ENDOUROLOGY AND STONE DISEASE
The Fate of Residual Fragments After Retrograde Intrarenal Surgery in Long-Term Follow-up
Gokhan Atis1, Eyyup Sabri Pelit2, Meftun Culpan3*, Bilal Gunaydın1, Turgay Turan1, Yavuz Onur Danacioglu1,
Asif Yildirim1, Turhan Caskurlu1
Purpose: We aimed to describe the natural history of stone fragments ≤ 7 mm that remained after retrograde intra-
renal surgery (RIRS) in long-term follow-up.
Materials and Methods: We retrospectively reviewed 142 medical records of patients who had residual fragments
(RFs) ≤ 7 mm after RIRS. Patients were divided into 2 groups according to the size of RFs as ≤ 4 mm (group 1)
and 5 – 7 mm (group 2). Patients’ demographic data, stone characteristics, perioperative data and complications
were recorded. Re-growth of RFs, spontaneous passage, renal colic, infection and re-operation rates were our main
variables.
Result: A total of 142 patients (86 in group 1 / 56 in group 2) were followed for mean 54.45 ± 14.24 and 56.22 ±
10.28 months. Mean size of RFs was 2.85 ± 1.22 mm in group 1 and 6.81 ≤ 2.21 mm in group 2. Mean number of
RFs were 1.1 ± 0.2 in group 1 and 2.4 ± 1.6 in group 2 (P = .035). Spontaneous passage rate of RFs were 30.23%
and 17.85% in group 1 and 2, respectively (P = .032). No difference was observed in the re-growth rate of RFs
between the two groups (P = .094). Although no difference was observed in re-growth of RFs between the groups,
patients in group 2 were more likely to experience stone-related events such as renal colic and re-intervention rate
(P = .034, P = .029; respectively).
Conclusion: Our results demonstrate that RFs > 4 mm take higher risk in terms of stone-related events and should
be followed up more closely.
Keywords: natural history; renal stone; residual fragments; RIRS; spontaneous passage
INTRODUCTION
Retrograde intrarenal surgery (RIRS) have become a widely used modality with low complication and
high success in the treatment of kidney stones in recent
years.(1) Compared to extracorporal shockwave litho-
tripsy (ESWL), RIRS has higher success rate with less
pain in the treatment of renal stones ≤ 2 cm.(2) Because
of its low complication rate compared to the percutane-
ous nephrolithotomy (PCNL), indications of RIRS for
the treatment of renal stones have expanded for even
stones larger than 2 cm.(3-5). In the current literature,
stone free rate (SFR) of RIRS procedures were varying
between 73.6% and 94.1%; on the other hand, RF rates
after RIRS procedures range from 5.9% to 26.4%.(6)
Residual stone fragment (RF) is defined as the remain-
ing fragments after any surgical or non-surgical inter-
vention. RF which is asymptomatic, non-infectious,
non-obstructive and ≤ 4 mm in size is accepted as clin-
ically insignificant residual fragments (CIRF).(7,8) Stone
growth and recurrence, urinary tract infection, ureter-
ic obstruction are the potential complications of these
RFs.(9,10)
With the advancement of modern technologies, mini-
mally invasive methods such as ESWL, PCNL, RIRS
1Istanbul Medeniyet University, Goztepe Training and Research Hospital, Department of Urology, Istanbul,
Turkey.
2Harran University School of Medicine, Urology, Sanliurfa, TR.
3Sirnak Silopi State Hospital, Department of Urology, Silopi Sirnak, Turkey.
*Correspondence: Department of Urology, Silopi State Hospital, Sırnak, Turkey.
Tel: +90 544 4478995, E-mail: mculpan@gmail.com.
