Clinical Application And Evaluation Of Flexible Ureteroscopic Lithotripsy

Background and objectives:With the advancement of new generation of flexible ureteroscope and the emergence of Ho:YAG laser, retrograde intrarenal surgery (RIRS) with flexible ureteroscope plays an increasing important role in the treatment of upper urinary tract stones. Currently, the application of RIRS was not balanced all through China and not standardized in some areas. There have been some questions in the procedure of RIRS application, and also some controversial issues exist. Exactly, there are much more hiding questions that need in-depth research and analysis, such as, the indications, whether the pre-indwelled ureteral stent is needed, the irrigation method, factors affecting postoperative stone-free rate (SFR), the risk factors for postoperative systemic inflammatory response syndrome (SIRS), and so on. This retrospective study was aimed to summarize and analyze the data collected from the First Affiliated Hospital of Guangzhou Medical University in a period of October2012to November2013, where these patients received RIRS for upper urinary tract stones. Treatment results and complications were compared in different groups that diverged from different standards, the indications for RIRS was explored, and the factors that influence the treatment outcome and complications were analyzed, in the aim to improve surgical results and reduce surgical complications. Clinical applicative anatomy knowledge for RIRS was summarized to guide the surgical procedure based on the knowledge of anatomy and clinical work.Materials and Methods: The data of patients received RIRS for upper urinary tract stone in the First Affiliated Hospital of Guangzhou Medical University in a period of October2012to November2013was collected. Of the seven patients who change the surgery method from RIRS to percutaneous nephrolithotomy (PCNL),5patients were male and2patients were female, their stones was located in middle calyx in2patients, lower calyx in5patients, and one patient with stones located in calyceal diverticulum in middle pole. The mean stone burden was1.6±0.7cm (range1.0-2.9) in maximum diameter. At last, a total of260patients were enlisted in this retrospective study, including157male and103female. The mean age was48.4±12.2years (range20-82), with a body mass index (BMI) of23.6±2.3kg/m2(range18.6-28.6). Upper ureteral calculi was noted in27patients (10.4%), kidney stones was noted in133patients (89.6%), mainly distributed in upper calyx in32patients (12.3%), middle calyx in49patients (18.8%), lower calyx in88patients (33.8%), renal pelvis in64patients (24.6%). The mean stone burden was1.7±0.7cm (range0.6-5.0) in maximum diameter. Previous nephrolithotomy in ipsilateral kidney was noted in7patients (2.7%), ESWL in5patients (1.9%), PCNL in30patients (11.5%). For special patients, solitary kidney was noted in31patients (11.9%), spinal deformity was noted in three patients (1.2%), horseshoe kidney was noted in one patient (0.4%), calyceal diverticular calculi was noted in two patients (0.8%), transplanted kidney was noted in one patient (0.4%), hemophilia was noted in one patient (0.4%). Preoperative hemoglobin (Hb) was12.5±0.8g/dL (range10.3-14.0), preoperative positive urine culture due to urinary tract infection (UTI) was noted in47patients (18.1%).All patients were administrated measurement of height and weight to assess body mass index (BMI) after admission. At the same time, fasting blood examination was checked for Hb, coagulation, serum electrolytes, etc. All patients received middle stream urine culture test to assess whether UTI. Complete course of antibiotics based on susceptibility results was required for those with UTI, routine prophylactic antibiotics was administrated to other patients before the surgery. Ultrasonography, intravenous urography (IVU) and CT scan was administrated to get a definite diagnosis, and the knowledge of stone characteristic and location. The