- Email: [email protected]
Percutaneous Nephrolithotomy vs Retrograde Intrarenal Surgery for Large Renal Stones in Pediatric Patients: A Randomized Controlled Trial
Author's Accepted Manuscript Percutaneous Nephrolithotomy (PCNL) Versus Retrograde Intra-renal Surgery (RIRS) in Treatment of Large Renal Stones (>2cm) In Pediatric Patients: A Randomized Controlled Trial Karim S.M. Saad , Mohamed Elsaid Youssif , Seif Al Islam Nafis Hamdy , Ahmed Fahmy , Ahmed Gamal El Din Hanno , Ahmed R. EL-Nahas PII: DOI: Reference:
S0022-5347(15)04328-1 10.1016/j.juro.2015.06.101 JURO 12751
To appear in: The Journal of Urology Accepted Date: 2 June 2015 Please cite this article as: Saad KSM, Youssif ME, Hamdy SAIN, Fahmy A, Hanno AGED, EL-Nahas AR, Percutaneous Nephrolithotomy (PCNL) Versus Retrograde Intra-renal Surgery (RIRS) in Treatment of Large Renal Stones (>2cm) In Pediatric Patients: A Randomized Controlled Trial, The Journal of Urology® (2015), doi: 10.1016/j.juro.2015.06.101. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
ACCEPTED MANUSCRIPT
Percutaneous Nephrolithotomy (PCNL) Versus Retrograde Intra-renal Surgery (RIRS) in Treatment of Large Renal Stones (>2cm) In Pediatric Patients: A Randomized Controlled Trial 1
1
1
1
RI PT
Karim S.M. Saad , Mohamed Elsaid Youssif , Seif Al Islam Nafis 1
R. EL-Nahas
2
From
2
Urology Department, Alexandria Faculty of Medicine
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1
SC
Hamdy , Ahmed Fahmy , Ahmed Gamal El Din Hanno , and Ahmed
Urology Department, Urology and Nephrology Center, Mansoura University
Keywords: Percutaneous Neprolithotomy; Retrograde intrarenal surgery;
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Flexible ureteroscopy; Renal calculi; Stones; Pediatric; Children Word Count: 2027 (Introduction through conclusion) Corresponding author:
EP
Karim S.M. Saad
Lecturer of Urology
AC C
Urology Department
Faculty of Medicine, Alexandria University Address: 25 Victor Emanuel square, Smouha, Alexandria, Egypt Tel: +201227887221 Email: [email protected]
ACCEPTED MANUSCRIPT
ABSTRACT Purpose: To compare the outcomes of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in treatment of children with >2 cm renal calculi. Patients and Methods: Between May 2011 and February 2014, 38 pediatric patients
RI PT
(<16 year-old) with renal calculi > 2cm were randomized between PCNL and RIRS. Demographic data, stone criteria, operative technique, radiation time, complications, blood transfusion, hemoglobin drop, stone free rates and hospital stay were compared between both groups. Stone free was document if there were no residual stones after
SC
one month.
Results: The study included 43 renal units; 21 units in RIRS group and 22 units in
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PCNL group. Operative time was comparable for both groups. The mean radiation time and hospital stay were longer after PCNL (P<0.001). The stone free rate of RIRS monotherapy was significantly lower than PCNL monotherapy (71% vs 95.5%, P=0.046). Patients in PCNL group had a statistically significant more complication rate compared with RIRS group (P=0.018). Three patients in the PCNL group received blood transfusions, whereas none of the children in the RIRS group needed
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blood transfusion (P=0.015).
Conclusion: For treatment of large or complex renal stones in pediatric patients, PCNL monotherapy had the advantage of better stone free rate while RIRS had the
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EP
advantages of lesser radiation exposure, complications and hospital stay.
2
ACCEPTED MANUSCRIPT
INTRODUCTION Urolithiasis in pediatric patients has greater incidence in third world nations than developed countries due to malnutrition, metabolic abnormalities, environmental or dietary factors
(1,2)
. Historically, large and staghorn stones in children have been
treated with open procedures with considerable morbidity and lengthy convalescence.
RI PT
Surgical management of urolithiasis in children has evolved dramatically after the advent of shock wave lithotripsy (SWL) and it is currently the procedure of choice in treating most small upper tract calculi in children (3). Certainly, this offers tremendous advantages over open stone procedures, especially for small stones. However, not all
SC
stones are amenable to this treatment.
