E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5

available at www.sciencedirect.com
journal homepage: www.europeanurology.com/eufocus

Review – Endo-urology

The Evolving Role of Retrograde Intrarenal Surgery in the

Treatment of Urolithiasis

Francesco Sanguedolce a,b,*, Giorgio Bozzini c, Ben Chew d, Panagiotis Kallidonis e,

Jean de la Rosette f
a
Department of Urology, Fundació Puigvert, Autonomous University of Barcelona, Barcelona, Spain; b Department of Urology, King’s College Hospital, King’s
College London, London, UK; c Department of Urology, Mater Domini Humanitas Hospital, Milan, Italy; d Department of Urology, Vancouver General Hospital,
University of British Columbia, Vancouver, BC, Canada; e Department of Urology, Patras University Hospital, University of Patras, Patras, Greece; f Department
of Urology, AMC University Hospital, University of Amsterdam, Amsterdam, the Netherlands

Article info Abstract

Context: Retrograde intrarenal surgery has gained substantial popularity worldwide thanks
[47_TD$IF]Associate Editor: James Catto to continuous improvements in technology and techniques, and is now considered one of
the first-line treatment options for active removal of renal stones.
Objective: To provide a comprehensive synthesis of the main evidences in literature on the
current management of kidney stones by means of retrograde intrarenal surgery (RIRS).
Keywords: Evidence acquisition: A review of literature has been conducted using search string
Renal stones “retrograde intrarenal surgery OR flexible ureteroscop* OR ureterorenoscop*”, without
Urolithiasis any language restriction; PubMed, Embase, and Scopus databases were searched in Novem-
Flexible ureteroscopy ber 2016. Exclusion criteria involved manuscripts dealing with paediatric patients, and RIRS
for proximal ureteric stones and for upper tract urothelial tumours. Fifty-seven papers were
Retrograde intrarenal surgery finally included in the analysis.
Evidence synthesis: Technological progress focuses on the miniaturisation of disposables
and scopes, as well as on the increase of durability and improvement of the quality of image
provided by these instruments. The technique has been in continuous development
following the progress in technology. Currently, the main target of RIRS are renal stones
1–2 cm in size, even though tertiary centres are pushing the boundaries to the treatment of
larger stones. Nomograms predicting surgical outcomes and improving preoperative sur-
gical planning have been developed. RIRS has been shown to be safe and effective in patients
with specific conditions such as bleeding diathesis, anatomical malformation, or pregnancy.
Cost effectiveness of the approach is still a matter of controversy when compared with other
treatment modalities.
Conclusions: RIRS is a well-established procedure under constant evolution with advances
in technique and technology. It has gained worldwide popularity due to its minimal
invasiveness and satisfactory outcomes. Future developments are needed to increase its
cost effectiveness and extend its use to a wider range of indications.
Patient summary: In this collaborative review, we have summarised the best evidence in
literature with respect to current management of renal stones by means of retrograde
intrarenal surgery (RIRS) with flexible ureteroscopy. RIRS has been shown to be a safe and
effective treatment modality in a wide spectrum of clinical scenarios; technology and
technique are continuously evolving to further push boundaries of its indications and efficacy.
© 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Fundació Puigvert, Autonomous University of Barcelona, Spain; C/Cartagena

340-350, Barcelona 08025, Spain. Tel. +34934169700; Fax: +34934169730.
E-mail addresses: fsangue@hotmail.com, francesco.sanguedolce@nhs.net,
fsanguedol@fundacio-puigvert.es (F. Sanguedolce).

http://dx.doi.org/10.1016/j.euf.2017.04.007
2405-4569/© 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5 47

1. Introduction from inception to November 2016. Papers eligibility

The concept of the endoscopic access to the renal collecting
systems for the diagnosis and treatment of upper urinary
tract diseases was firstly introduced by V. Marshall [1] who
first described in 1964 the navigation in the renal pelvis
with a rudimental flexible fibrescope. It has been only in the
last 30 yr that miniaturisation and advances in technology
have allowed a progressive improvement in techniques and
their extensive employment in the clinical practice. Today,
retrograde intrarenal surgery (RIRS) by means of flexible
ureterorenoscopes (fURSs) is considered one of the first-line
treatment options for the active removal of renal stones
[2,3].
In this collaborative review, we aimed to provide a
comprehensive synthesis of the main evidence in literature
regarding the current role of RIRS for the treatment of renal
stones.
2. Evidence acquisition
A review of literature has been conducted using search
string “retrograde intrarenal surgery OR flexible ureteroscop*
OR ureterorenoscop*”, without any language restriction;
[(Fig._1)TD$IG]
PubMed, Embase, and Scopus databases were searched
included systematic reviews, randomised controlled trials
(RCTs), observational/longitudinal comparative studies,
and cohort series; editorial, comments, or letter to the
editors were excluded.
Exclusion criteria involved manuscripts dealing with
paediatric patients as well as the use of RIRS for proximal
ureteric stones and for upper tract urothelial tumours. A
first screen for titles and abstracts of the articles was con-
ducted by the first author (F.S.); the final list of manuscripts
was agreed by senior authors in agreement with the first
author and the supervising senior author (J.d.l.R.). Articles
with the highest level of evidence and/or relevance pro-
vided in each subtopic of interest were included. A flow
chart describing the selection process is shown in Fig. 1.
3. Evidence synthesis
3.1. Technology
During the last 3 decades, significant advances in technol-
ogy improved the efficacy of RIRS with the use of fURSs.
These advances include miniaturisation of the endoscopes
and their improvement in terms of image quality and
durability.