stone burden was evaluated with the maximum diameter.Patients signed informed consent for surgery, and then the RIRS procedure was arranged. The surgical instruments for RIRS included rigid ureteroscope, flexible ureteroscope, imaging system (camera, light sources and monitors), guide wire, ureteral access sheath, irrigation pump, syringe, Ho:YAG laser, fiber, stone basket, ureteral stent, etc.All RIRS procedures were performed under general anesthesia in low lithotomy position as one stage procedure technique. Ureteroscopy with semi-rigid8/9.8Fr ureteroscope (Richard Wolf, Germany) was administered. Then, a flexible0.035inch guide wire was inserted into renal collecting system. Ureteral access sheath (Cook Urological, Spencer IN) was inserted into the proximal ureter along the guide wire under fluoroscopy guidance. Olympus URF-P5flexible ureteroscope (Olympus Corporation, Tokyo, Japan) was advanced via ureteral access sheath. Stones were identified and fragmented by Holmium:YAG laser lithotripsy set at0.5-0.8J*10-25Hz. Stone fragments were picked out by2.2Fr Nitinol stone basket. A6Fr double-J ureteral stent was placed at the end of the procedure. Vital signs were closely monitored postoperatively, and the complete blood count, serum electrolytes, KUB was rechecked. Stone composition was analyzed by infrared spectroscopy, and the predominant stone component was recorded. Double-J stent was removed on postoperative two weeks. All patients were assessed by KUB on postoperative1month to confirm the final stone free rate (SFR). Patients with residual stones received regular follow-up or ancillary treatment.Statistical analysis was performed using SPSS for Windows version17.0, P<0.05(two-tailed) was considered statistically significant. Descriptive analysis was performed to evaluate distribution patterns of patient demographic, stone characteristics and operation finding, such as age, BMI, stone burden, lithotripsy time, operation time, irrigation volume, irrigation flow rate, etc. Percentage analysis was performed to evaluate stone clearance rate (SFR), the incidence of SIRS, and other ratios.In order to clarify the impact of solitary kidney, post-PCNL residual stone, lower calyceal stone and irrigation method on the RIRS procedure, subgroup according to whether solitary kidney, post-PCNL residual stone, lower calyceal stone and different irrigation method was diverged, two-tailed t-test was used to determine significance of change in continuous variables whereas categorical data were compared with the Χ2test or Fisher’s exact test for proportions.In the analysis for the risk factors of SIRS and predictors of SFR, groups were diverged based on SIRS and SFR status, and univariate analysis was performed to calculate the potential factors. Independent variables were selected to enter the multivariate logistic regression analysis according to the above Chi-square test and t test results, previous studies, as well as clinical experience. Backward:LR backward stepwise method (likelihood ratio statistic) was selected. The Entry was set at0.10while Removal was set at0.15.Results:Of the seven patients who change the surgery method from RIRS to percutaneous nephrolithotomy (PCNL), flexible ureteroscope cannot touch the stones was noted in4patients, including one case of calyceal diverticular calculi,2patients received further treatment in PCNL because UPJ obstruction. Surgical kidney was noted in one patient, and received percutaneous nephrostomy for drainage.Among the203patients without previous ureteral stent indwelling history,7patients (3.44%) were founded to have a ureteral stenosis and received Double-J stent indwelling. Successful placement of ureteral access sheath was noted in the second ureteroscopy procedure one month later.260patients received RIRS successfully. Intraoperative irrigation was provided with pump in142patients and syringe in118patients, the total irrigation volume for each RIRS procedure was1302.9±784.1ml, and the