Flexible ureteroscopy:Technological advancements,current indications and outcomes in the treatment of urolithiasis

Division of Urology,Department of Surgery,Schulich School of Medicine&Dentistry,Western University,London,Ontario,Canada

REVIEW

Flexible ureteroscopy:Technological advancements,current indications and outcomes in the treatment of urolithiasis

Husain Alenezi,John D.Denstedt*

Division of Urology,Department of Surgery,Schulich School of Medicine&Dentistry,Western University,London,Ontario,Canada

The last 3 decades have witnessed great improvements in the technology and clinical applications of many minimally invasive procedures in the urological f i eld.Flexible ureteroscopy(fURS)has advanced considerably to become a widely utilized diagnostic and therapeutic tool for multiple upper urinary tract pathologies.The most common indication for fURS is the treatment of upper urinary tract stones with the aid of Holmium:Yttrium Aluminium Garnet(YAG)laser lithotripsy.Advancements in endoscope technologies and operative techniques have lead to a broader application of fURS in the management of urolithiasis to include larger and more complex stones.fURS has proved to be an effective and safe procedure with few contraindications.Continued progression in fURS may increase its clinical applicability and supplant other procedures as the f i rst line treatment option for urolithiasis.

Flexible ureteroscopy;

Urolithiasis;

Renal stone;

Endoscopy

1.Introduction

Flexible ureteroscopy(fURS)has been through signif i cant technological and technical advancements in the previous 3 decades,resulting in the widespread utilization of fURS in the treatment of a variety of upper urinary tract pathologies,mainly urolithiasis.

Herein,we discuss the major technologic advances in fURS,its current role and outcomes in the treatment of urolithiasis.

2.History and technological advancements of fURS

Since the f i rst report of fURS by Marshall in 1964[1],major developmental milestones in the technology of f l exibleureteroscopes have led to the current relative ease of clinical application together with a high success rate and low associated morbidity.In 1980’s,fURS was signif i cantly improved after the development of f i berotic light-bundles together with endoscope tip-def l ection mechanisms(passive or active)and the incorporation of an irrigation working-channel that allowed its use as a therapeutic tool [2].The next substantial technological advancement was in 1994,after the successful therapeutic utilization of a miniaturized f l exible ureteroscope,with a tip diameter of 7.5 Fr and an adequate working-channel of 3.6 Fr[3].The miniaturized f l exible ureteroscope enabled active 2-way def l ection with secondary passive def l ection at the shaft, thus increasing endoscope maneuverability and clinical applicability.

Concurrently,the successful introduction of the Holmium:Yttrium Aluminium Garnet(YAG)laser as a f l exible intracorporeal lithotripter with a high safety margin lead to an increased interest in the treatment of urolithiasis in a retrograde fashion[4].In 2001,a f l exible ureteroscope with active 2-way exaggerated def l ection(up to 270?)was introduced to the market and improved the ability to navigate the entire pelvicaliceal system[5].The durability off l exible endoscopessubsequentlyimprovedandit became possible to perform up to 50 therapeutic procedures before any maintenance was necessary[6].The revolution of endoscope technology continued with the introduction of digital f l exible ureteroscopes in 2006,which improved the image quality and resulted in lighter-weight equipment due to the integration of the light-cable and camera within the endoscope.Unfortunately,digital f l exible ureteroscopes had a larger diameter than the conventional f i beroptic f l exible counterparts and their use was associated with increased need for placement of a ureteral access sheath(UAS)[7],which is associated with higher risk of ureteral injuries[8].However,further development led to the introduction of smaller caliber digital f l exible ureteroscopes comparable to the previous conventional endoscopes[9].

Advancementsandinnovationsintechnologyhave continued to progress with the goal of designing optimal small diameter endoscopes,improved image quality and maneuvering abilities combined with lasting durability.In 2010,Sun et al.[10]reported the f i rst combined rigid and fl exible ureteroscope“the Sun’s ureteroscope”.The authors treated 175 patients with intrarenal stones using this novel ureteroscope,which has a retractable rigid shaft and fl exible tip that enables the operator to treat ureteral and intrarenal stones eff i ciently without the need to exchange from one endoscope to another.The Sun’s ureteroscope resulted in short operative time with an overall stone-free rate(SFR)of 83%.In 2008,Desai et al.[11]reported their feasibility study using a new innovative robotic f l exible ureteroscope in an animal model,that was followed by a report on their encouraging clinical experience in treating urolithiasis using the same robotic f l exible device[12].In 2014 the initial experience with a new robotic platform for fURS was reported[13].Seven experienced surgeons examined the new robotic platform in treating 81 patients with urolithiasis.The initial experience was successful and was associated with improved ergonomics in comparison to conventional counterparts.

3.The current role of fURS in the treatment of urolithiasis

3.1.Treatment of intrarenal stones less than 2 cm

With the continued advancements of technology and increasing experience gained by urologists in ureteroscopic skills,fURS has become an integral aspect of the armamentarium in treating intrarenal stones less than 2 cm in diameter.In the previous iteration of the European guidelines on the management of urolithiasis,fURS was recommended as a second-line treatment for stones less than 2 cm after shock wave lithotripsy(SWL),however in the recent revision of the guidelines,both fURS and SWL were recommended as f i rst-line management options especially for stones measuring between 11 and 20 mm[14],ref l ecting the increasing success in treating intrarenal stones in a retrograde fashion.

In 1990’s,the initial reports on successful management of urolithiasis with fURS came from high-volume experienced centers[15,16].Grasso and Ficazzola[16]achieved an SFR of 94%and 95%for intrarenal stones measuring less than or equal to 10 mm and 11e20 mm,respectively with fURS and laser lithotripsy.Sofer et al.[15]reported their experience with a large cohort of patients including 598 patients who were treated with ureteroscopy(URS)and laser lithotripsy from 1993 till 1999.The average stone size was 11.3 mm and 56 of the included patients had intrarenal stones treated with fURS.The authors achieved an SFR of 84%for intrarenal stones with a low overall complication rate of 4%.

Comparative studies of fURS,SWL and/or percutaneous nephrolithotripsy(PCNL)showed an advantage in the success rate of fURS over SWL[17],while fURS had a comparablesuccess-rate to PCNL(or Miniperc)with lower associated morbidity in the treatment of intrarenal stones [18e20].