Records idenfied through

database searching (n = 3004)
Idenficaon

(Embase 1187, PubMed 957, Addional records idenfied

Scopus 860) through other sources (n = 6)

Records aer duplicates removed by tles

(n = 606)
Screening

Records screened by abstracts Records excluded with

(n = 421) reasons:
 Upper urothelial
cancer (n = 38)
 Narrave reviews
(n = 18)
Eligibility

 Editorial, comments,
Full-text arcles assessed or leer to the editors
for eligibility (n = 97) (n = 49)
 Other reasons
(n = 219)
Included

Studies included in
qualitave synthesis
(n = 61)

Fig. 1 – PRISMA 2009 flow diagram. PRISMA = Preferred Reporting Items for Systematic Review and Meta-analyses.
48 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5

Manufacturers have reduced the calibre of the latest
generation of fURS. The size of the scopes depends on the
model and its characteristics (eg, fibreoptic vs digital
scopes), while most of the fURSs are equipped with a
standard 3.6 Fr working channel and a 270 deflection
system in both directions [4].
Table 1 summarises the characteristics of currently avail-
able flexible [48_TD$IF]ureteroscopes according to features reported
by manufacturers.
The durability of fURSs remains one of the most impor-
tant issues. A randomised comparative trial evaluated the
lifespan of different ureteroscopes, including Wolf Viper,
Olympus URF-P5, Gyrus-ACMI DUR-8 Elite, and Stryker
FlexVision U-500; the mean device durability ranged from
5.3 to 18 cases before major repairs were needed [5]. Rea-
sons for repair included poor visibility (42%), decrease of
manoeuvrability (25%) and damage of working channel due
to laser misfiring (8%).
Digital scopes have been introduced to improve the
outcomes by providing better visibility, manoeuvrability,
and durability. Nevertheless, a comparative study failed to
prove a difference in stone-free rates (SFRs) (88% vs 86% at
1 mo) between the digital (Olympus URF-V) and the
fibreoptic (Olympus URF-P5) scopes. On the other side,
digital scopes allowed a 20% reduction of the operative
time,which was considered as a surrogate of its better
visibility and manoeuvrability [6]. It should be noted that
no evidence is available for demonstrating the higher dura-
bility of digital scopes compared with the conventional
ones.
Furthermore, disposable scopes have been developed to
overcome some of the limitations of reusable fURS, such as
the ability to keep optimal deflection, manoeuvrability, and
visibility all the time; the lack of need for sterilisation; and
potentially enabling a reduction of costs [7]. However, few
publications are available in literature to support cost effec-
tiveness of these devices; LithoVue, a new single-use digital
flexible ureteroscope is among the latest disposables more
tested in literature. In a European multicentric study, the
device was used in 40 patients and surgeons’ satisfaction
was reported in a Likert-like scale [8]. Even though a small
number of cases and reporting bias affected the power of
the study, “very good” and “good” ratings were mostly
recorded for image quality and manoeuvrability (65% and
30%, and 77.5% and 17.5%, respectively). These results were
consistent both pre- and postoperatively. Deflection sys-
tems were not affected after any of the recorded operation;
however, comparative outcomes or cost-analysis are still
waited.
Robotic technology has recently been introduced in RIRS
with the Avicenna (Elmed Medical Systems, Ankara, Turkey)
robotic system. It consists of a console where the surgeon
manoeuvres remotely the robotic arm where the flexible
scope is fixed; a memory function of the system allows
automatic relocation of the scope to a previously identified
calyx for targeting and lasering the stone. The preliminary
results showed that it provides a suitable and safe platform
for robotic RIRS with significant improvement of ergonom-
ics [9].Nonetheless, the main concern is cost effectiveness,
which may hinder its acceptance in the common practice.
Several ureteral access sheath (UAS) models have
recently been introduced in the market with different cali-
bres and material to reduce insertion trauma. The use of
UASs is associated with advantages such as facilitating
multiple and quick entries and exits, less traumatism to
the scopes, and reduction of intrarenal pressures. An exper-
imental study addressed the latter issue: five UASs have
been tested with eight fURS on an artificial kidney model to
measure intrarenal pressures and irrigation flow of different
configurations of UAS and fURS [10]. The measurements
varied depending on the size of scopes fitting in the relevant
UASs. The main message of this study was that an appro-
priate UAS should be selected before surgery according to
the scope size and surgical plan. The authors also suggested
that the 10/12Fr UAS may be considered the ideal size fitting
for most of the fURSs, guaranteeing an optimal balance
between intrarenal pressure and irrigational flow.
3.2. Technique
RIRS is a multistep procedure with many variants proposed
in the literature. A common point of debate is the utility of
prestenting de ureter: the largest experience in this regard
has been published by Jessen et al [11] with 253 patients