In the modern era of minimally invasive surgery, treatment of urolithiasis has
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been revolutionized with the advent of endoscopic techniques and improved technology (4). The introduction of percutaneous nephrolithotomy (PCNL) offered a new approach for these difficult stones. Major concerns regarding PCNL in children have been the size of the instruments in relation to patient size, blood loss, and mobile, smaller kidneys. It was reported that PCNL was efficacious, less invasive than open surgery, and it should be performed more often in the pediatric population .
TE D
(4, 5)
Following the advances in endoscopic instruments and development of smaller endoscopes and effective energy sources for stone disintegration, ureteroscopic management has become increasingly applicable in pediatric stone patients
(6)
.
EP
Although technological advances have resulted in ureteroscopic equipment that can be used in the urinary tract of children, caution must be exercised. The margin for
AC C
error is small, and the urologic surgeon must be familiar with the equipment, ureteroscopic techniques, and their limitations. The long-term consequences of ureteral endoscopic manipulations in the pediatric population remain undefined. Debate continues regarding the most efficacious modality for large renal
calculi in children. This study was conducted to compare the outcomes of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in treatment of children with >2 cm renal calculi.
3
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PATIENTS AND METHODS The study protocol was approved by the local ethical committee and it was conducted between May 2011 and February 2014 in urology department, Alexandria university hospital. Inclusion criteria were pediatric patients (<16 year-old) who have renal calculi larger than 2 cm. Exclusion criteria were uncorrected bleeding diathesis,
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renal insufficiency, congenital renal anomalies (such as horse shoe and ectopic kidneys) and contraindications to general anesthesia. The parents of included patients have signed an informed consent. Eligible patients were randomized using sealed closed envelopes between PCNL and RIRS.
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Preoperative workup:
All patients were evaluated with history taking, routine laboratory
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investigations; urinalysis, culture and sensitivity, complete blood count (CBC), coagulation profile and creatinine. Radiological evaluation included; plain abdominal radiography (KUB) and gray-scale ultrasonography (US). Non-contrast CT was performed for quantitative assessment of the stone burden and location. Technique of RIRS:
All procedures were done in lithotomy position under general anesthesia.
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Prophylactic antibiotics were administrated according to the child weight. Ureteroscopy was performed using 4.5 French (F) semirigid ureteroscope (Richard Wolf ®, Knittlingen, Germany). Then a second guidewire was introduced. A flexible ureteroscopy FlexX2 (Karl Storz Endoscopey, Tuttlingen, Germany) was through a
EP
ureteral access sheath (9.5-11.5 F) to minimize intrarenal pressure along the procedure. In cases of access sheath introduction failure, a JJ stent was left for passive
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dilatation of the ureter, and the patient was readmitted after 10 days for the procedure. Holmium: YAG laser was used for stone disintegration at energy of 0.4-0.6 Joules and pulse rate of 10-15 Hertz. Stones were fragmented into powder and smaller pieces without any trial for gravels removal. A 4.8F ureteral stent was left for 2-4 weeks after intervention. Technique of PCNL: All cases were done in prone position under general anesthesia. Contrast material was injected through a ureteric catheter for opacification of the collecting system. Renal puncture was performed under fluoroscopic guidance. Dilatation of the
4
ACCEPTED MANUSCRIPT tract was done using Alken’s metal dilators up till 22 F. A 17 Fr pediatric nephroscope (Karl Storz Endoscopey, Tuttlingen, Germany) was used in all cases. Pneumatic lithotripsy was used for stone disintegration. A Flexible Nephroscope (Gyrus-ACMI (ACN-2), Southborough, MA) was used for extraction of residual stones with basket at the end of the procedure. Putting a nephrostomy tube or not was
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dictated by intraoperative events and according to each case individually. A nephrostomy tube was placed if there were intraoperative complications or there were significant residuals. A 4.8F ureteral stent was left for 2-4 weeks after intervention. Postoperative evaluation and follow-up:
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Stones retrieved at the end of the procedures were examined by infrared spectroscopy. KUB and ultrasonography were performed before discharge and after
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one month. Non-contract spiral CT was used in radiolucent stones. All ureteral stents were removed on outpatient bases. The stone free of each treatment as monotherapy was conferred by the absence of any stone fragments in follow up imaging. Statistical analysis:
Demographic data, stone criteria (number, length, and burden), operative technique, radiation exposure time, complications, blood transfusion, stone free rate
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and hospital stay were recorded and compared between both groups. Chi-square test was applied to compare categorical data. Mann-Whitney U test
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or t-test was used to compare continuous data as appropriate.