mean irrigation flow rate was41.4±13.1ml/min. The mean lithotripsy time was34.3±3.0min (range15-76), the operative time was45.4±12.9min (range25-90). Ureteral injury was noted in3patients; no other serious complication was noted, such as ureteral rupture. Postoperative SIRS occurred in21patients, the incidence rate was8.1%, these patients recovered successfully after supportive treatment. The mean hospital stay in this group was3.2±0.7days (range3-6). Postoperative decreased Hb was0.67±0.34g/dL, no patient required blood transfusion.Stone composition analysis showed that, calcium oxalate stones in174patients (66.9%), infection stone (magnesium ammonium phosphate and hydroxyapatite) in50patients (19.2%), uric acid stones in24patients (9.2%), calcium phosphate in10patients (3.8%) and cystine in2patients (0.8%). KUB on postoperative1month showed that191patients were rendered stone free, stone free rate (SFR) was73.5%.69patients had residual stones ranged5-8mm, including52patients with residual stones in lower calyx, but only39patients of these69patients had the lower pole stone preoperatively.Solitary kidney was noted in31patients (11.9%) in the present study, the stone burden in solitary kidney was similar to other patients (1.77±0.54vs.1.65±0.72cm, t=0.896,P=0.371). When diverged the patients at a2cm standard according to stone burden, the proportion of patients with a stone burden larger than2cm in the two groups was similar (Χ2=3.633,P=0.057), the distribution of stones according to the proportion of lower calyx and calyx was similar in the two groups (Χ2=1.308,P=0.253及Χ2=0.040,P=0.842), and also the proportion of post-PCNL residual stones (Χ2=0.727,P=0.394). The lithotripsy time in the two groups was similar (34.4±11.7vs.32.8±13.2min, t=0.641, P=0.522), and also the operation time (46.7±11.2vs.45.2±13.1min, t=0.641, P=0.522). There was no significant difference in hospital stay between the two groups (3.5±0.9vs.3.2±0.7d, t=1.815,P=0.071). There was no significant difference in the incidence of SIRS (16.1%vs.6.99%, Χ2=3.074,P=0.080) nor SFR (70.97%vs.73.8%,Χ2=0.112,P=0.738) in the two groups. The only difference was that, the postoperative decreased Hb in solitary kidney (0.79±0.40g/dL) was significantly greater (t=2.157,P=0.032) that it (0.65±0.33g/dL) in other patients.Post-PCNL residual stone was noted in30patients (11.5%) in the present study, the stone burden in these patients was similar to other patients (1.66±0.62vs.1.67±0.71cm, t=-0.073,P=0.942). When diverged the patients at a2cm standard according to stone burden, the proportion of patients with a stone larger than2cm in the two groups was similar (Χ2=0.002, P=0.961), the distribution of stones according to the proportion of lower calyx was similar in the two groups (Χ2=0.004,P=0.950), but much more calyceal stone was noted in post-PCNL residual stone group (Χ2=11.967,P=0.001). There was no difference in the proportion of solitary kidney between the two groups (Χ2=0.727, P=0.394). There was no significant difference in the lithotripsy time similar (36.1±13.3vs.32.6±12.9min, t=1.385, P=0.167), operation time (47.8±13.7vs.45.0±12.7min, t=1.125,P=0.262) nor hospital stay (3.3±0.9vs.3.2±0.7d, t=0.288,P=0.774). The postoperative decreased hemoglobin was similar in the two groups (0.74±0.32vs.0.66±0.34g/dL, t=1.132, P=0.259). The SFR in post-PCNL residual stone group (16/30,53.3%) was significantly lower (Χ2=7.048, P=0.008) than it (175/230,76.1%) in other patients. The incidence of SIRS was similar in the two groups (10%vs.7.8%,Χ2=0.169, P=0.681).Lower calyceal stone was noted in88patients (33.8%) in the present study, the stone burden in solitary kidney was similar to other patients (1.57±0.65vs.1.72±0.72cm, t=-1.647, P=0.101). When diverged the patients at a2cm standard according to stone burden, the proportion of patients with a stone burden larger than2cm was more frequently noted in lower calyceal stone group (Χ2=27.082,P<0.001), and also the solitary kidney (Χ2=4.962,P=0.026) and