It is anticipated that fURS will play a more important role in the management of symptomatic intrarenal stones in the near future and fURS may signif i cantly supplant SWL as the modality of choice for treating intrarenal stones less than 2 cm.

3.2.Treatment of intrarenal stones greater than 2 cm

PCNL is the gold standard for large renal stones measuring 2 cm or greater as de fi ned by American Urological Association(AUA)and European Urological Association(EUA) guidelines[14,21].PCNL however can be associated with signi fi cant complications,longer hospital stay and convalescence.Therefore,a less morbid option to treat large renal stones would be especially advantageous to high-risk patients.

Early reports on the use of fURS in the treatment of large renal stones appeared in the 1990’s,when Aso et al. [22]described their experience in treating 34 patients with staghorn renal stones.At that time,the only available fl exible intracorporeal lithotripter was electrohydraulic based,which resulted in a high complication rate rendering fURS an unacceptable management option for large renalstones.Efforts to f i nd a safe alternative to PCNL continued and a trial to combine fURS with SWL to treat staghorn stones was successful in fragmenting 21 out of 27 stones [23],patients however required up to 26 SWL sessions (mean of 8.4 procedures),leading to concerns about shock wave bioeffects on the renal parenchyma and costs.With further advancement of endoscope and Holmium:YAG laser lithotripter technology,fURS has re-emerged as a therapeutic option for large renal stones.Grasso et al.[24] treated 45 large intrarenal stones using fURS and Holmium:YAG laser lithotripsy.They included patients with stones greater than 2 cm in a population with medical comorbidities that precluded treatment with PCNL.The SFR, def i ned as fragments less than 2 mm,was encouraging at 76%after the f i rst treatment and re-treatment with fURS increased the f i nal SFR to 91%.The high success rate reported by Grasso et al.[24]was accompanied by a low postoperative complication rate of 6.2%.Recently,a metaanalysis by Aboumarzouk et al.[25]included nine primary studies reporting on 445 patients(460 renal units)diagnosed with large intrarenal stones and treated with fURS and laser lithotripsy.The average SFR was 93.7%(range 77.0%e96.7%)after an average of 1.6 procedures per patient for treatment stones with of a mean size of 2.5 cm. That high success rate,comparable to PCNL results,was associated with a complication rate of 10.1%.Major complications including steinstrasse,subcapsular hematoma, obstructivepyelonephritis,cerebrovascularaccident, acute prostatitis and hematuria leading to clot retention were noted in 5.3%patients,while 4.8%of patients experienced minor complications mostly self limiting hematuria and postoperative fever.However,a subgroup analysis revealed no major complications in the group of patients with a 2e3 cm stone.Further reports on fURS for the treatment of large renal stones achieved similar high SFR after multiple procedures[26,27].Concurrent use of UAS, which facilitated multiple re-entries of the endoscope and improved visibility,was noted as a factor contributing to improved outcomes.

Akman et al.[28]pair-matched and analyzed 34 patients with 2e4 cm renal stones treated with fURS with patients treatedwithPCNL.Patientswerematchedondemographics(age,gender and body mass index),renal anomalies(solitary kidney and degree of hydronephrosis), stone characteristics(size,number and location)and history of previous interventions(SWL and open surgery).The initial stone-free status was signif i cantly higher in favor of PCNL(73.5%and 91.2%for fURS and PCNL,respectively), but the difference lost its signif i cance after the second fURS procedures with a f i nal SFR of 88.2%.PCNL was found to be statistically better in terms of shorter mean operative time,but with a longer hospital stay than fURS.There was no statistical difference in the associated complications after both procedures,although two patients required blood transfusions after PCNL.However,fURS was found to be signif i cantly inferior in treating intrarenal stones greater than 2 cm compared to miniperc(18 Fr tract)in another matched-pair analysis[29].The success rate was only 43.4% after the f i rst fURS procedure.

In most series,the number of procedures required to achieve a successful outcome is the main concern in using fURS to treat large intrarenal stones[30].This is offset by the low associated complication rate,making fURS a valid alternative to PCNL especially in high-risk patients.

fURS has also been described as a successful adjunct to PCNL in treating complex renal stones in order to reduce the number of tracts and associated complications[31e34]. fURS was performed either simultaneously with or in a staged fashion from PCNL resulting in results equal to conventional PCNL.

3.3.Treatment of lower pole stones

Treatment of lower pole renal stones is an ongoing dilemma due to the dependent position of the lower calyces limiting spontaneous passage of stone fragments after SWL[35]. Additionally,the anatomy of the lower pole calices makes them less accessible by f l exible ureteroscopes than mid or upper calices.In 1999,Grasso and Ficazzola[16]failed to access the lower pole by fURS in 7%of their patients using an early generation ureteroscope with limited active def l ection ability,yet they achieved a high success rate in treating 93%of the cohort with an SFR of 94%and 95%for stones greater than 1 cm and less than 1 cm,respectively. Researchers have tried to determine the anatomical factors associated with failure to access the lower pole in a retrograde fashion by fURS[36e38].An acute infundibulopelvic angle(<30?)and a long infundibular length(>3 cm) were found to be associated with lower SFR in treating lower calyceal stones,while there was no effect exerted by the infundibular width[36e38].However,after the development of modern endoscopes with extended active def l ection abilities and advancement of operative techniques[39],accessibility of lower pole stones to fURS has improved.Stone repositioning to a more accessible calyx using tipless Nitinol baskets before laser lithotripsy is a technique that has improved the success rate of fURS in treating lower pole stones.Baskets result in minimal loss of endoscope active def l ection and irrigation f l ow in comparison to the smallest laser f i ber facilitating successful access to the lower pole with better visibility[40].Schuster et al. [41]found an improved SFR after stone repositioning in comparison to in situ lithotripsy of lower pole stones.The difference was signif i cant especially for stones greater than 1 cm,with SFR of 100%and 29%for stone repositioning and in situ lithotripsy,respectively.As a result of technological and technical advancements,some authors have demonstrated equivalent SFR achieved after treating lower pole stones compared to stones residing in other calyces with fURS[42,43].

