, Natick, MA, USA). F-URS was performed using a 7.5 F flexible ureteroreno- scope (Karl Storz, Tuttlingen, Germany). After the inser- tion of a 9/11 F access sheath (Cook Urological, Spencer, Indiana, USA) over a sensor guide wire (Microvasive, Boston Scientific Corp, Natick, MA, USA) under C arm fluoroscopy, we inserted the F-URS into the ureter and completed the stone disintegration and extraction like in the semirigid URS procedure. For both treatment groups, we inserted 26 cm 4.8 F dou- ble J ureteral catheters over the guide wires at the end of the procedures. It is a routine application in our de- partment and urology department of Acibadem Kayseri Hospital after the treatment of proximal ureteral stones. Statistical Analysis Results are presented as the mean ± Standard deviation (SD). The data were analyzed by Statistical Package for the Social Science (SPSS Inc, Chicago, Illinois, USA) version 16.0. Categorical variables were analyzed using chi-square test and statistical analyses of the means of continuous variables were performed with the Student’s t-test. A P value of < .05 was considered statistically sig- nificant. Each group treated with semirigid URS and F-URS for proximal ureteral stones were compared in terms of stone diameter, successful access to the stone, operation time, reoperation rates, stone free status at 1st and 3rd month and complications like fever, bleeding and perforation. Reoperation was defined as requirement of same modal- ity in patients with residual stones or stones > 4 mm in radiologic evaluation. Bleeding was accepted as hemor- rhage that disrupted the endoscopic vision of the surgeon and ureteral injury was defined as mucosal trauma that was observed during URS applications. Bleeding and ureteral injury were decided by the urologists who per- formed the operations. RESULTS Patients’ characteristics and demographics of 2 groups were summarized in Table. There was not any statisti- cally significant difference between two groups in terms of age, gender, stone size and opacity (P > .05). As ex- pected, the mean operation time of group 1 was signifi- cantly shorter than group 2. With regards to success rate of reaching to the stone, we could make a successful ac- cess and reach to the stone in 48/63 (76%) of the cases in group 1 and 57/61 (93%) of the patients in group 2. This value was statistically significant (P = .008) and showed the superiority of F-URS in reaching to the proximal ure- teral stones. In patients of group 1 with unsuccessful ac- cess to the stones (n = 9) (5 tortuosity, 2 narrow caliber of the ureter and 2 serious stenosis) and stone migration into the kidneys (n = 6), we inserted 26 cm 4.8 F double J catheters and operations were terminated. They were referred to another center for SWL or F-URS applica- tions and excluded from the study in terms of stone free achievement. In patients of group 2 with unsuccessful ac- cess to the stone (n = 4), same aforementioned modality was preferred. The reason of unsuccessful access in these patients was narrow caliber of the ureters (summarized in the flow chart). Flexible Ureterorenoscopy vs. Semirigid Ureteroscopy-Karadag et al Endourology and Stone Disease 1868 Initial stone free status which was achieved after disinte- gration of the stones < 4 mm or complete extraction of the fragments decided by the surgeon at the end of the pro- cedure was 63.4% (40/63) and 86.8% (53/61) in groups 1 and 2, respectively. This result was statistically signif- icant (P = .003). This rate increased to 71.4% (45/63) in group 1 and 90.1% (55/61) in group 2 (P = .008) at 1st month radiologic controls. Third month radiologic inves- tigations revelaed a stone free rate of 77.7% (49/63) in group 1 and 93.4% (57/61) in group 2 (P = .013). All these results showed us the superiority of F-URS in terms of achieving a stone free status. Reoperation rates of 2 groups were compared in our study. We required reoperation in cases who had rest stones or stones > 4 mm in radiologic evaluations. Reoperation was required in 13/63 (20.6%) of cases in group 1 this value was only 6% (4/61) in group 2. Reoperation rate of group 2 was statistically lower than group 1 (P = .023). Complications were classified according to the modified Clavien Grading system.(7) No major intraoperative com- plications (grade 4 or 5) like avulsion or septicaemia were observed. Ureteral perforation (grade 3B) below the uret- eropelvic junction occured in 1 patient from F-URS group and managed conservatively with insertion of a 26 cm 4.8 F double J ureteral catheter. The complication rates of 2 groups in terms of fever, bleeding and ureteral injury were compared. Postoperative fever (grade 1) was ob- served in 7 (11.1%) patients from group 1 and 8 (13.1%) patients from group 2 (P = .732). Bleeding (grade 1) was noted in 13 (20.6%) and 5 (9.8%) patients from group 1 and 2, respectively (P = .095). Ureteral injury (grade 1) occured in 4 (7.9%) and 2 (3.2%) cases from groups 1 and 2, respectively (P = .261). There was not any statistically significant difference between 2 groups in terms of com- plication rates. DISCUSSION The success rate of SWL in proximal ureteral stones larg- er than 10 mm varies between 57-96% in the literature. (8,9) Patient’s and urologist’s preference of SWL therapy mainly depend on the advantage of less invasiveness with lower complication rates.