Received August 2017& Accepted April 2018
and laparoscopic procedures are all used more effec-
tively for the treatment of renal stones. However, RFs
after these minimally invasive procedures are still a
problem during the follow-up. In the literature, compli-
cation rates due to the RFs are varying between 18.1%
and 59% according to the performed procedures.(10,11) In
a prospective study published by Streem et al., 18.1%
of the fragments were experienced re-growth, 41.9% of
the residual fragments were not changed at all and 36%
spontaneous passage occurred within the first year af-
ter the ESWL procedure.(11) Altunrende et al. found that
22% of the patients who underwent PCNL operation
had residual fragments in a 3-year follow-up, 21.1% of
these RFs showed an increase in size, 71,1% of RFs
stayed stable or decreased in size and 7.9% patients
had spontaneous passage.(12) In the study of Ozgor et
al., 34% re-growth of CIRF was observed after RIRS
operation in 30-month follow-up period.(13)
In the literature, there are several studies about the natu-
ral course of CIRF after ESWL, URS, and PCNL; how-
ever, there are not enough clinical trials investigating
RF after RIRS.
In this study, we aimed to describe the natural history of
stone fragments smaller than 7 mm that remained after
RIRS procedures in long-term follow-up.
Vol 16 No 01 January-February 2019 1
MATERIALS AND METHODS
We retrospectively reviewed the medical records of
1048 patients who underwent RIRS at Istanbul Medeni-
yet University Goztepe Training and Research Hospital
from May 2008 to April 2016. Of them, 142 patients
who had ≤ 7 mm RF after RIRS procedures and at least
12 months follow-up were included into the study. The
patients who have asymptomatic residual fragments ≤
7 mm after the RIRS operation at 3 months postoper-
atively were included for the study. The patients who
had residual fragments > 7 mm accepted as a treatment
failure and excluded from the study. RFs were detected
with computed tomography (CT). The size of multiple
residual fragments apart from each other was measured
with sum of the long axis of each RF. The patients with
unsuccessful RIRS procedure and who required a re-
peated stone removal procedure within three months
postoperatively were excluded from the study (Figure
1). Gender, age, history of ESWL or stone surgery, and
comorbidities were recorded as patients’ characteris-
tics. Preoperative parameters such as stone diameter,
numbers, burden, laterality, location and opacity, a
presence of renal anomalies, grade of hydronephrosis
were evaluated with CT. Operation time, hospitaliza-
tion time, fluoroscopy time, postoperative complica-
tions, and number, burden, a location of RFs were also
recorded. Patients were divided into 2 groups according
to the size of RF as ≤ 4 mm and 5-7 mm. Re-growth
of RFs, spontaneous passage, renal colic, infection and
re-operation rates were main outcome variables.
Serum biochemistry, complete blood count, urine anal-
ysis and urine culture were performed for all patients
prior to surgery. All patients had sterile urine culture
prior to surgery. Urinary tract infection was treated ac-
cording to sensitivity results of the urine culture. The
procedures were performed in lithotomy position under
general anesthesia. We performed semi rigid ureteros-
copy firstly to create the ureteral dilation before placing
ureteral access sheath (UAS). 7.5 Fr flexible uretero-
scope (FLEX-X2, Tuttlingen, Germany) was advanced
through the 9.5 -11 fr UAS. The f - URS was passed over
the guidewire in the case of unsuccessful placement of
UAS. In all cases, 200 or 273 μm laser fiber was used
for stone fragmentation. Stones were fragmented into
pieces as small as possible and were left spontaneous
passage. At the end of the procedure, a double-J (4.7
fr) stent was inserted in all cases. Double-J stents were
removed 2 - 4 weeks after the operation.
Table 1. Patient demographics, preoperative and perioperative findings.