Although fURS had no advantage over SWL in treating lower pole stones?1 cm in a randomized control trial conducted by the Lower Pole Study Group[44].More recent studies have demonstrated advantages in favor of fURS [45,46].In 2012,El-Nahas and colleagues[45]analyzed a matched-pair group of patients with 10e20 mm lower pole stones treated with fURS or SWL.fURS had a statistically signif i cant higher SFR(86.5%vs.67.7%for SWL)and lower retreatment rate(8%vs.60%for SWL group).A recent prospective randomized trial by Kumar et al.[46]included 195 patients with radio-opaque lower pole stones treated by fURS or SWL.The mean stone size was comparable in the two groups(12 mm).Both treatment groups had comparable SFR at 3 months,but the retreatment rate wassignif i cantly higher for the SWL patients(61.1%vs.11.1%for fURS).The additional retreatment rate would impact the associated costs of both procedures.

fURS was also retrospectively compared to PCNL(and miniperc)in the treatment of lower pole stones less than 20 mm[47,48].The success rate was similar in both groups with no difference in associated complications.PCNL and miniperc were associated with shorter operative time, higher f l uoroscopy time and longer hospital stay in comparison to fURS.

fURS seems poised to play an important role in the management of lower pole renal stones less than 2 cm.

3.4.Proximal ureteral stones

SWL and fURS account for the vast majority of interventions for proximal ureteral stones worldwide.Both procedures are accepted as f i rst line treatment option for proximal ureteral stones according to the latest EAU guidelines[14]. Although a less invasive procedure than fURS,SWL has been associated with a lower success rate and higher retreatment rate in comparison to fURS for ureteral stones[49]. Additionally,Pace et al.[50]demonstrated a signif i cant decrease in the SFR with retreatment of ureteral stones by SWL after a failed initial treatment.On the other hand, early reports on fURS and laser lithotripsy for the treatment proximal ureteral stones demonstrated a high SFR of more than 95%[15,24].The high success rate of fURS in treatmentofproximalureteralstoneswasrecentlyredemonstrated in a prospective,multi-institutional study that included 71 patients with solitary proximal ureteral stones[51],with an overall SFR of 95%and SFR of 100%for stones less than 1 cm.In a systematic review by Kijvikai et al.[52]to examine the outcomes of SWL and URS in the management of proximal ureteral stones less than or equal to 2 cm,a signif i cantly better outcome was found after URS for stones over 10 mm.However,the review included heterogeneous data from studies of both semi-rigid URS and fURS.

Therefore,fURS may be considered a competitive option to treat proximal ureteral stones when compared to SWL, especially in treating larger stone burdens or SWL-refractory stones.

4.Stones in special situations

4.1.Treatment of urolithiasis during pregnancy

Despite the low incidence of urolithiasis during pregnancy, it is the most common non-obstetric cause for hospital admission[53].In a population-based retrospective cohort study,Swartz et al.[54]found that pregnant women admitted to hospital with urolithiasis have an increased risk of preterm delivery in comparison to pregnant women admitted due to other non-obstetric causes.There was no signif i cant difference in obstetric complications between pregnant patients who underwent intervention for nephrolithiasis compared to patients who did not[54].

Up to 20%of pregnant women with nephrolithiasis may require procedural intervention[53].Temporizing measures with deferred def i nitive treatment have a limited role in the management of urolithiasis during pregnancy,especially during the f i rst two trimesters,due to the associated increased encrustation of ureteric stents and blockage of nephrostomy tubes with subsequent need for frequent exchanges[55].Additionally,SWL is contraindicated during pregnancy due to potential harmful effects on the developing fetus[14].Thus,URS poised to be an attractive def i nitive option to treat urolithiasis during pregnancy[56].

In 1988,Rittenberg and Bagley[57]were the f i rst to report performing fURS in two pregnant women.Watterson et al.[58]treated eight pregnant women with urolithiasis by URS(semi-rigid and f l exible)using the Holmium:YAG laser under general anesthesia and achieved an 89%SFR with no postoperative urologic or obstetric complications. Ureteral dilatation was not required in their series,however six patients had pre-stented ureters[58].While Lifshitz and Lingeman[59]had to dilate the ureteric orif i ces in four patients to facilitate URS,they performed fURS in the majority of patients under spinal anesthesia with no major postoperative complications.

Semins et al.[60]performed a systematic review examining the safety of URS during pregnancy.The authors found a low rate of postoperative complications in 108 patients.Most of the reported complications were Clavien level 1 and 2,and there was no signif i cant difference in ureteral injury or urinary tract infection rates in comparison to a multinational meta-analysis of URS in non-pregnant women.

Although large cohort studies are not available in the literature,fURS seems to be a safe def i nitive method for treatment of urolithiasis during pregnancy with a low rate of major complications.

4.2.Treatment of urolithiasis in children

In the recent years,the vast majority of pediatric urolithiasis are managed by minimally invasive endourologic procedures such as SWL,URS and PCNL[61].Similar to the adult population,the shift from open surgery to endourologic management was possible due to advancement of technology and miniaturization of endourologic instruments.Previously, concerns over instrument associated intraoperative complications such as ureteral perforation and vesicoureteral ref l ux lead to the late adoption of URS in the treatment of pediatric stone disease.While currently,URS(both semi-rigid and f l exible)is playing an important role in the management of upper urinary tract stones in children and is now feasible even in preschool age children[62].