5
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RESULTS The study included 38 patients (43 renal units); 21 renal units in RIRS group and 22 renal units in PCNL group. Boys represented 66.7% of RIRS group and 63.6% in PCNL group (p=0.835). As shown in table 1, stones characters and operative time
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were comparable for both groups. The mean radiation time was longer in PCNL group (P<0.001) and hospital stay was also longer after PCNL (P<0.001).
Immediate conversion to PCNL was needed in 2 patients in RIRS group because the stones were not accessible with the ureteroscope (lower calyx stones).
SC
These 2 patients were included in RIRS group and considered as failure. A second session was needed in 2 patients (9.5%) in RIRS group and one patient (4.5%) in PCNL group. Follow-up was elected for 4 patients in RIRS group and one patient in
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PCNL group with small residual stones <4mm. The stone free rate of RIRS monotherapy was significantly lower than PCNL monotherapy (71% vs 95.5%, P=0.046). The efficiency quotient was 0.65 in RIRS and 0.95 in PCNL. Patients in PCNL group had a statistically significant more complication rate compared with RIRS group (P=0.018). Only 2 patients (9.5%) in RIRS group
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encountered pyrexia (<39oC). Fever was controlled by intravenous antibiotics and antipyretics. In PCNL group, 3 patients had intraoperative bleeding that required blood transfusion, one patient had ileum injury necessitated open repair and one patient with a supracostal puncture developed hydrothorax that was resolved
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spontaneously without chest tube placement. Modified Clavien classification of the complications is presented in table 1. Postoperative Hemoglobin drop was more in
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PCNL group (P=0.012).
6
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DISCUSSION The ultimate objective of stone therapy is to render the patient stone free. This is particularly crucial in the pediatric population that is by default considered high risk for recurrence. The importance of post-treatment stone-free status in children was demonstrated by Afshar et al who showed that 69% of the children with residual
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fragments ≤ 5 mm up to 48 months after SWL had symptomatic episodes or increase in stone size (7). This feature of pediatric stone disease should be factored in the choice of treatment modality.
SC
In children, RIRS lagged behind its use in adults owing to the initial unavailability of small instruments, coupled by the plethora in SWL in the 1980s. However, SWL was not the best choice in in stone burden ≥2 cm
(8)
The main
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drawback of SWL is that up to 75% of the patients would require multiple sessions (9). On the other hand, PCNL has a role in larger stone burden, complex and staghorn calculi, and after failed SWL
(10-12)
. The overall stone-free rate of our
pediatric series was 95.5% after PCNL procedure. These results are within the
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previously reported range of 67%-100%.
The Children’s Hospital of Philadelphia reported the largest case series utilizing flexible pediatric ureteroscopy
(6)
with RIRS used to manage 101 renal stones (87
lower polar). This study shows a success rate of 97% for calculi larger than 1 cm.
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However, it is noteworthy that access was not possible in the first surgery for 59% of the patients, raising concerns for additional anesthesia for more than half of their
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patients. The stone free rate in our patients was lower (71%), but the stone burden was considerably larger. Tanaka et al
(13)
reported their 5-year experience in pediatric
RIRS, Interestingly, initial stone-free status depended on pre-operative stone size (P=0.005). The younger patient age (P=0.04) and larger pre-operative stone size (P=0.002) influenced the need for extra procedures. The key result of the present study is that it showed lower stone free rates of RIRS versus PCNL for treatment of large, multiple and complex renal stones in children (P=0.046). However, PCNL remains more invasive with more incidence of complications than RIRS (41% versus 9.5%, P=0.018). Moreover, PCNL was associated with more severe complications. Bleeding was the most prominent
7
ACCEPTED MANUSCRIPT complication in our series of PCNL as 3 out of the 22 patients had intraoperative bleeding (13.6%) that required blood transfusions. Zeren et al reported 24% incidence of hemorrhage requiring transfusion (10). On the other hand, no patients required blood transfusion in the RIRS group. Desai et al
(11)
reported 1.6 g/dl fall in hemoglobin
after PCNL. In the present study, mean hemoglobin deficit was significantly lower is
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RIRS group (1.6 versus 3.1gm/dl, P=0.012). The higher incidence of bleeding complications in the present study may be attributed to the size of tract dilatation (22F)
(14)
. We used this sheath size to allow extraction of larger stone fragments.
Recent series encourage the adoption of ultra-mini-perc and micro-perc for treatment
large and complex stone burden was not reported.