≤ 4 mm 5-7 mm
Mean age (year) 45.4 ± 16.6 39.2 ± 11.4 P = .247
Gender (male/female) 58/28 24/32 P = .437
Stone opacity (opaque/non-opaque) 72/14 46/10 P = .894
Stone size before RIRS (mm) 16.36 ±7.1 22.08 ± 7.5 P = .028
Stone number 1.14 ± 0.4 1.86 ± 1.8 P = .046
Hydronephrosis P = .595
None 32 20
Grade 1 26 18
Grade 2 14 12
Grade 3 14 6
Operation time (min) 41.17 ± 14.23 56.21 ± 20.17 P = .044
Fluoroscopy time (min) 3.02 ± 2.34 3.22 ± 4.07 P = .760
Hospitalization time (day) 1.68 ± 2.95 1.81 ± 3.04 P = .685
Mean follow-up (month) 54.45 ± 14.24 56.22 ± 10.28 P =. 087
Data is presented as mean ± SD or number (percent)
≤ 4 mm 5-7mm
Mean RF burden (mm) 2.85 ± 1.22 6.81 ± 2.21 P = .004
Mean RF number 1.1 ± 0.2 2.4 ± 1.6 P = .035
Spontaneous passage 26/86 (30.23%) 10/56 (17.85) P = .032
Lower pole 6/36 (16.6%) 2/18 (11.1%)
Middle/upper pole 10/32 (31.25%) 2/22 (9.09%)
Multiple calix 4/8 (50%) 2/10 (20%)
Renal pelvis 6/10 (60%) 4/6 (66.6%)
Re-growth 18 (20.93%) 12 (21.42%) P = .094
Lower pole 7 5
Middle/upper pole 4 3
Multiple calix 7 4
Renal pelvis - -
Renal Colic 24 (27.90% ) 8 (14.28%) P = .034
Urinary infection 6 (6.97%) 4 (7.14%) P = .083
Re-operation 16 (18.60%) 18 (32.14%) P = .029
ESWL 8 8
PCNL 0 2
f-URS 4 4
URS 2 4
DJ stent insertion and delayed URS because of urosepsis 2 0
Data is presented as mean ± SD or number (percent)
Table 2. RF characteristics and postoperative follow-up data.
Fate of residual fragments after RIRS – Atis et al.
Endourology and Stone Diseases 2
Vol 16 No 01 January-February 2019 3
We performed CT in the 3rd months of follow-up. Pa-
tients were accepted as stone-free when there was no
residual fragments on CT on follow-up. The frequency
of visits and imaging methods (CT / ultrasonography
or kidney-ureter-bladder x-ray) to be used in each visit
was determined according to RF burden, localization,
and the presence of obstruction and symptoms of pa-
tients during the follow-up. If the patient had RF and
was asymptomatic, CT scan performed yearly. If avail-
able, stone analyses were done and all patients under-
went a metabolic evaluation at 1 month postoperative-
ly. Dietary suggestions were made for all patients and
if necessary patients treated with appropriate medical
treatment according to metabolic evaluation or stone
analysis.
Statistical analyses were performed via SPSS software,
version 21.0 (IBM, Armonk, NY). The data were ex-
pressed as the mean ± standard deviation or frequency.
The Kolmogorov-Smirnov test was used to test the nor-
mal distribution of the variables. The categorical varia-
bles were compared with the Chi squared test, and the
continuous variables were compared with an unpaired t
test or the Mann–Whitney U test. A p value ≤ 0.05 was
considered to be significant.
RESULTS
In our study RF rate was detected %13.54 (142 / 1048).
A total of 142 patients (86 in group 1 / 56 in group 2)
were followed for a mean of 54.45 ± 14.24 and 56.22 ±
10.28 months respectively. Mean stone size and number
before the operation were 16.36 ± 7.1 mm and 1.14 ±
0.4 in group 1, 22.08 ± 7.5 mm and 1.86 ± 1.8 in group
2, respectively (P = .028 / P = .046). The pre-operative
and operative characteristics of patients were summa-
rized in Table 1.
Mean size was 2.85 ± 1.22 mm in group 1 and 6.81±
2.21 mm in group 2. Mean number of RFs was 1.1 ± 0.2
in group 1 and 2.4 ± 1.6 in group 2 (p = .035). Spon-
taneous passage rate of RFs were 30.23% and 17.85%
in group 1 and 2, respectively (P = .032). No differenc-
es were observed in the re-growth rate of RFs between
the two groups (P = .094). Although no difference was
observed in re-growth rate between the two groups, pa-
tients in group 2 were more likely to experience stone
related events such as renal colic and re-intervention (P
= .034, P = 0.029; respectively). A total of 16 patients
in group 1 and 18 patients in group 2 needed additional
procedures (Table 2).
The stone analysis was available for 60 and 40 patients
in group 1 and 2, respectively. The stone analysis re-
sults are shown in Table 3.