Tan et al.[63]published one of the f i rst reports on the management of pediatric urolithiasis by URS that included six children who were treated by fURS successfully.In 2008,Kim et al.[64]had the largest cohort of pediatric patients treated by fURS and Holmium:YAG laser lithotripsy.The authors performed 170 procedures to treat 167 children suffering from intrarenal and ureteral stones, with 100%and 97%stone clearance for stones less than 10 mm and greater than 10 mm,respectively.The mean age of their patients was 62.4 months with a mean stone size of 6.12 mm(range 3e24 mm).Active ureteral dilation was avoided,but initial retrograde access was not possible in 57%of the children who were subsequently stented for 1e2 weeks followed by successful fURS.The authorsstated that no major intraoperative or postoperative complications were encountered with a mean follow-up of 19.7 months.Likewise,fURS with laser lithotripsy was found to be a safe and effective procedure in treating pediatric intrarenal stones by a systematic review that included 282 children from six studies[65].With a total reported complication rate of 12.4%,the vast majority of the complications were within Clavien grade 1 or 2.Only six patients had Clavien grade 3 complications;f i ve ureteral perforations and one extravasation,which were related to UAS insertion or active balloon dilatation of the ureter[62,66].The mean SFR reported in the systematic review was 85.5%(range 58%e93%)after one fURS procedure,demonstrating the effectiveness of fURS in children. Despite the apparent need for pre-stenting in a signif icant percentage of children prior to achieving safe retrograde ureteroscopic access,Mokhless et al.[67]were able to proceed with initial URS in almost all of the included children by starting with the semi-rigid ureteroscope to hydro-dilate the ureter before inserting the f l exible ureteroscope.They prospectively compared the outcomes of retrograde intrarenal surgery(RIRS)to SWL in the treatment of pediatric renal stones after randomly allocating 60 children(mean age of 2.4 years)with 10e20 mm stones into one of the two treatment arms.RIRS was found to have a better initial SFR of 86.6%in comparison to 70%after SWL, however at 3 months the SFR was comparable at 96.6%and 93.3%post RIRS and SWL,respectively.Furthermore,in a multi-center comparative analysis of the outcomes of pediatric patients with renal stones 10e30 mm in size treated with miniperc(n Z 106)or RIRS(n Z 95)[68],stone-free status was comparable at 84%and 86%for RIRS and miniperc,respectively.However,minor complication rates were 8.4%for RIRS and 17%for miniperc,with 6%transfusion rate after miniperc in comparison to no blood transfusion post RIRS.Moreover,the analysis showed favorable results to RIRS in terms of shorter f l uoroscopy exposure,operative time and hospital stay,compared to miniperc.

4.3.Treatment of urolithiasis with renal anomalies

The management of urolithiasis in patients with anomalous kidneys imparts a special challenge to the treating urologist [69],due to the associated abnormal vascular supply,pelvicaliceal anatomic abnormalities such as ureteropelvic obstruction,andtheunusualrelationtosurrounding structures.

SWL has a high failure rate in patients with renal anomalies due to either the impaired urinary drainage associated with the anomaly or diff i culty targeting the stone due to overlying bones[69].More invasive procedures such as PCNL and laparoscopy can be associated with increased risk of iatrogenic injury to adjacent organs and vascular structures[69].Thus,fURS offers a minimally invasive therapeutic option for urolithiasis in patients with renal anomalies that can be performed as a day-procedure with low rate of complications.

Horseshoe kidney(HSK)is one of the common renal anomalies with an incidence up to 1/400 live births and is associated with urolithiasis in 20%of the cases[70].Weizer et al.[71]were the f i rst to report the successful treatment of renal stones in patients with HSK with fURS.They achieved a 75%SFR after performing fURS with Holmium:YAG laser lithotripsy and nitinol baskets in four patients with HSK and four patients with pelvic ectopic kidneys(PEK).In 2010,Molimard and colleagues[72]published their retrospective experience in treating 17 HSK patients with fURS and laser lithotripsy.Of the 17 included patients,eight had SWL refractory stones and four patients failed previous PCNL.Stone repositioning was required in nine patients with lower pole stones before laser lithotripsy.Their reported success rate,def i ned as stone-free status or residual stone less than 3 mm,was 88.2%after 1.5 procedures for the treatment of stones measuring 7e35 mm(average of 16 mm),with no major complications encountered.More recently,the Turkish experience was reported in treating 20 patients with a mean stone size of 17.8 mm in HSK by fURS[70].Treatment was successful in 70%of patients who were rendered either completely stone free or with insignif i cant residual fragments less than 4 mm.Postoperative complication rate of 25%consisted of only minor Clavien grade 1 and 2 complications that included fever and selflimiting hematuria.

While Weizer et al.[71]had a 75%success rate in treating intrarenal stones within 4 PEK patients by fURS, Bozkurt et al.[73]experienced 84.6%successful fURS procedures in their retrospective multi-center report of 26 patients with stone bearing PEK.The mean stone size was 17 mm(range of 10e28 mm)with nine SWL refractory stones.Stone lithotripsy was accomplished by Holmium:YAG laser lithotripsy while stone repositioning was performedonlyifneeded.Theauthorsreported19.2% postoperative complication rate with two patients requiring insertion of ureteral stents due to persistent renal colic.

The role of fURS and laser lithotripsy in the treatment of stone bearing calyceal diverticula was perhaps more studied than other pelvicaliceal system anomalies.In 2010, Sejiny et al.[74]reported the largest retrospective cohort at that time describing their experience in treating symptomatic stone bearing calyceal diverticula with fURS and laser lithotripsy.They treated 36 symptomatic patients with an average stone size of 11.4 mm(5e22 mm),with 30 stones that had failed previous SWL.In that report,the authors described“The blue-test”,a novel technique to identify the diverticular neck in diff i cult cases using retrograde Methylene blue injection.After identif i cation of the diverticular neck,careful incision of the neck was carried out to allow the passage of the f l exible ureteroscope into the diverticulum.Neck incision was performed in 30 patients using high frequency and low energy laser settings(10 Hz and 0.8 J).The authors achieved 55.3%SFR with an additional 26.3%of patients having insignif i cant residual fragments less than 4 mm.Ninety percent of patients were rendered symptom-free making the results comparable to those after PCNL in treating calyceal diverticula stones,yet with lower morbidity,as there were no major complications observed after the fURS.Koopman and Fuchs[75]successfully identif i ed the neck or the stenotic infundibular segment in 95%of 108 symptomatic patients due to intrarenal stones residing in caliceal diverticula or beyond an infundibular stenosis.They were able to dilate or incise the stenotic segment in 94%of the patients after successfully coiling a guide-wire into the diverticulum ordilated calyx.fURS with laser lithotripsy and nitinol baskets were used in patients with less than 2 cm stones,while patients with stones 2 cm and larger were treated using a combined approach of fURS,laser lithotripsy with nitinol baskets and SWL.The SFR was 90%and 75%for stones less than 2 cm and 2 cm and greater,respectively.Both Sejiny et al.[74]and Koopman and Fuchs[75]noticed greater diff i culty and less satisfactory results associated with lower pole stones in comparison to other calyces.