Table 1 – Characteristics of reusable and disposable flexible ureteroscopes.

Scope Use Optical system Tip calibre Shaft calibre Deflection (up/down) Working channel calibre

Olympus URF-P5 Reusable Fibreoptic 5.3 8.4 180/275 3.6

Olympus URF-P6 Reusable Fibreoptic 4.9 7.95 275/275 3.6
Olympus URF-V Reusable Digital 8.3 9.9 180/275 3.6
Olympus URF-V2 Reusable Digital 8.5 8.4 275/275 3.6
Storz Flex-X2 Reusable Fibreoptic 7.5 7.5 270/270 3.6
Storx Flex-X2S Reusable Fibreoptic 7.5 7.5 270/270 3.6
Storz Flex-XC Reusable Digital 8.5 8.4 270/270 3.6
Wolf Viper Reusable Fibreoptic 6 8.8 270/270 3.6
Wolf Boa Reusable Digital 6.6 8.9 270/270 3.6
Wolf Cobra Reusable Digital 5.2 9.9 270/270 2.4 + 3.6
Lumenis—Polyscope Disposable Fibreoptic 8 8 250/0 3.6
Maxiflex—Semi-Flex Disposable Fibreoptic 8.3 8.3 270/270 3.4
Boston Scientific—Lithovue Disposable Digital 7.5 9.5 280/280 3.6
Zhuhai Pusen Medical Technology—Uscope Disposable Digital 6.5 9 270/270 3.6
 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5
with renal stones only, retrospectively reviewed comparing
surgical outcomes in subgroups of patients with and with-
out a pre-RIRS stent. They found that prestented patients
had a benefit in terms of a higher SFR and a lower compli-
cation rate (p: 0.001 and p: 0.021, respectively), but no
advantages were noticed for what concerns the operative
time; the authors attributed these outcomes to the passive
dilatation of the ureter, which may (1) ease UAS insertion,
(2) contribute in keeping the intrarenal pressure low, and
(3) facilitate navigation with fURS in the collecting system.
On the other side, prestented patients may experience
stent-related side effects, which usually are not reported
in retrospective series.
The Clinical Research Office of the Endourological Soci-
ety (CROES) analysed data from 2239 RIRS comparing the
surgical outcomes of subgroups of patients who had a UAS
inserted with those who were treated without any UAS
insertion. Although no difference of SFR was shown, the
use of a UAS was associated with fewer postoperative
infective complications. The latter phenomenon could be
attributed to the lower intrarenal pressures without an
increase of ureteric injuries or bleeding [12].
A common strategy to reduce damages on working chan-
nels and deflection systems is the relocation of a lower pole
stone to a more suitable position within the collecting system
by means of a tipless nitinol basket. A comparative study
showed that the replacement technique had higher SFRs for
patients with lower pole stones of 1–2 cm than the fragmen-
tation of the stones in situ (100% vs 29%, p = 0.0005) [13].
A retrospective study challenged the need to retrieve
fragments after renal stone fragmentation during RIRS. A
total of 172 patients whose fragments were lasered and
basketed were compared with 76 patients who had their
stones lasered only. No significant differences were identified
in terms of SFRs (89.0% vs 86.8%), operative time (82.5 vs
82.1 min), and overall complication rates (9.9% vs 11.8%) [14].
Two large international surveys investigated practi-
tioners’ preferences when performing RIRS. In both studies,
most of the urologists expressed their preference in using
UAS (58.3–70.7% of respondents), relocating a lower pole
stone in a less dependent calyx before fragmentation (45.9–
55.8%), and retrieving only the larger fragments (37.4–47.2)
[15,16].
Another technical aspect is the placement of a double-J
stent after RIRS. Although the insertion of a stent is a proce-
dure that is routinely performed, its cost effectiveness has not
yet been demonstrated [17]. On the other side, a matched-pair
study comparing patients with postoperative stent versus
those without after RIRS performed with the aid of a UAS
showed a potential benefit of stenting in terms of better
control of postoperative pain [18]. However, authors sug-
gested that stenting could be spared in patients who were
stented preoperatively because of the less traumatic insertion
of UAS, as well as in case of uneventful procedures.
3.3. Surgical outcomes
The efficacy of RIRS in the setting of renal stone patients
depends on stone (composition/hardness, number, and
49
size), anatomical site (eg, lower pole, calyceal diverticulum,
length of infundibulum, pelvic-infundibulum angle), and
surgeon (volume/experience) characteristics. Moreover,
reports in the literature on SFRs are biased by nonstandar-
dised definition of clinically residual fragments (RFs), meth-
odology (intraoperative endoscopy, intraoperative fluoros-
copy, noncontrasted computed tomography (CT), x-ray of
kidneys, ureters, and bladder [KUB], US KUB), and timing of
assessment.
Regardless these limitations, many papers have been
published testing the safety and efficacy of RIRS for the
treatment of renal stones during the last years. The Euro-
pean Association of Urology guidelines on urolithiasis
recommends the use of RIRS as a first-line treatment
option for renal stones <2 cm, alternative to shock wave
lithotripsy (SWL) or percutaneous nephrolithotomy (PCNL)
[2]. Similar recommendations are provided by the com-
bined guidelines on surgical management of stones from
the American Urological Association and the Endourologi-
cal Society, with just the exception of lower pole stones of
1–2 cm in size where PCNL is preferred as a first-line
treatment option [3].
A CROES study analysed data from 1210 patients col-
lected prospectively worldwide from 2010 to 2012; authors
found high SFRs for stones of <10 and 15 mm in size (90%
and 80%, respectively) obtained after a single session of
RIRS. These results were associated with a low complication
rate. They concluded that single renal stones up to 15 mm
are effectively treated with RIRS in one session, while better
outcomes may depend on surgeon’s volume and expertise
[19].
In a meta-analysis of 10 studies comparing RIRS with
PCNL, De et al [20] reported higher SFRs for PCNL patients
(weighted mean difference [WMD]: 2.19; 95% confidence
interval [CI] 1.53–3.13; p < 0.00001), even though RIRS
showed lower complication rates (odds ratio [OR]: 1.61;
95% CI 1.11–2.35; p < 0.01), blood loss (WMD: 0.87; 95% CI
0.51–1.22; p < 0.00001), and hospital stay (WMD: 1.28; 95%
CI 0.79–1.77; p < 0.0001; Table 2). Similar outcomes were
observed in the subgroup analysis when comparing RIRS
with minimally invasive PCNL [21]. However, results from
the meta-analysis were limited by the significant heteroge-
neity of included studies and by the different modalities
used by authors in reporting outcomes, including different
definitions of SFR and type of imaging.
Other systematic reviews involving RIRS focused on a
specific range of stone size and location. In a meta-analysis
of seven RCTs comparing PCNL, RIRS, and SWL for lower pole
stones <20 mm, Donaldson et al [22] reported overall SFRs
of 96.3%, 91.7%, and 54.5%, respectively. Five of the selected
studies compared directly RIRS with SWL. In this subgroup
analysis, RIRS was confirmed to be more effective (SFR:
89.5% vs 70.5%), especially for stones 10–20 mm (relative
risk [RR]: 1.5; 95% CI 1.20–1.87; p: 0.0003), while complica-
tion rates were comparable. The meta-analysis of studies
comparing PCNL with RIRS could not be performed as only
one RCT compared the two techniques. In the latter investi-
gation, no statistical differences in SFRs were found
(Table 2).
50 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5

Table 2 – Summary of surgical outcomes from comparative systematic reviews and meta-analysis with RIRS versus SWL and/or PCNL.

Authors Year of Size of Site of RCT/ No. of SFR (95% CI) Complication (95% CI)
publication renal renal non-RCT pts
stones stones included