post-PCNL residual stones (Χ2=32.264,P<0.001). The lithotripsy time in the two groups was similar (33.6±13.6vs.32.7±12.7min, t=0.531, P=0.596), and also the operation time (45.9±13.6vs.45.1±12.5min, t=0.480, P=0.631). There was no significant difference in Hb decreased (0.66±0.32vs.0.67±0.35g/dL, t=-0.189, P=0.850) nor hospital stay (3.16±0.62vs.3.27±0.77d, t=-1.141, P=0.255) between the two groups. Lower calyceal stone group had a lower SFR (55.7%vs.82.6%,Χ2=11.595, P<0.001). There was no significant difference in the incidence of SIRS (5.7%vs.9.3%,Χ2=1.028, P=0.311).Irrigation pump was used in142patients and syringe injection was used in118patients. The irrigation flow rate from pump was significantly higher than it from syringe injection (48.6±9.6vs.32.8±11.4ml/min, t=12.041, P<0.001). The intraoperative irrigation volume in pump group (1582.1±770.0ml) was significantly higher (t=4.419, P<0.001) than it (1165.1±742.2ml) in syringe group. The stone burden in the two groups was similar (1.69±0.66vs.1.63±0.74cm, t=0.662, P=0.509), there was no significant difference in the lithotripsy time (32.1±13.1vs.34.0±12.8min, t=-1.153, P=0.250), operation time (44.4±13.0vs.46.6±12.6min, t=-1.375, P=0.170) nor hospital stay (3.25±0.76vs.3.20±0.69d, t=0.554, P=0.580) between the two groups. The postoperative decreased hemoglobin was similar in the two groups (0.70±0.35vs.0.62±0.32g/dL, t=0.257, P=0.797). There was no significance in the postoperative SIRS rate (Χ2=0.490, P=0.484).On postoperative one month,191patients were rendered stone free, the stone free rate (SFR) was73.5%. These191patients were categorized as stone free group, the remaining69patients were categorized as non-stone free group. The mean stone burden in non-stone free group (2.19±0.71cm) was significantly larger (t=8.053, P<0.001) than it (1.48±0.59cm) in stone free group.79patients had a stone burden larger than2cm, the SFR in these patients (38/79,48.1%)was significantly lower (Χ2=37.436,P<0.001) than it (153/181,84.5%)in patients with a stone burden less than2m. Lower calyceal stone was noted in88patients, the SFR (49/88,55.7%) was significantly lower(Χ2=21.570, P<0.001) than it (142/172,82.6%) in other patients (upper calyx, middle calyx, renal pelvis, upper ureter).169cases had the stone located in renal calyx, the SFR in these169patients (110/169,65.1%) was significantly lower (Χ2=17.363, P<0.001) than it (81/91,89.0%) in those patients with stones located in renal pelvic and upper ureter. Post-PCNL residual stones was noted in30patients, the SFR in these30patients (16/30,53.3%) was significantly lower (Χ2=7.048, P=0.008) than it (175/230,76.1%) in other patients. Preoperative urinary tract infection (UTI) was noted in47patients, the SFR in these patients (28/47,59.6%) was lower (Χ2=5.615, P=0.017) than it (163/213,76.5%) in those patients without preoperative UTI. Infection stone was noted in50patients from postoperative stone composition analysis, the SFR in these patients (29/50,58%) was lower (Χ2=7.591, P=0.006) than it (162/210,77.1%) in patients with other stone composition. The irrigation flow rate in stone free group (45.0±12.1ml/min) was significantly higher (t=2.680, P=0.008) than it (40.1±13.2ml/min) in non-stone free group, and also the intraoperative irrigation volume (1912.4±845.5vs.1205.2±670.0ml, t=6.989,P<0.001). The lithotripsy time in non-stone free group (42.2±13.6min) was significantly longer (t=7.575,P<0.001) than it (29.7±11.1min) in stone free group, and also the operation time (53.1±13.8vs.42.5±11.3min, t=6.285, P<0.001).The above Chi-square test and t-test showed the potential influence factors of SFR, included stone burden, stone≥2cm, lower calyceal stone, calyceal stone, post-PCNL residual stone, preoperative UTI, irrigation flow rate, irrigation volume, infection stone, lithotripsy time and operation time. Taking into the previous studies and clinical experience, the solitary kidney was included. At last, nine covariates were entered in