4.4.Treatment of urolithiasis in anticoagulated patients

Patients with bleeding diathesis or on anticoagulation medications cannot be treated with PCNL or SWL due to the associated risk of signif i cant bleeding.While fURS has been proven to be safe and eff i cient when used together with the Holmium:YAG laser lithotripsy in the treatment of urolithiasis in patients with different types of bleeding diatheses or anticoagulants[76e79].Watterson et al.[76]reviewed the charts of 25 patients with bleeding diathesis who were managed by ureteroscopic procedures for the treatment of urolithiasis.The bleeding diathesis consisted of warfarin administration in 17 patients,thrombocytopenia in four, liver end-stage disease in three and von Willebrand’s disease in one.Ninteen procedures were performed mainly using fURS and the Holmium:YAG laser lithotripsy,while electrohydraulic lithotripsy was used earlier in the study in two patients.The authors found only one major complication,retroperitoneal bleeding,in a patient who was concomitantly treated by electrohydraulic lithotripsy while there was no complications in the rest of the patients treated with the aid of the Holmium:YAG laser lithotripsy. More recently,a pair-matched analysis was performed by Turna et al.[78]to examine the safety of fURS and Holmium:YAG laser lithotripsy in treating intrarenal stones in anticoagulatedpatients.Althoughtheanticoagulation group was signif i cantly older and had a greater American Society of Anesthesiologists Score,there was no difference in the intraoperative and postoperative complications with comparable SFR rates.

供試植物材料共8個，分皮、裸兩組，皮燕麥以紅旗2號為對照，參試品系是gp005、gp012、gp030；裸燕麥以品5號為對照，參試品系是gl011、gl001、gl016。對照為光照敏感品種。供試材料均由張家口市農(nóng)科院提供。

4.5.Treatment of urolithiasis in obese patients

Obesity is a common prevalent disease of the Western world that is associated with higher risk of urolithiasis.Yet obesity can negatively affect the treatment options for upper tract urinary stones.The success rate of SWL is decreased with obesity and greater skin-stone distance, while PCNL becomes more complicated in obese patients due to the longer tracts and increased risk of anesthetic complications associated with prone positioning.The eff icacy of fURS in the treatment of upper tract stones in obese and morbidly obese patients has been well studied[80e86], and the SFR and associated complications of fURS were not affected by the patient’s body mass index[84e86].

5.Contraindications and complications of fURS

Apart from general considerations,such as anesthetic contraindications and untreated urinary tract infection, fURS has no speci fi c contraindication[14].fURS can be performed in virtually every patient and it is especially suitable in situations when PCNL and SWL are either contraindicated or unsuitable.

The continually developing endoscope technology and the associated widespread utilization of fURS[87]have led to increased experience and improved skills in performing the procedure with low associated morbidity[88].In the prospective CROES study,which included 11,885 patients from 114 centers in 32 different countries,15%of the included patients(n Z 1781)underwent fURS alone,while another 10.7%had combined semirigid and fURS for the treatment of their stones[89].The overall postoperative complication rate was as low as 3.5%and the majority of the complications were Clavien grade 1 or 2(2.8%).Only 0.2%of patients required blood transfusion,and there were fi ve mortalities in the 30-day postoperative period due to sepsis,lung embolism,multi-organ dysfunction and cardiac causes.The readmission rate in the CROES URS study was 8.4%at 3 months postoperatively mainly due to fl ank pain and ureteral stent discomfort.In a subgroup analysis reported separately,there was no signi fi cant difference observed for postoperative complications or readmission rates between semirigid and fURS[90].

6.Conclusion

The role of fURS in the management of urolithiasis has expanded greatly during the last 3 decades thanks to the advancing equipment technology and surgical techniques. Increased ureteroscopic skills and experience together with miniaturization of f l exible ureteroscopes has lead to an associated high safety margin for fURS.fURS is expected to play a more important role in the management of urolithiasis in the near future.

Conf l icts of interest

The authors declare no conf l ict of interest.

[1]Marshall VF.Fiber optics in urology.J Urol 1964;91:110e4.

[2]Bagley DH.Active versus passive def l ection in f l exible ureteroscopy.J Endourol 1987;1:15e8.

[3]Grasso M,Bagley D.A 7.5/8.2 F actively def l ectable,f l exible ureteroscope:a new device for both diagnostic and therapeutic upper urinary tract endoscopy.Urology 1994;43: 435e41.

[5]Ankem MK,Lowry PS,Slovick RW,Munoz Del Rio A,Nakada SY. Clinical utility of dual active def l ection f l exible ureteroscope duringuppertractureteropyeloscopy.Urology2004;64: 430e4.

[6]Traxer O,Dubosq F,Jamali K,Gattegno B,Thibault P.Newgeneration f l exible ureterorenoscopes are more durable than previous ones.Urology 2006;68:276e9.

[7]Bach C,Nesar S,Kumar P,Goyal A,Kachrilas S,Papatsoris A, et al.The new digital f l exible ureteroscopes:‘size doesmatter’e increased ureteric access sheath use!Urol Int 2012; 89:408e11.

[8]Traxer O,Thomas A.Prospective evaluation and classif i cation of ureteral wall injuries resulting from insertion of a ureteral access sheath during retrograde intrarenal surgery.J Urol 2013; 189:580e4.

[9]Alexander B,Fishman AI,Grasso M.Ureteroscopy and laser lithotripsy:technologic advancements.World J Urol 2014;33: 247e56.

[10]Yinghao S,Yang B,Gao X.The management of renal caliceal calculi with a newly designed ureteroscope:a rigid ureteroscope with a def l ectable tip.J Endourol 2010;24:23e6.

[11]Desai MM,Aron M,Gill IS,Pascal-Haber G,Ukimura O, Kaouk JH,et al.Flexible robotic retrograde renoscopy: description of novel robotic device and preliminary laboratory experience.Urology 2008;72:42e6.

[12]Desai MM,Grover R,Aron M,Ganpule A,Joshi SS,Desai MR, et al.Robotic f l exible ureteroscopy for renal calculi:initial clinical experience.J Urol 2011;186:563e8.