De et al [20] 2015 Any size Any site 2/8 1181 PCNL/RIRS RIRS/PCNL
WMD: 2.19 (1.53–3.13)* OR: 1.61 (1.11–2.35)*
Donaldson 2015 2 cm Lower pole 7/0 691 RIRS/SWL RIRS/SWL
et al [22]
RR: 1.31 (1.08–1.59)* RR (range): 0.65–1.67
PCNL/RIRS PCNL/RIRS
RR: 1.44 (0.73–2.87)# NA
Zheng et al 2015 1–2 cm Any site 3/4 983 SWL/RIRS SWL/RIRS (Clavien–Dindo)
[23]
RR: 0.86 (0.77–0.95)* Grade 1 RR: 1.06 (0.67–1.69)#
Grade 2 RR: 0.75 (0.29–1.91)#
Grade 3 RR: 0.86 (0.26–2.86)#
Zheng et al 2014 >2 cm Any site 2/6 590 RIRS/PCNL RIRS/PCNL
[25]
RR: 0.95 (0.88–1.02)# Fever RR: 0.95(0.54–1.67)#
Bleeding RR: 0.20 (0.06–0.68)*

CI = confidence interval; NA = not applicable; OR = odds ratio; PCNL = percutaneous nephrolithotomy; pts = patients; RCT = randomised controlled trial;
RIRS = retrograde intrarenal surgery; RR = relative risk; SWL = shock wave lithotripsy; WMD = weighted mean difference.
*
Statistically significant.
#
Not statistically significant.