(3) In our department, we also have a SWL machine and therapy choice of proximal ure- teral stones are decided after explaination of the options and discussion with the patients. All of the patients who were included in our study preferred ureterorenoscopic procedures as therapeutic modality. Recent developments in the market about miniaturization of semirigid and F-URS and holmium:YAG laser in URS applications attracted the attentions’ of the urologists and markedly improved the success rates of treating proximal ureteral and renal stones. Atis and colleagues investigat- ed the efficacy of semirigid URS against F-URS in treat- ment of renal pelvis stones.(10) The study included 47 pa- tients with isolated renal pelvis stones. Successful access with semirigid URS was achieved in 25 of 47 patients and the stones were fragmented using holmium:YAG laser. F-URS was performed in remaining 22 patients. Variables Semirigid URS Flexible URS P Value No. of patients 63 61 Mean age (year)* 38.2 ± 9.85 36.2 ± 7.38 .214 Stone diameter (mm)* 11.6 ± 2.20 11.01 ± 2.24 .107 Sex** .697 Female 29/63 25/61 ----- Male 34/63 36/61 ----- Laterality** .474 Right 34/63 29/61 Left 29/63 32/61 Radioluscent** 7/63 6/61 .817 Operation time (min)* 64.71 ± 16.11 84.06 ± 16.7 .001 Table. Demographic and clinical characteristics of study groups. Abbreviation: URS, ureteroscopy. *Student t-test (P > .05) **Chi-square test (P > .05) Flexible Ureterorenoscopy vs. Semirigid Ureteroscopy-Karadag et al Flow Chart Vol 11. No 05 Sept-Oct 2014 1869 The authors revealed no significant differences among 2 groups in terms of stone free rates, complication rates and hospitalization. An approximately success rate of 50% improved to 90% in the treatment of proximal ureteral stones after development of small caliber URS and hol- mium:YAG laser.(11-14) The major disadvantage of holmi- um:YAG laser seems to be the cost; but we also prefer to use holmium:YAG laser for treating patients with prox- imal ureteral stones as energy source in our department. In a recent study from India, 90 patients having upper ureteral stones < 2 cm were treated with shockwave lith- otripsy and semirigid URS and outcomes were compared. (15) Ureteroscopy and stone disintegration were performed by using an 6/7.5 F semirigid URS with holmium:YAG laser. The average stone size of URS group was 12.5 mm and the overall 3rd month stone free rate was 86.6%. In our study, the mean stone size of patients treated with semirigid URS was 11.6 mm and 3rd month success rate of this group was 77.7%. The average stone diameter of 2 studies were similar; but the other group’s success rate was higher. This may attribute to the experience of the other group in treating proximal ureteral stones and technical armamentarium of the clinics. In our opinion, if we had F-URS, stone-cone® or N-Trap® basket in the clinics of Kars State Hospital and Kafkas University Fac- ulty of Medicine, the success rate of semirigid URS group would be higher. After introduction of flexible systems into urology, the stone free rate was significantly increased for the treat- ment of the patients having proximal ureteral stones.(16,17) In a recent study, Liu and colleagues investigated the outcomes of 187 patients with proximal ureteral stones who were treated with ureteroscopic lithotripsy using hol- mium:YAG laser.(18) They reported that with the aid of F-URS and N-Trap® basket, the success rate improved to 88.9% and achievement of a stone free state after sem- irigid URS procedures would be possible. Endourolog- ical Society Ureteroscopy Global Study Group recently published their article dealing with differences in uret- eroscopic stone treatment and outcomes in patients with distal, mid, proximal, or multiple ureteral locations.(19) Of 9681 patients, 2656 received ureteroscopy treatment for stones locataed in the proximal ureter. Semirigid URS with laser or pneumatic lithotripsy were used in the ma- jority of cases. They revealed a stone free rate of 84.5% for proximal ureteral stones. Similar to our study, failure and retreatment rates were significantly higher for semi- rigid URS, when compared to F-URS. A new study from Korea investigated the effectiveness of flexible uretero- scopic stone removal for treating ureteral and ipsilateral renal stones.(20) The study included 74 ureteral stones of which 46 located in the upper ureter, 10 in the middle ureter and 18 in the lower ureter. They achieved a stone free rate of 100% for ureteral stones; but the mean size of the ureteral stones was not reported in the study. Instead of average stone size term, they used cumulative stone burden which also included the sizes of ipsilateral renal stones. In our study, the initial success rate of F-URS group was 86.8% and this rate increased to 93.4% at the end of 3rd month. The overall success rate of F-URS group was statistically higher than semirigid URS group. In our opinion, the treatment of patients of semirigid URS group having unsuccessful access to the stone or stone migration into the kidneys could be completed by using F-URS. Unfortunately, the urology departments of Kars State Hospital and Kafkas University, Faculty of Medi- cine had not had F-URS until 2012. Nowadays, we have capability of using F-URS in patients with proximal ure- teral or renal stones. Most of the urologists prefer to dilate the ureter “optical- ly’’ by using a semirigid URS prior to F-URS. Besides this, we did not perform optical dilatation before flexible procedures in our study and they were performed after insertion of 9/11 F access sheaths over the guide wires. Instead of switching to F-URS in the operation, we rather prefer to start the procedure with flexible instrument and disintegrate the stone with the same modality. Stone access rates in our study showed us that F-URS was statistically superior against semirigid URS (93% vs. 76%). This difference may be attributable to the use of access sheath prior to the flexible procedure. The appli- cation of ureteral access sheath carries many advantag- es like outflow of irrigation fluid which facilitates clear vision for the surgeon, avoiding of high renal pressure which could decrease septicemia risk and obtain ex- pulsion of stone fragments, preventing mucosal trauma during the procedure and prolonging the active life of F-URS.(18) Except of 4 cases with narrow caliber of ure- ters, we introduced access sheaths to all patients prior to the flexible procedures and we did not face with any difficulties in application of the access sheaths over guide wires. In our opinion, factors that complicate access to stones like tortuousity of the ureter, angulations and se- rious edema at the stone site could be defeated by using access sheath and F-URS. Retreatment rate of semigid URS varies between 4% and 23% in the literature.(21-23) Our study revealed a reopera- tion rate of 20.6% for semirigid URS group. This result was similar with the rate of Basiri’s and Nikoobakht’s studies.(22,23) Basiri and colleagues found reoperation rate in their study as 22%; on the other hand Salem and col- leagues(21) revealed a reoperation rate of 4%. In our opin- ion, the heterogenity in reoperation rates depends on the mean stone sizes of the studies. The mean stone size of patients who were treated with semirigid URS in Salem’s study was approximately 7 mm; but the average stone size of the patients in Basiri’s study was 1.8 ± 0.2 cm. Lee and colleagues reported a reoperation rate of 42% with F-URS for the patients having large upper third ure- teral stones.(17) In our study, reoperation rate of F-URS group was only 6%. This disparity could be explained again with the difference in average stone diameters of the studies. The mean stone size in Lee’s study was 1.8 ± 0.3 cm, on the other hand our study’s average stone size of patients treated with F-URS was 11.01 mm. It seems that the requirement for auxillary treatments increases with the increase in the ureteral stone diameter. The most important and serious complications of ureter- oscopic lithotripsy are ureteral avulsion and perforation. (18) In the literature, the incidence of ureteral perforation is between 0-1%.(18,20,24) Only in 1 patient from F-URS group, a 2 cm ureteral perforation occured at the edema- tous site below the ureteropelvic junction during tracing a stone which migrated into the kidney. The operation was terminated after insertion of a 26 cm 4.8 F double J ure- teral catheter and left for 6 weeks. After 6 weeks he was reoperated for migrating stone. The comparison between complication rates in terms of fever, bleeding and ure- Flexible Ureterorenoscopy vs. Semirigid Ureteroscopy-Karadag et al Endourology and Stone Disease 1870 teral injury revealed no significant difference between 2 groups. These minor complications were treated conserv- atively and disappeared after 2-3 days. Bleeding and ure- teral injury were more common in patients treated with semirigid URS. We did not terminate any operations due to bleeding or ureteral injury in any cases. We think that it was due to surgeon’s forced forward pushing of semirigid ureteroscope in some cases having angulations, tortuous- ity of the ureter and serious edema at the stone site. In our opinion, these difficulties in reaching the proximal ureteral stones could be defeated by using F-URS with the advantages of deflexion and rotation. There are several limitations of our study. First of all, our study had a retrospective nature and based on a small sample size. In the literature, the “stone free status’’ and clinically insignificant residual fragments (CIRF) terms have not been defined and standardized yet. In our study, we preferred to use CIRF term for stones < 4 mm. There are 3 institutions involving in this study; but procedures were performed by only 3 surgeons. KC performed sem- irigid ureteroscopies, whereas MAK and MS performed flexible procedures. It should be kept in mind that surgi- cal skills may vary from surgeon to surgeon and for this reason making standardization about studies dealing with surgical interventions is very difficult. CONCLUSION Ureteroscopic management of proximal ureteral stones can be achieved by using semirigid or F-URS. F-URS is a favorable option for patients having proximal ureteral stones with higher stone free rate; on the other hand semi- rigid URS seems a less successful alternative for treament of proximal ureteral stones. The semirigid URS should be preferred for management of proximal ureteral stones, if F-URS is involved in department’s armamentarium due to the fact that with the aid of F-URS, success rate of the semirigid procedures will be higher. CONFLICT OF INTEREST None declared. REFERENCES 1. 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