[13]Saglam R,Muslumanoglu AY,Tokatli Z,C?as?kurlu T,Sarica K, Tas?c?i AI,et al.A new robot for f l exible ureteroscopy:development and early clinical results(IDEAL stage 1-2b).Eur Urol 2014;66:1092e100.

[14]Tu¨rk C,Knoll T,Petrik A,Sarica K,Skolarikos A,Straub M, et al.EAU guidelines on urolithiasis.2013.

[15]SoferM,WattersonJD,WollinTA,NottL,RazviH, Denstedt JD.Holmium:YAG laser lithotripsy for upper urinary tract calculi in 598 patients.J Urol 2002;167:31e4.

[16]Grasso M,Ficazzola M.Retrograde ureteropyeloscopy for lower pole caliceal calculi.J Urol 1999;162:1904e8.

[17]Bas O,Bakirtas H,Sener NC,Ozturk U,Tuygun C,Goktug HNG, et al.Comparison of shock wave lithotripsy,f l exible ureterorenoscopy and percutaneous nephrolithotripsy on moderate size renal pelvis stones.Urolithiasis 2014;42:115e20.

[18]Chung BI,Aron M,Hegarty NJ,Desai MM.Ureteroscopic versus percutaneous treatment for medium-size(1e2-cm)renal calculi.J Endourol 2008;22:343e6.

[19]Ferroud V,Lapouge O,Dousseau A,Rakototiana A,Robert G, Ballanger P.Flexible ureteroscopy and mini percutaneous nephrolithotomy in the treatment of renal lithiasis less or equal to 2 cm.Prog Urol 2011;21:79e84.

[20]Sabnis RB,Jagtap J,Mishra S,Desai M.Treating renal calculi 1e2 cm in diameter with minipercutaneous or retrograde intrarenal surgery:a prospective comparative study.BJU Int 2012;110:E346e9.

[21]Lingeman JE,Folmer M.AUA guidelines on the management of staghorn calculi.AUA Clin Guidel 2005.

[22]Aso Y,Ohta N,Nakano M,Ohtawara Y,Tajima A,Kawabe K. Treatment of staghorn calculi by f i beroptic transurethral nephrolithotripsy.J Urol 1990;144:17e9.

[23]Mugiya S,Suzuki K,Ushiyama T,Fujita K.Combined treatment of staghorn calculi by f i beroptic transurethral nephrolithotripsy and extracorporeal shock wave lithotripsy.Int J Urol 1998;5:129e33.

[24]Grasso M,Conlin M,Bagley D.Retrograde ureteropyeloscopic treatment of 2 cm.or greater upper urinary tract and minor staghorn calculi.J Urol 1998;160:346e51.

[25]Aboumarzouk OM,Monga M,Kata SG,Traxer O,Somani BK. Flexible ureteroscopy and laser lithotripsy for stones>2 cm: a systematic review and meta-analysis.J Endourol 2012;26: 1257e63.

[26]Takazawa R,Kitayama S,Tsujii T.Successful outcome of fl exible ureteroscopy with holmium laser lithotripsy for renal stones 2 cm or greater.Int J Urol 2012;19:264e7.

[27]MiernikA,SchoenthalerM,WilhelmK,WetterauerU, Zyczkowski M,Paradysz A,et al.Combined semirigid and fl exible ureterorenoscopy via a large ureteral access sheath for kidney stones>2 cm:a bicentric prospective assessment. World J Urol 2014;32:697e702.

[28]Akman T,Binbay M,Ozgor F,Ugurlu M,Tekinarslan E,Kezer C, et al.Comparison of percutaneous nephrolithotomy and retrograde f l exible nephrolithotripsy for the management of 2e4 cm stones:a matched-pair analysis.BJU Int 2012;109: 1384e9.

[29]Zeng G,Zhu W,Li J,Zhao Z,Zeng T,Liu C,et al.The comparison of minimally invasive percutaneous nephrolithotomy and retrograde intrarenal surgery for stones larger than 2 cm in patients with a solitary kidney:a matched-pair analysis. World J Urol 2015;33:1159e64.

[30]Breda A,Angerri O.Retrograde intrarenal surgery for kidney stones larger than 2.5 cm.Curr Opin Urol 2014;24:179e83.

[31]Marguet CG,Springhart WP,Tan YH,Patel A,Undre S, Albala DM,et al.Simultaneous combined use of f l exible ureteroscopy and percutaneous nephrolithotomy to reduce the number of access tracts in the management of complex renal calculi.BJU Int 2005;96:1097e100.

[32]Hamamoto S,Yasui T,Okada A,Taguchi K,Kawai N,Ando R, et al.Endoscopic combined intrarenal surgery for large calculi:simultaneous use of f l exible ureteroscopy and minipercutaneous nephrolithotomy overcomes the disadvantageous ofpercutaneousnephrolithotomymonotherapy.J Endourol 2014;28:28e33.

[33]Zeng G,Zhao Z,Wu W,Zhong WEN.Combination of debulking single-tractpercutaneousnephrolithotomyfollowedby retrograde intrarenal surgery for staghorn stones in solitary kidneys.Scand J Urol 2014;48:295e300.

[34]Hamamoto S,Yasui T,Okada A,Koiwa S,Taguchi K,Itoh Y, et al.Eff i cacy of endoscopic combined intrarenal surgery in the prone split-leg position for staghorn calculi.J Endourol 2015;29:19e24.

[35]Elbahnasy AM,Shalhav AL,Hoenig DM,Elashry OM,Smith DS, Mcdougall EM,et al.Lower caliceal stone clearance after shock wave lithotripsy or ureteroscopy:the impact of lower pole radiographic anatomy.J Urol 1998;159:676e82.

[36]Geavlete P,Multescu R,Geavlete B.Inf l uence of pyelocaliceal anatomy on the success of f l exible ureteroscopic approach.J Endourol 2008;22:2235e9.

[37]Resorlu B,Oguz U,Resorlu EB,Oztuna D,Unsal A.The impact of pelvicaliceal anatomy on the success of retrograde intrarenal surgery in patients with lower pole renal stones.Urology 2012;79:61e6.

[38]Jessen JP,Honeck P,Knoll T,Wendt-Nordahl G.Flexible ureterorenoscopy for lower pole stones:inf l uence of the collecting system’s anatomy.J Endourol 2014;28:146e51.