Another systematic review and meta-analysis has been
conducted to compare the efficacy of RIRS and SWL for renal
stones of 1–2 cm [23]. Seven papers were selected for the
quantitative analysis: SWL showed inferiority to RIRS in
terms of a lower SFR (RR: 0.86; 95% CI 0.77–0.95, p: 0.005)
and a higher retreatment rate (RR: 8.12; 95% CI 4.77–13.83,
p < 0.0001); more interestingly, they did not find any dif-
ference of complication rates, which traditionally were
thought to favour SWL (Table 2). However, the pooled out-
comes were once again limited by the heterogeneity of the
selected studies, small sample of patients, and inconsis-
tency in defining SFR and reporting the outcomes.
In the last years, growth of expertise and refinement of
technology have prompted more and more surgeons to
push indication for RIRS for larger renal stones, which are
traditionally managed by PCNL. Aboumarzouk et al [24]
systematically reviewed the literature to assess effective-
ness and safety of RIRS for renal stones >2 cm; they found a
combined SFR of 93.7% (77–97.5%) with 1.6 sessions in
average for treating renal stones of 2.5 cm in mean size.
Complication rates were 10.1%, equally distributed between
minor and major complications, with the latter accounting
mainly for postoperative steinstrasse, subcapsular haema-
toma, and obstructive pyelonephritis. When stratifying for
stones 2–3 and >3 cm, the SFR was 95.7% versus 84.6% (OR:
4.03; 95% CI 1.38–11.72, p: 0.01). Moreover, patients with 2–
3 cm stones underwent fewer procedures than those with
stones >3 cm (mean 1.46 vs 1.85, p: 0.0001; 95% CI: 0.42 to
0.36) and experienced less minor and major complications
(14.3% vs 15.4%, and 0% vs 11.5%), respectively.
In the same subset of patients with >2 cm renal stones,
Zheng et al [25] conducted a meta-analysis of studies
comparing RIRS with PCNL. The pooled results showed no
difference in terms of SFRs (RR: 0.95; 95% CI 0.88–1.02, p:
0.11) but highlighted significantly lower bleeding (RR: 0.20;
95% CI 0.06–0.68, p: 0.01) and shorter hospital stay (WMD:
2.10; 95% CI 3.08 to 1.11, p: 0.01) in favour of RIRS
(Table 2). Accordingly, the authors concluded that RIRS
could be considered an alternative to PCNL also in the
setting of large renal stones in selected cases and in tertiary
high-volume centres.
A large cohort study of 1571 RIRSs focused only on
complications and found that the three most significant
factors associated with undesired events were stone size,
number of stones, and presence of a congenital renal abnor-
mality [26]. On the other hand, RIRS was not associated with
a higher risk of complications in the case of unfavourable
clinical conditions such as old age, high body mass index,
higher American Society of Anesthesiologists score, pres-
ence of a bleeding diathesis, or having a solitary kidney.
In another cohort of 647 patients from Turkey, hospital
readmission occurred in 12.7% of patients and 4.8% were
rehospitalised for subsequent treatment [27]. Predictive
factors for hospital readmission included the presence of
RF, postoperative complication, or prolonged hospitalisa-
tion postoperatively. Interestingly, readmission rate was not
decreased by postoperative stenting; considering that
almost 80% of patients in this cohort were stented postop-
eratively, these data may further suggest that routine post-
operative stenting is not beneficial to all patients and should
be performed in selected cases.
Traxer and Thomas [28] examined 167 cases where the
UAS was used and determined that 46.5% of cases displayed
a ureteral wall injury. Low-grade injuries (grade 0 or 1)
comprised the vast majority of these injuries (86.6%) with
only 10.1% comprising grade 2 (mucosa and smooth muscle)
and 3.3% with grade 3 injuries (perforation). No ureteral
avulsions (grade 4) were observed. Prestenting reduced the
risk of ureteral injury from UAS by seven-fold: accordingly,
the authors recommended the use of UAS in those patients
who have a higher stone burden requiring more intraur-
eteral passages to retrieve fragments and in those patients
 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5
who are prestented. It should be noted that 12-14Fr UASs
were used in the study, which is in contrast to the 10-12Fr
UASs that are now mostly used; this factor may explain the
high rate of ureteric injuries [16].
Delvecchio et al [29] reported a 1.4% rate of ureteral
stricture in 150 patients who underwent ureteroscopy with
the use of a UAS. They found only one patient in their series
developing a stricture at the ureteropelvic junction after
multiple ureteroscopies for infectious struvite stones.
In a multicentre retrospective study, infectious compli-
cations occurred in <8% of patients following ureteroscopy.
These complications included fever (4.4%), systemic inflam-
matory response syndrome (1.7%), and urosepsis (0.7%)