DISCUSSION
RFs that are asymptomatic, non-infectious, non-ob-
structive and in ≤ 4 mm size is generally accepted as
CIRF.(7) This term is not accepted as an innocent defi-
nition by some authors because almost 59% of these
fragments require re-admission to the hospital.(10) How-
ever, there are not enough studies evaluating the natural
course of RFs after endourological procedures. Herein
we both evaluated the natural course of RFs after the
RIRS procedures in long-term follow-up and also com-
pared RFs according to the size in terms of spontaneous
passage, stone-related events and re- intervention rates.
There are several studies describing the natural course
of RFs after PCNL and ESWL. High stone burdens,
multiple access requirements, stone location in differ-
ent calyces, restriction of visualization due to hemor-
rhage during the operation were some of the reasons
of the RFs after PCNL. Fragmentation technique in
PCNL (ultrasonic or pneumatic) was another reason of
the high RFs rates according to some studies.(14,15) But,
conversely to these studies in a prospective research
Radfar MH et al reported that there were no statistically
significant differences in RFs rates between pneumatic
and ultrasonic lithotripsy.(16)
In a study conducted by Ganpule et al., 7.57% RF was
observed and, 65.47% of these RFs spontaneously pas-
saged after 3 months. They found that RFs smaller than
25 mm2 and the renal pelvis localization had the highest
chance of spontaneous passage.(6) Raman et al. report-
ed 8% RFs rate in the patients who underwent PCNL
procedure.(17) 42.8% of patients with residual fragments
were found to have stone-related symptoms during the
follow-up and 26% of these patients required second-
ary intervention. The rate of symptomatic attack and
secondary intervention due to residual fragment was
found to be higher in stones localized in renal pelvis
and ureter and in patients with RF greater than 2 mm.(17)
In our study, similarly to the literature regarding natu-
ral course of RFs after PCNL, spontaneous passage rate
was higher in patients with RFs smaller than 4 mm and
RFs located in the renal pelvis. Moreover, the re-inter-
vention rate was higher in RFs larger than 4 mm.
The rate of residual fragment detection after ESWL
procedures is still quite high. It is proved that the
stones larger than 20 mm, increased stone number, cys-
tine-brushite-calcium oxalate monohydrate stone types
were the negative predictive factors that affect the RF
Table 3. Stone analysis results.
Stone Analysis Results ≤ 4 mm 5-7 mm
Unknown 26 (30.23%) 16 (28.57%)
Ca oxalate/phosphate 28 (32.55%) 18 (32.14%)
Uric acid 8 (9.30%) 4 (7.14%)
Cystine 6 (6.97%) 8 (14.28%)
Struvite 6 (6.97) 2 (3.57%)
Mixed 12 (13.95%) 8 (14.28%)
Figure 1. Trial flow diagram
Fate of residual fragments after RIRS – Atis et al.
rates after ESWL procedures.(18,19) In the literature, stone
events due to RF after ESWL procedures have been re-
ported between 18.1% and 59%.(10,11) In a prospective
study published by Streem et al., 160 patients with RFs
were followed up for 89 months and re-growth of RFs
was detected in 18.1% of these patients, 41.9% of the
RFs were unchanged and spontaneous passages was
observed in 36%.(11) In contrary to the reported natural
course of RFs after ESWL, re-intervention rates in our
study were lower in even RFs ≤ 4 mm group than the
reported re-intervention rates after ESWL. We thought
that higher spontaneous passage rates after RIRS com-
pared to ESWL may be due to passive ureteral dilata-
tion effect of Double-J stent insertion after RIRS.
Since RIRS is a new treatment modality, there are not
enough studies in the literature regarding the fate of
RFs after the RIRS procedures. Ozgor et al. reported a
34% re-growth rate in 44 patients in 30-month of fol-
low-up period.(13) Rebuck et al. showed that 19.6% of
the patients with RFs had a stone-related attack in 19.9
months of follow-up period.(20) In a study conducted by
Chew et al. with the participation of 6 centers, the data
of 232 patients with RF after RIRS were retrospectively
reviewed.(21) Fifty six percent of these patients did not
need additional intervention and remained asymptomat-
ic, 15% had experienced a stone-related attack without
a need of additional intervention and 29% had under-
gone an additional intervention.