[39]Traxer O.Flexible ureterorenoscopic management of lowerpole stone:does the scope make the difference?J Endourol 2008;22:1847e50.

[40]Kourambas J,Delvecchio F,Munver R,Preminger GM.Nitinol stone retrieval-assisted ureteroscopic management of lower pole renal calculi.J Urol 2012;4295:935e9.

[41]Schuster TG,Hollenbeck BK,Faerber GJ,Wolf JS.Ureteroscopic treatment of lower pole calculi:comparison of lithotripsy in situ and after displacement.J Urol 2002;168:43e5.

[42]Perlmutter AE,Talug C,Tarry WF,Zaslau S,Mohseni H, Kandzari SJ.Impact of stone location on success rates of endoscopic lithotripsy for nephrolithiasis.Urology 2008;71: 214e7.

[43]Martin F,Hoarau N,Lebdai S,Pichon T,Chautard D,Culty T, et al.Impact of lower pole calculi in patients undergoing retrograde intrarenal surgery.J Endourol 2014;28:141e5.

[44]Pearle M,Lingeman J,Leveillee R,Kuo R,Preminger G, Nadler R,et al.Prospective,randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less.J Urol 2005;173:2005e9.

[45]El-Nahas AR,Ibrahim HM,Youssef RF,Sheir KZ.Flexible ureterorenoscopy versus extracorporeal shock wave lithotripsy for treatment of lower pole stones of 10e20 mm.BJU Int 2012;110:898e902.

[46]Kumar A,Vasudeva P,Nanda B,Kumar N,Das MK,Jha SK.A prospective randomized comparison between shock wave lithotripsy and fl exible ureterorenoscopy for lower caliceal stones ?2 cm:a single-center experience.J Endourol 2015;29:575e9.

[47]Bozkurt OF,Resorlu B,Yildiz Y,Can CE,Unsal A.Retrograde intrarenal surgery versus percutaneous nephrolithotomy in the management of lower-pole renal stones with a diameter of 15 to 20 mm.J Endourol 2011;25:1131e5.

[48]Kirac M,Bozkurt O¨F,Tunc L,Guneri C,Unsal A,Biri H.Comparison of retrograde intrarenal surgery and minipercutaneous nephrolithotomy in management of lower-pole renal stones with a diameter of smaller than 15 mm.Urol Res 2013;41: 241e6.

[49]Aboumarzouk OM,Kata SG,Keeley FX,McClinton S,Nabi G. Extracorporeal shock wave lithotripsy(ESWL)versus ureteroscopic management for ureteric calculi(review).Cochrane Database Syst Rev 2012;5:1e44.

[50]Pace KT,Weir MJ,Tariq N,Honey RJ.Low success rate of repeat shock wave lithotripsy for ureteral stones after failed initial treatment.J Urol 2000;164:1905e7.

[51]Hyams ES,Monga M,Pearle MS,Antonelli J a,Semins MJ, Assimos DG,et al.A prospective,multi-institutional study of fl exible ureteroscopy for proximal ureteral stones<2 cm.J Urol 2014;193:165e9.

[52]Kijvikai K,Haleblian GE,Preminger GM,de la Rosette J.Shock wave lithotripsy or ureteroscopy for the management of proximal ureteral calculi:an old discussion revisited.J Urol 2007;178:1157e63.

[53]Ishii H,Aboumarzouk OM,Somani BK.Current status of ureteroscopy for stone disease in pregnancy.Urolithiasis 2014;42: 1e7.

[54]Swartz MA,Lydon-Rochelle MT,Simon D,Wright JL,Porter MP. Admission for nephrolithiasis in pregnancy and risk of adverse birth outcomes.Obstet Gynecol 2007;109:1099e104.

[55]Denstedt JD,Razvi H.Management of urinary calculi during pregnancy.J Urol 1992;148:1072e5.

[56]Laing KA,Lam TBL,McClinton S,Cohen NP,Traxer O, Somani BK.Outcomes of ureteroscopy for stone disease in pregnancy:results from a systematic review of the literature. Urol Int 2012;89:380e6.

[57]Rittenberg MH,Bagley DH.Ureteroscopic diagnosis and treatment of urinary calculi during pregnancy.Urology 1988; 32:427e8.

[58]Watterson JD,Girvan AR,Beiko DT,Nott L,Wollin TA,Razvi H, et al.Ureteroscopy and holmium:YAG lithotripsy:an emerging def i nitive management strategy for symptomatic ureteral calculi in pregnancy.Urology 2002;60:383e7.

[59]Lifshitz D a,Lingeman JE.Ureteroscopy as a f i rst-line intervention for ureteral calculi in pregnancy.J Endourol 2002;16: 19e22.

[60]Semins MJ,Trock BJ,Matlaga BR.The safety of ureteroscopy during pregnancy:a systematic review and meta-analysis.J Urol 2009;181:139e43.

[61]Desai M.Endoscopic management of stones in children.Curr Opin Urol 2005;15:107e12.

[62]Erkurt B,Caskurlu T,Atis G,Gurbuz C,Arikan O,Pelit ES, et al.Treatment of renal stones with f l exible ureteroscopy in preschool age children.Urolithiasis 2014;42:241e5.

[63]Tan AHH,Al-Omar M,Denstedt JD,Razvi H.Ureteroscopy for pediatric urolithiasis:an evolving fi rst-line therapy.Urology 2005;65:153e6.

[64]Kim SS,Kolon TF,Canter D,White M,Casale P.Pediatric fl exible ureteroscopic lithotripsy:the children’s hospital of philadelphia experience.J Urol 2008;180:2616e9.

[65]Ishii H,Grif fi n S,Somani BK.Flexible ureteroscopy and lasertripsy(FURSL)for paediatric renal calculi:results from a systematic review.J Pediatr Urol 2014;10:1020e5.

[66]Unsal A,Resorlu B.Retrograde intrarenal surgery in infants and preschool-age children.J Pediatr Surg 2011;46:2195e9.

[67]Mokhless IA,Abdeldaeim HM,Saad A,Zahran AR.Retrograde intrarenal surgery monotherapy versus shock wave lithotripsy for stones 10 to 20 mm in preschool children:a prospective, randomized study.J Urol 2014;191:1496e500.