the logistic regression analysis. Four covariates were identified from the logistic regression analysis, included:stone burden (OR=8.636,95%CI:4.594-16.236), lower calyceal stone (OR=9.892,95%CI:4.463-21.923), post-PCNL residual stone (OR=4.632,95%CI:1.715-12.512) and infection stone (OR=2.302,95%CI:0.999-5.305).Postoperative SIRS was noted in21patients (8.1%), these21patients were categorized as SIRS group, and the remaining239patients were categorized as non-SIRS group. The incidence of SIRS in female patients (18/157,11.5%) was significantly higher (Χ2=20.295,P<0.001) than it in male patients(3/103,2.9%). The stone burden in SIRS group (2.13±0.97cm) was significantly larger (t=3.225, P=0.001) than non-SIRS group(1.63±0.66cm).79patients had a stone burden larger than2cm, the incidence of SIRS (9/79,11.4%) in these patients was similar (Χ2=1.680, P=0.195) to it (12/181,6.6%) in the patients had a stone burden less than2cm. Lower calyceal stones was noted in88patients, the incidence of SIRS (5/88,5.7%) in patients with lower calyceal stones was similar (Χ2=1.028, P=0.311) to it (16/172,9.3%) in those patients with stones in other calyx.169patients had the stones located in renal calyx, the incidence of SIRS in these169patients (16/169,9.5%) was similar (Χ2=1.258, P=0.262) to it (5/91,5.5%) in those patients with stones located in renal pelvis and upper ureter. Post-PCNL residual stones was noted in30patients, the incidence of SIRS in these30patients (3/30,10%) was similar (Χ2=0.169, P=0.681) to it (18/230, 7.8%) in other patients. Solitary kidney was noted in31patients, there was no significant difference (Χ2=3.074, P=0.080) in the incidence of SIRS in these patients (5/31,16.1%) when compared to patients with bilateral kidney (16/229,7.0%).12/14Fr ureteral access sheath was used in127patients, the incidence of SIRS in these patients (10/127,7.9%) had no significant difference (Χ2=0.014,P=0.907) when compared it (11/133,8.3%) to133patients who used14/16Fr ureteral access sheath. Pump irrigation was performed in142patients, the incidence of SIRS in these patients (13/142,9.2%) had no significant difference (Χ2=0.490, P=0.484) when compared to it (8/118,6.8%) in118patients with syringe irrigation. The intraoperative irrigation flow rate in SIRS group (59.1±10.9ml/min) was significantly higher (t=7.017,P<0.001) than it (39.9±12.1ml/min) in non-SIRS group, and the total irrigation volume in SIRS group (2168.3±828.0ml) was significantly higher (t=4.935, P<0.001) than it (1324.7±774.2ml) in non-SIRS group. Preoperative urinary tract infection (UTI) was noted in47patients, the incidence of SIRS in these patients (6/47,12.8%) was similar (Χ2Ξ1.699, P=0.192) to it (15/213,7.0%) in those patients without preoperative UTI. Infection stone was noted in50patients from postoperative stone composition analysis, the incidence of SIRS in these patients (7/50,14%) was similar (Χ2=2.925, P=0.087) to it (14/210,6.7%) in patients with other stone composition. There was no difference in the lithotripsy time (36.6±11.9vs.32.7±13.1min, t=1.322, P=0.187) nor in the operation time (48.0±11.6vs.45.1±13.0min, t=0.967, P=0.334) in both groups. The hospital stay in SIRS group (5.57±0.51d) was significantly longer (t=54.200, P<0.001) than it (3.03±0.16d) in non-SIRS group. The postoperative decreased hemoglobin in SIRS group (1.47±0.23g/dL) was significantly higher (1=15.450, P<0.001) than it (0.60±0.25g/dL) in non-SIRS group.The above Chi-square test and t test demonstrated the potential risk factors for SIRS after RIRS, including female gender, stone burden, irrigation flow rate, irrigation volume, the solitary kidney, preoperative UTI, lithotripsy time, infection stone were included, when considered the previous studies and clinical experience, irrigation method and the access sheath were also entered in the logistic regression analysis. Six variables were entered in the equation from logistic regression analysis, included stone size (OR=2.494,95%CI:0.865-7.190), irrigation