Moreover, patients with RF larger than 4 mm were
found to have a higher risk of recurrence and stone re-
lated events. Similar to these studies, in our study, we
detected a positive correlation between the RF size and
the re-intervention rate. However, there was no statis-
tically significant difference in growth rate between
the two comparison groups of RF size. This may be
explained by the follow-up with appropriate medical
treatment.
Pelvicalyceal anatomy and the calyceal localization
of the RFs are well-known factors that may affect the
spontaneous passage rate. Several studies have shown
lower clearance rates in RFs located in the lower cal-
yces than in the middle and/or upper calyces.(22,23) In
contrast, Rebuck et al. reported that there was no differ-
ence in the spontaneous passage rates between the RFs
located in lower and non-lower pole.(20) In our study, we
observed the highest spontaneous passage rates in renal
pelvis than the other calyceal localizations.
Different fragmentation techniques such as dusting
and drilling have been used to treat renal stones uret-
eroscopically. Chew et al. found that patients treated
with dusting techniques had a shorter time to a subse-
quent stone event than patients treated with drilling and
basketing technique.(21) In our study group, stones were
fragmented into pieces as small as possible and were
left spontaneous passage. The superiority of a frag-
mentation technique over the other technique has not
been proven yet in terms of the natural course of RFs.
(24) Further studies are needed to compare the fragmenta-
tion techniques to determine the effect of fragmentation
technique over the natural course of RFs.
Our study has some limitations. The main limitation of
the study is its retrospective nature, which may result in
differences in follow-up protocol such as frequency of
visits and used imaging methods. In addition, despite
the same surgical and fragmentation techniques were
used in all cases, different surgeons were involved in
the procedures. Lastly in our study all patients had re-
ceived dietary instructions and some of them specific
medical treatment. This might affect the re-growth rate
and the absence of difference between the two groups
regarding growth rate might have been the result of the
specific medical treatment.
Despite these limitations, the present study is one of
the largest series in the English literature and has the
longest follow-up period, which evaluates the natural
course of RFs.
CONCLUSIONS
Our results demonstrate that vast majority of RFs ≤
4mm passed spontaneously or remained unchanged.
However spontaneous passage rates of RFs in 5 - 7 mm
in size were lower and re-intervention rates were higher
than RFs ≤ 4 mm in size. Moreover, there were no sta-
tistically significant differences in re-growth rates and
urinary tract infections between the RFs ≤ 4 mm and
5 - 7 mm. Taken together, our results suggest that RFs
larger than 4 mm take higher risk in terms of stone-re-
lated events and should be followed up more closely.
CONFLICT OF INTEREST
The authors declare that they have no conflict of inter-
est.
REFERENCES
1. Van Cleynenbreugel B, Kilic O, Akand M.
Retrograde intrarenal surgery for renal stones
- Part 1. Turk J Urol. 2017;43:112–21.
2. Javanmard B, Kashi AH, Mazloomfard
MM, Jafari AA, Saeed A. Retrograde
Intrarenal Surgery Versus Shock Wave
Lithotripsy for Renal Stones Smaller Than
2 cm: A Randomized Clinical Trial. Urol J.
2016;13:2823–8.
3. Atis G, Culpan M, Pelit ES, et al. Comparison
of percutaneous nephrolithotomy and
retrograde intrarenal surgery in treating 20-40
mm renal stones. Urol J. 2017;14:2995-9.
4. Karakoc O, Karakeci A, Ozan T, et al.
Comparison of retrograde intrarenal surgery
and percutaneous nephrolithotomy for the
treatment of renal stones greater than 2 cm.
Turk J Urol. 2015;41:73–7.
5. De S, Autorino R, Kim FJ, et al. Percutaneous
nephrolithotomy versus retrograde intrarenal
surgery: A systematic review and meta-
analysis. Eur Urol. 2015;67:125–37.
6. Ganpule A, Desai M. Fate of residual stones
after percutaneous nephrolithotomy: a critical
analysis. J Endourol. 2009;23:399–403.