SC
of small renal stones in pediatric patients (15). However, the use of these techniques in
(16)
. In
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Chest complications are known after supracostal percutaneous access
current series seven patients needed a supracostal puncture for access to either a staghorn stone or stone located in upper calyx. One of them (14%) developed hydrothorax. In another series Anand et al reported that 13 patients required a supracostal puncture. Hydrothorax developed in one patient with supracostal puncture necessitating tube drainage
(17)
. Certain measures should be taken while performing
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supracostal punctures. First, the supra 11th rib approach is better to be avoided because of the higher incidence of pleural and pulmonary violation. The use of an Amplatz sheath, which should be well positioned, reduces the risk of symptomatic hydrothorax by allowing free exit of irrigant. Additionally, intra-operative chest
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fluoroscopy at the end of the procedure is beneficial to identify a fluid collection (16). Adjacent visceral injuries are another potential complication of percutaneous (18; 19)
. Early diagnosis is crucial for management and to decrease
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nephrolithotomy
morbidity for the patient. In current series, we reported one who encountered ileum injury (20).
No doubt, there is an increasing trend in the adoption of RIRS in the
management of renal stones in children. This has been facilitated by both the rapidly evolving technology and the particular drawbacks that are associated with SWL and PCNL. The initial concerns of increased risks and complications associated with ureteroscopic manipulation of the delicate ureteral orifices and ureters of children do not seem to be substantiated in the literature. However, a limited and a non-uniform
8
ACCEPTED MANUSCRIPT reporting in the literature of the outcome of RIRS in children, making the surgeon's experience of principal importance in counseling and offering treatment to children with renal stones. Other advantages of RIRS in the present study are the shorter radiation exposure time and hospital stay. It is very important to reduce radiation exposure during
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treatment of calculi in children because they are susceptible to multiple recurrences and repeated treatments.
The main limitation of this study is the small sample size that may lead to type
SC
II statistical error. Therefore, the difference between stone free rates in the two groups did not reach statistical significance. However, including a sufficient number of pediatric patients with large renal calculi is difficult. Other randomized trials with
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larger number of patients are required.
CONCLUSION
For treatment of large or complex renal stones in pediatric patients, PCNL
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monotherapy had the advantage of better stone free rate while RIRS had the
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advantages of lesser radiation exposure, complications and hospital stay.
9
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References 1.
Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004; 15: 3225-31.
2.
Saxena A, Sharma RK. Nutritional aspect of nephrolithiasis. Indian J Urol.
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2010; 26: 523-30. 3.
Raza A, Turna B, Smith G, Moussa S, Tolley DA: Paediatric urolithiasis: 15 years of local experience with minimally invasive endourological management of paediatric calculi. J Urol 2005; 174:682–685.
Desai M: Endoscopic management of stones in children. Cur Opin Urol
SC
4.
2005; 15: 107-112. 5.
Kumar R, Anand A, Saxena V, Seth A, Dogra PN, Gupta NP: Safety and
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efficacy of PCNL for management of staghorn calculi in pediatric patients. J Pediatr Urol 2011; 7: 248-251. 6.
Kim SS, Kolon TF, Canter D, White M, Casale P. Pediatric flexible ureteroscopic
lithotripsy:
the
children’s
hospital
of
Philadelphia
experience. J Urol 2008; 180:2616-9
Afshar K, McLorie G, Papanikolaou F, et al.: Outcome of small residual
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7.
stone fragments following shock wave lithotripsy in children. J Urol 2004, 172:1600–3. 8.
Muslumanoglu AY, Tefekli A, Sarilar O, Binbay M, Altunrende F,
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Ozkuvanci U. Extracorporeal shock wave lithotripsy as first line treatment alternative for urinary tract stones in children: a large scale retrospective
9.
AC C
analysis. J Urol. 2003; 170: 2405-8 Aksoy Y, Ozbey I, Atmaca AF, Polat O. Extracorporeal shock wave lithotripsy in children: experience using a mpl-9000 lithotriptor. World J Urol. 2004; 22: 115-9.
10.
Zeren S, Satar N, Bayazit Y, Bayazit AK, Payasli K, Ozkeçeli R. Percutaneous nephrolithotomy in the management of pediatric renal calculi. J Endourol. 2002; 16:75–8.
11.
Desai
MR,
Kukreja
RA,
Patel
SH,
Bapat
SD.
Percutaneous
nephrolithotomy for complex pediatric renal calculus disease. J Endourol. 2004; 18:23–7.