[68]Resorlu B,Unsal A,Tepeler A,Atis G,Tokatli Z,Oztuna D, et al.Comparison of retrograde intrarenal surgery and minipercutaneous nephrolithotomy in children with moderatesize kidney stones:results of multi-institutional analysis. Urology 2012;80:519e23.

[69]Ganpule AP,Desai MR.Urolithiasis in kidneys with abnormal lie,rotation or form.Curr Opin Urol 2011;21:145e53.

[70]Atis G,Resorlu B,Gurbuz C,Arikan O,Ozyuvali E,Unsal A, et al.Retrograde intrarenal surgery in patients with horseshoe kidneys.Urol Res 2013;41:79e83.

[71]Weizer AZ,Springhart WP,Ekeruo WO,Matlaga BR,Tan YH, Assimos DG,et al.Ureteroscopic management of renal calculi in anomalous kidneys.Urology 2005;65:265e9.

[72]Molimard B,Al-Qahtani S,Lakmichi A,Sejiny M,Gil-Diez De Medina S,Carpentier X,et al.Flexible ureterorenoscopy with holmium laser in horseshoe kidneys.Urology 2010;76:1334e7.

[73]Bozkurt OF,Tepeler A,Sninsky B,Ozyuvali E,Atis G, Daggulli M,et al.Flexible ureterorenoscopy for the treatment of kidney stone within pelvic ectopic kidney.Urology 2014;84: 1285e9.

[74]Sejiny M,Al-Qahtani S,Elhaous A,Molimard B,Traxer O.Effi cacy of fl exible ureterorenoscopy with holmium laser in the management of stone-bearing caliceal diverticula.J Endourol 2010;24:961e7.

[75]Koopman SG,Fuchs G.Management of stones associated with intrarenal stenosis:infundibular stenosis and caliceal diverticulum.J Endourol 2013;27:1546e50.

[76]Watterson JD,Girvan AR,Cook AJ,Beiko DT,Nott L,Auge BK, et al.Safety and eff i cacy of holmium:YAG laser lithotripsy in patients with bleeding diatheses.J Urol 2002;168:442e5.

[77]Kuo RL,Aslan P,Fitzgerald KB,Preminger GM.Use of ureteroscopy and holmium:YAG laser in patients with bleeding diatheses.Urology 1998;52:609e13.

[78]Turna B,Stein RJ,Smaldone MC,Santos BR,Kefer JC, Jackman SV,et al.Safety and eff i cacy of f l exible ureterorenoscopy and holmium:YAG lithotripsy for intrarenal stones in anticoagulated cases.J Urol 2008;179:1415e9.

[79]Aboumarzouk OM,Somani BK,Monga M.Flexible ureteroscopy and holmium:YAG laser lithotripsy for stone disease in patients with bleeding diathesis:a systematic review of the literature.Int Braz J Urol 2012;38:298e306.

[80]Aboumarzouk OM,Somani B,Monga M.Safety and eff i cacy of ureteroscopic lithotripsy for stone disease in obese patients:a systematic review of the literature.BJU Int 2012;110: E374e80.

[81]Chew BH,Zavaglia B,Paterson RF,Teichman JMH,Lange D, Zappavigna C,et al.A multicenter comparison of the safety and effectiveness of ureteroscopic laser lithotripsy in obese and normal weight patients.J Endourol 2013;27:710e4.

[82]Pompeo A,Molina WR,Juliano C,Sehrt D,Kim FJ.Outcomes of intracorporeal lithotripsy of upper tract stones is not affected by BMI and skin-to-stone distance(SSD)in obese and morbid patients.Int Braz J Urol 2013;39:702e11.

[83]Best SL,Nakada SY.Flexible ureteroscopy is effective for proximal ureteral stones in both obese and nonobese patients: a two-year,single-surgeon experience.Urology 2011;77:36e9.

[84]Caskurlu T,Atis G,Arikan O,Pelit ES,Kilic M,Gurbuz C.The impact of body mass index on the outcomes of retrograde intrarenal stone surgery.Urology 2013;81:517e21.

[85]Delorme G,Huu YN,Lillaz J,Bernardini S,Chabannes E, Guichard G,et al.Ureterorenoscopy with holmium-yttriumaluminum-garnet fragmentation is a safe and eff i cient technique for stone treatment in patients with a body mass index superior to 30 kg/m2.J Endourol 2012;26:239e43.

[86]Sari E,Tepeler A,Yuruk E,Resorlu B,Akman T,Binbay M,et al. Effect of the body mass index on outcomes of f l exible ureterorenoscopy.Urol Res 2013;41:499e504.

[87]Sanguedolce F,Liatsikos E,Verze P,Hruby S,Breda a, Beatty JD,et al.Use of f l exible ureteroscopy in the clinical practice for the treatment of renal stones:results from a large European survey conducted by the EAU young academic urologists-working party on endourology and urolithiasis. Urolithiasis 2014:329e34.

[88]Rajamahanty S,Grasso M.Flexible ureteroscopy update:indications,instrumentation and technical advances.Indian J Urol 2008;24:532e7.

[89]de la Rosette J,Denstedt J,Geavlete P,Keeley F,Matsuda T, Pearle M,et al.The clinical research off i ce of the endourological society ureteroscopy global study:indications,complications,and outcomes in 11,885 patients.J Endourol 2014; 28:131e9.

[90]Perez Castro E,Osther PJS,Jinga V,Razvi H,Stravodimos KG, Parikh K,et al.Differences in ureteroscopic stone treatment and outcomes for distal,mid-,proximal,or multiple ureteral locations:the clinical research off i ce of the endourological society ureteroscopy global study.Eur Urol 2014;66:102e9.

Received 3 June 2015;accepted 9 June 2015 Available online 23 June 2015

*Corresponding author.

E-mail address:john.denstedt@sjhc.london.on.ca(J.D. Denstedt).

Peer review under responsibility of Shanghai Medical Association and SMMU.

http://dx.doi.org/10.1016/j.ajur.2015.06.002

2214-3882/a2015 Editorial Off i ce of Asian Journal of Urology.Production and hosting by Elsevier(Singapore)Pte Ltd.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).