[30]. Multivariate analysis did not identify any preoperative
risk factors that were predictive for postoperative infection.
Nevertheless, the univariate analysis showed the presence
of diabetes, hyperlipidemia, coronary artery disease, anti-
coagulant therapy, past surgery for stones, and RFs to be
significant risk factors for infectious events.
The routine administration of postoperative antibiotic
prophylaxis is not recommended as there are no robust data
proving a risk reduction for postoperative infection [2].
Fatalities during or after RIRS are rare: a recent survey
among 11 expert endourologists reported six deaths with
sepsis being the main cause (n = 4), and anaesthetic and
haemorrhagic complications being the others [31]. Notably,
a history of urinary tract infection was present in three
patients, which may have contributed to the development
of the fatal complications: this report should be used as a
further warning for practitioners to adopt all the preopera-
tive clinical measures to prevent septic complications espe-
cially in high-risk patients.
3.4. Nomograms and predictive factors
Predictive scoring systems and nomograms take preopera-
tive factors into consideration to help urologists in deter-
mining the chance of achieving stone-free status, and to
accurately counsel patients regarding the procedure. The
Resorlu–Unsal stone score (RUSS) consists of four parame-
ters with a score of 0 or 1 for each parameter [32]. The
scoring system has been validated by separating patients
into four different groups (0–3): lower scores portended a
higher SFR, while higher scores indicated more complex
stones and a lower SFR. Some of these factors include stone
size, number, and location, including lower calyceal stones,
stone size >20 mm, more than one stone, or abnormal
anatomy. The SFRs (85%, 71%, 50%, and 25%) correlated well
(from least complex to more complex stones) with RUSS
scores of 0, 1, 2, and 3, respectively.
In comparison, the Seoul National University Renal
Stone Complexity scoring system (S-ReSC-R) separated
patients into more groups [33,34]. The scoring system
ranges from 1 to 12, with the higher number containing
more complex stones in terms of number, size, and loca-
tion. Those with low or intermediate S-ReSC-R scores (1–2
and 3–4) had higher SFRs (70.2% and 86.7%) than those
with high scores (5–12; 48.6%, p < 0.001). The authors
compared the S-ReSC-R score with the RUSS score, with
51
the former predicting the SFR with a higher rate of accu-
racy. However, another study compared the same two
scoring systems in a retrospective fashion in 339 patients
and found that the RUSS score was more accurate in
predicting the SFR than the S-ReSC-R score [35]. Thus, it
is currently impossible to suggest which of the above SFR
predicting scoring systems is most accurate.
A study to develop and internally validate a predictive
nomogram for all stones was performed in 310 patients
with CT follow-up [36]. Five factors were found to be
predictive of stone-free status: stone volume, stone number,
hydronephrosis, stone location in the lower calyx, and stone
density (Hounsfield units on CT). In addition, the authors
also determined that surgeon experience was predictive of
the stone-free status. In surgeons who had >50 ureterosco-
pies in their experience, patients had an OR of 2.07 (95% CI
1.02–4.19, p = 0.043) of being stone free compared with
surgeons who had performed <50 cases. Another study
evaluated five different institutions and categorised sur-
geons as early-career surgeons (<400 RIRS procedures) to
more senior surgeons (>400 procedures) [37]. The overall
SFR was not significantly different between the two groups
(70% vs 78%), while the complication rate was significantly
lower in the more experienced group (OR: 0.36; 95% CI
0.20–0.67).
Other studies have looked at specific factors that can
affect the SFR for RIRS for lower calyceal stones. In a study of
67 patients treated with RIRS for lower pole stones, multi-
variate analysis found an infundibulopelvic angle of <30 ,
short infundibular length, large infundibular width, and a
low calyceal pelvic height as factors associated with a lower
SFR [38].
The EDGE Research Consortium published on the fate of
RFs after URS showing that although 56% of patients with
RFs had no problems after the procedure, 29% of patients
with RFs required a secondary intervention and another 15%
experienced complications from their RFs even though
these latter group did not require intervention [39]. More-
over, fragments >4 mm were more likely to grow over time
and were more commonly associated with complications
compared with those that were 4 mm or smaller.
3.5. Combined approaches with RIRS
RIRS has been proposed in association with other techni-
ques to maximise efficacy and reduce morbidity in specific
settings of stone patients.
The most common combined treatment involves RIRS