7. Candau C, Saussine C, Lang H, Roy C, Faure
F, Jacqmin D. Natural history of residual
renal stone fragments after ESWL. Eur Urol.
2000;37:18–22.
8. Delvecchio FC, Preminger GM. Management
of residual stones. Urol Clin North Am.
2000;27:347–54.
9. Osman MM, Alfano Y, Kamp S, et al.
5-year-follow-up of patients with clinically
Fate of residual fragments after RIRS – Atis et al.
Endourology and Stone Diseases 4
Vol 16 No 01 January-February 2019 5
insignificant residual fragments after
extracorporeal shockwave lithotripsy. Eur
Urol. 2005;47:860–4.
10. Khaitan A, Gupta NP, Hemal AK, Dogra
PN, Seth A, Aron M. Post-ESWL, clinically
insignificant residual stones: reality or myth?
Urology. 2002;59:20–4.
11. Streem SB, Yost A, Mascha E. Clinical
implications of clinically insignificant stone
fragments after extracorporeal shock wave
lithotripsy. J Urol. 1996;155:1186–90.
12. Altunrende F, Tefekli A, Stein RJ, et al.
Clinically insignificant residual fragments
after percutaneous nephrolithotomy: medium-
term follow-up. J Endourol. 2011;25:941–5.
13. Ozgor F, Simsek A, Binbay M, et al. Clinically
insignificant residual fragments after flexible
ureterorenoscopy: medium-term follow-up
results. Urolithiasis. 2014;42:533–8.
14. Zengin K, Sener NC, Bas O, Nalbant I, Alisir
I. Comparison of pneumatic, ultrasonic and
combination lithotripters in percutaneous
nephrolithotripsy. Int Braz J Urol.
2014;40:650–5.
15. Karakan T, Diri A, Hascicek AM, Ozgur
BC, Ozcan S, Eroglu M. Comparison of
ultrasonic and pneumatic intracorporeal
lithotripsy techniques during percutaneous
nephrolithotomy. Sci World J. 2013;2013:10–
3.
16. Radfar MH, Basiri A, Nouralizadeh A, et
al. Comparing the Efficacy and Safety of
Ultrasonic Versus Pneumatic Lithotripsy
in Percutaneous Nephrolithotomy : A
Randomized Clinical Trial. Eur Urol Focus.
2017;3:82–8.
17. Raman JD, Bagrodia A, Gupta A, et al. Natural
history of residual fragments following
percutaneous nephrostolithotomy. J Urol.
2009;181:1163–8.
18. Skolarikos A, Mitsogiannis H, Deliveliotis C.
Indications, prediction of success and methods
to improve outcome of shock wave lithotripsy
of renal and upper ureteral calculi. Arch Ital
Urol Androl. 2010;82:56–63.
19. Cicerello E, Merlo F, Maccatrozzo L.
Management of Clinically Insignificant
Residual Fragments following Shock Wave
Lithotripsy. Adv Urol. 2012;2012:320104.
20. Rebuck DA, Macejko A, Bhalani V, Ramos P,
Nadler RB. The natural history of renal stone
fragments following ureteroscopy. Urology.
2011;77:564–8.
21. Chew BH, Brotherhood HL, Sur RL, et al.
Natural History, Complications and Re-
Intervention Rates of Asymptomatic Residual
Stone Fragments after Ureteroscopy: a Report
from the EDGE Research Consortium. J Urol.
2016;195:982–6.
22. Drach GW, Dretler S, Fair W, et al. Report
of the United States cooperative study of
extracorporeal shock wave lithotripsy. J Urol.
1986;135:1127–33.
23. Psihramis KE, Jewett MA, Bombardier C,
Caron D, Ryan M. Lithostar extracorporeal
shock wave lithotripsy: the first 1,000
patients. Toronto Lithotripsy Associates. J
Urol. 1992;147:1006–9.
24. Ghani KR, Wolf JSJ. What is the stone-free
rate following flexible ureteroscopy for kidney
stones? Nat Rev Urol. 2015;12:281–8.
Fate of residual fragments after RIRS – Atis et al.