flow rate (OR=1.198,95%CI:1.121-1.279), lithotripsy time (OR=0.953,95%CI:0.888-1.022), infection stone (OR=4.140,95%CI:1.110-15.448), irrigation method (OR=0.108,95%CI:0.023-0.515) and small-caliber access sheath (OR=0.288,95%CI:0.081-1.026).Conclusions:Flexible ureteroscopic lithotripsy was a well established technique in the treatment of upper urinary tract stones, with high stone clearance rate and few complications. With the advancement in flexible ureteroscope and other equipment, modern flexible ureteroscope has better visualization and the bend ability. It can enter into much more complex space, and with the increased clinical application of this technique, the accumulated clinical experience of flexible ureteroscopic lithotripsy, the indication for RIRS has changed gradually and became much wider. It was capable of handling stones with larger burden, such as kidney stones≥2cm, as well as some complex cases, including solitary kidney, spinal deformity, horseshoe kidney, calyceal diverticular calculi, etc., with a high SFR and low complication rate.Stone burden and location was the most important influence factors to SFR of RIRS. It was time consuming in the procedure of stone fragmentation with Ho:YAG laser, the lithotripsy time prolonged significantly when the stone burden increased, while the operation time should be seriously controlled. On the other hand, the stone fragments would hamper the further procedure for lithotripsy, and thus decreased the SFR. The anatomy of renal collecting system had a great effect on the SFR after RIRS, including the flexible ureteroscope can not get to the lower calyceal stone, and the stone fragments from other calyx always deposited in the lower calyx where the fragments have to overcome the ravine effect before the passage from renal calyx into ureter. Post-PCNL residual stones were likely to be encapsulated in some atretic calyx, and it’s hard to get in the RIRS procedure, thus the SFR decreased.There was no significance in the stone burden nor location between the patients with solitary kidney and other patients with bilateral kidney, the SFR and incidence of SIRS was similar in these patients, whereas the Hb decreased much more in the patients with solitary kidney postoperatively.Pump could provide irrigation with higher flow rate than syringe, which would increase the renal pelvic pressure. Irrigation method and irrigation flow rate was risk factors for SIRS after RIRS. The irrigation with high flow rate could provide better visualization, but the SFR was not improved, thus irrigation with low pressure and low flow rate was recommended.There were many potential risk factors for SIRS after RIRS, including female sex, irrigation method, small size access sheath, infection stone, stone burden, irrigation flow rate, lithotripsy time, etc. Bacteria and endotoxin was noted in stones, especially in infectious stones, and was released into the irrigation fluid when being crushed, it was the resource of SIRS. Pump provided irrigation with high pressure and high flow rate can bring good visualization and also a high renal pelvic pressure, prompt backflow and absorption of irrigation fluid. Small-caliber ureteral access sheath could bring inadequate drainage and also increase the renal pelvic pressure. Large stone burden would prolong the operation time, and result in the absorption of irrigation fluid get to a certain threshold eventually causing SIRS. The elder female patients were more likely to have a UTI and infection stone, and also the SIRS after RIRS. Preoperative anti-infective therapy with the sensitivity antibiotics, irrigation with low pressure and low flow rare, drainage with large-caliber ureteral access sheath, a seriously controlled operation time was recommended to decrease the incidence of SIRS after RIRS. For elder female patients, patients with infection stone and other high-risk factors, special attention should be paid to control the operation time and irrigation.