and PCNL. The first to propose such an approach were
Grasso et al [40] who reported their cohort of 45 patients
treated by combining prone PCNL with fURS with either a
split-leg or a flank-roll position. Further development of
technique was proposed by Ibarluzea et al [41] who per-
formed PCNL in the supine position with the Galdakao-
modified supine Valdivia position. The so-called endoscopic
combined intrarenal surgery (ECIRS) provided an easier
retrograde approach with fURS, with subsequent high ver-
satility of collecting system manipulation and reduced
number of punctures needed, while preserving the alleged
52 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5
anaesthesiological advantages by keeping the patient in a
supine position [42].
The combination of mini-PCNL and RIRS (mini-ECIRS)
for large renal stones has also been proposed, which
has shown a significantly higher SFR (81.7% vs 38.9% vs
45.1%; p < 0.001), and shorter operative (120.5 vs 181.9 vs
134.1 min; p < 0.001) and hospital stay (7 vs 8.3 vs 12.9 d;
p = 0.033) time compared with mini- and conventional
PCNL [43].
ECIRS was evaluated in the management of special con-
ditions, such as in children and the elderly, patients at high
risk, obese patients, as well as cases with skeletal and renal
anomalies. Patients with stones in transplanted kidneys
were also treated with combined RIRS and PCNL
[44,45]. The approach provided promising results in the
managements of the above cases.
RIRS has also been combined with SWL for the manage-
ment of large stones in patients refusing or unsuitable for
PCNL [46]. Only 14% of the patients were stone free after the
first combined session, while 84.6% of the cases were suc-
cessful after secondary sessions. Another interesting con-
cept was the combination of RIRS and laparoscopic ureter-
olithotomy in patients with large renal stones [47]. The fURS
was percutaneously inserted through a trocar in order to
remove concomitant renal stones. The access to the collect-
ing system was possible through an incision of the ureter,
and renal stones were extracted with an endoscopic basket.
3.6. RIRS in the management of special conditions
Special medical conditions such as bleeding diathesis, obe-
sity, skeletal anomalies, or even pregnancy may complicate
or even contraindicate indications for active treatments of
renal stones [48–50]. The establishment of RIRS as an
approach for the management of renal stones has also
provided a valuable tool in the setting of the aforemen-
tioned cases.
A systematic review of the literature revealed that RIRS
could be performed in patients receiving warfarin, low or
high doses of aspirin, as well as clopidogrel [48]. Cases with
thrombocytopenia and liver dysfunction were also treated
successfully. The efficacy of RIRS in this setting of patients
was high (SFR 81.1–96%), and the incidence of bleeding
complications remained low, with only 4% of patients
experiencing minor bleeding.
Obese patients are prone to experience anaesthesiologi-
cal and surgical complications. A systematic review showed
that these patients with stones up to 2 cm were effectively
managed with RIRS [51]. A range of SFRs between 33% and
97% was reported in several studies, which included both
ureteric and renal stones. Stones >2 cm were also included
in these investigations. The SFR was higher in the case of
ureteric stones and when the stones were <2 cm. Lower
figures of this SFR range (ie, 33%) was due to the results from
one of the included studies with large stones up to 7.2 cm
(mean 3.8 cm) managed with RIRS. Low complication rates
were also reported in the available experience.
Urolithiasis during pregnancy, when conservative man-
agement fails or is not indicated, has been managed with
ureteroscopy for more than 2 decades, considering that SWL
and PCNL are both contraindicated in this setting of patients
[2]. The majority of the available studies include a small
number of RIRS cases; nevertheless, ureteroscopy was
related with minimal complications, while obstetric com-
plications did not result in any foetal or maternal deaths
[49].
Anatomical issues associated with the skeleton and the
kidney could undermine or complicate the efficacy of SWL
and PCNL for the treatment of urinary calculi. Nevertheless,
patients with spinal deformities were successfully treated
with RIRS with high SFRs (66.6–85.7%), and complications
were encountered with an incidence of up to 22%
[50,52]. Lithiasis in anomalous kidneys and horseshoe kid-
neys has successfully been treated with RIRS. The technique
had a relatively high SFR in comparison with SWL and PCNL
without having the same complications [53]. Stones in
calyceal diverticula may cause symptoms and their man-
agement is complex. SWL has low success rates; although
PCNL has been regarded as the golden standard, the pro-
cedure has significant technical challenges, especially in the
cases of anterior diverticula, and is more invasive than the
other approaches. In a comparative retrospective study,
Bas et al [54] reported a similar SFR of RIRS to PCNL,
with a higher number of major complications recorded
during PCNL. It is worth to notice that diverticular stones
treated with PCNL were larger in mean size (154  77 vs
211  97 mm2[46_TD$IF]; p = 0.023). SFRs up to 93.1% have been
reported for patients with solitary kidneys with renal stones
2 cm after secondary sessions [55]. The main concern for
the latter cases was the possibility of compromising the
renal function, especially as a result of eventual ureteric
stricture caused by manipulation of ureter during RIRS;
nonetheless, the authors did not reported any ureteric
stricture. The complication rates involved only Clavien
grade I events. No significant change of serum creatinine
was noticed in 1-yr follow-up [55]. Stones in transplanted
kidneys have also been successfully treated with RIRS. High
SFRs without deterioration of the renal function of the
kidney was noted. A minor increase in creatinine could take
place within the first postoperative days and eventually
subsides during the follow-up period [56].
3.7. Cost
The analysis of cost for RIRS includes a number of factors
such as the cost of scopes and their maintenance (including
needs of repair), local reimbursement policies, cost of dis-
posables, training of surgeons, staff expertise, and environ-
mental costs (theatre usage, length of hospital admission,
postoperative drugs, day off work, eventual removal of
double-J stent).
Collins et al [57] first highlighted the impact of costs for
disposables, which, in their experience, overcome those for
the purchase of the fURS and of the two repairs needed
within the span of the 100 cases performed during the
observed time.
In a head-to-head cost analysis comparing SWL with
RIRS for lower pole stones, Koo et al [58] found that overall
 E U R O P E A N U R O L O G Y F O C U S 3 ( 2 0 17 ) 4 6 – 5 5
costs for the hospital were significantly lower for SWL.
Nevertheless, these results could not be generalised since
some of the outcomes were not consistent with the current
data available in the literature, such as a high number of
auxiliary procedures needed for RIRS and a mean hospital
stay of nearly 3 d for a procedure that is nowadays offered
even as day surgery.
Cost analysis was also carried out in a comparative series
between PCNL and RIRS. This investigation was conducted
in a small population with renal stones of 2–3 cm: Hyams
and Shah [59] found RIRS less expensive even after consid-
ering a higher number of retreatment and outpatient ser-
vice; on the other hand, PCNL provided superior stone
clearance.
Furthermore, the advent of miniaturised PCNL is chal-
lenging RIRS also in terms of cost effectiveness. In a match-
paired analysis between ultramini-PCNL (UMP) and RIRS for
renal stones ranging between 1 and 2 cm, Schoenthaler et al
[60] found the cost of RIRS as the only significant different
outcome in favour of the UMP because of the lower number
of disposables used.
Finally, a systematic review on cost effectiveness of
treatment modalities for upper urinary tract stone removal
failed to find relevant studies comparing RIRS versus SWL,
and identified only the abovementioned paper of Hyams
and Shah [59] for the comparison of RIRS versus PCNL;
accordingly, authors highlighted the need of properly
designed studies to better assess cost efficacy of treatment
modalities for renal stones [61].
4. Conclusions
RIRS is a well-established procedure under constant evolu-
tion with advances in technique and technology rapidly
evolving. It has gained worldwide popularity due to its
minimal invasiveness and outcomes, also in the setting of
patients unsuitable for other treatment modalities. Future
developments are likely to increase its cost effectiveness
and extend its use to a wider range of indications.
Author contributions: Francesco Sanguedolce had full access to all the
data in the study and takes responsibility for the integrity of the data and
the accuracy of the data analysis.
Study concept and design: Sanguedolce, de la Rosette.
Acquisition of data: Sanguedolce.
Analysis and interpretation of data: Sanguedolce, Bozzini, Chew, Kallidonis,
de la Rosette.
Drafting of the manuscript: Sanguedolce, Bozzini, Chew, Kallidonis, de la
Rosette.
Critical revision of the manuscript for important intellectual content:
Sanguedolce, de la Rosette.
Statistical analysis: Sanguedolce.
Obtaining funding: None.
Administrative, technical, or material support: None.
Supervision: de la Rosette.
Other: None.
Financial disclosures: Francesco Sanguedolce certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
53
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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