10
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Ozden E, Sahin A, Tan B, et al. Percutaneous renal surgery in children with complex stones. J Pediatr Urol. 2008; 4:295-298.
13.
Tanaka ST, Makari JH, Pope JC, 4th, Adams MC, Brock JW, 3rd, Thomas JC. Pediatric ureteroscopic management of intrarenal calculi. J Urol. 2008; 180: 2150–3. Yamaguchi A, Skolarikos A, Buchholz NP, et al; Clinical Research Office
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14.
Of The Endourological Society Percutaneous Nephrolithotomy Study Group: Operating times and bleeding complications in percutaneous nephrolithotomy: a comparison of tract dilation methods in 5,537 patients
SC
in the Clinical Research Office of the Endourological Society Percutaneous Nephrolithotomy Global Study. J Endourol 2011; 25: 933-9 15.
Ganpule AP1, Bhattu AS, Desai M. PCNL in the twenty-first century: role
16.
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of Microperc, Miniperc, and Ultraminiperc. World J Urol 2015; 33: 235-40 El-Nahas AR, Shokeir AA, El-Kenawy MR, Shoma AM, Eraky I, ElAssmyAM, Ghaly AM, El-Kappany HA. Safety and efficacy of supracostal percutaneous nephrolithotomy in pediatric patients. J Urol. 2008;180: 676-80
Anand A, Kumar R, Dogra PN, Seth A, Gupta NP. Safety and efficacy of a
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17.
superior calyceal puncture in pediatric percutaneous nephrolithotomy. J of Endourol 2010; 24: 1725-8. 18.
Bhageria A, Nayak B, Seth A, Dogra PN,
Kumar R. Pediatric
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percutaneous nephrolithotomy: Single-centre 10-year experience. J Ped Urol 2013: 9: 472-5.
Goger E, Guven S, Gurbuz R, Yilmaz K, Kilinc M, Ozturk A. Management of a
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19.
colon perforation during pediatric percutaneous nephrolithotomy. J Endourol. 2012; 26:1118-20.
20.
Saad KS, Hanno A, El-Nahas AR. Injury of the ileum during percutaneous nephrolithotomy in a pediatric patient. Can Urol Assoc J. 2014; 8: 204-6.
11
Table 1: Comparison between the RIRS and PCNL for treatment of large renal stones (>2
RIRS (n=21)
PCNL (n=22)
Right
9 (42.9)
10 (45.5)
Left
12 (57.1)
12 (54.5)
6.44 (4.84)
6.93 (3.55)
5 (1.67-16.0)
8 (1.42-13.0)
Mean (SD)
79.5 (29.4)
69.8 (29.6)
Median (Range)
85 (30–135) 1.6 (0.8)
SC
ACCEPTED MANUSCRIPT cm) in pediatric patients:
1.5 (1.0–4.0)
3.0 (2.0 – 6.0)
0.53 (0.35)
1.60 (1.43)
0.45 (0–1.3)
1.40 (0.5-5)
1.1 (0.52)
2.59 (1.98)
1.0 (0.50–2.0)
2.0 (1.0–9.0)
P Value
Stone side 0.864
Mean (SD) Median (Range)
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Age (years)
Operative time (min)
Mean (SD) Median (Range) Hemoglobin Deficit (g/dl) Mean (SD) Median (Range) Mean (SD)
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Hospital stay (days) Median (Range)
No.
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EP
Stone Burden Single Multiple Staghorn
3.1 (1.1)
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Radiation time (min)
70 (15–140)
%
No.
0.710
0.285
<0.001
0.012
<0.001
% 0.218
5
23.8
2
9.1
11
52.4
17
77.3
5
23.8
3
13.6 0.175
Stone composition Calcium Oxalate Calcium Phosphate Uric acid Cysteine Struvite
7 2 5 4 3
33.3 9.5 23.8 19 14.3
10 5 3 3 1
45.5 22.7 13.6 13.6 4.5
Stone free
15
71.4
21
95.5
0.046
Complications Clavien Class
2
9.5
9
40.9
0.018
Fever
Grade 1
2
9.5
4
18.2
Bleeding
Grade 2
0
0.0
3
13.6
Hydrothorax
Grade 3a
0
0.0
1
4.5
Ileum injury
Grade 3b
0
0.0
1
4.5
AC C
EP
TE D
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SC
RI PT
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Complete blood count
CT
Computed tomography
ESWL
Extracorporeal schock wave lithotripsy
FURS
Flexible ureteroscopy
IVP
Intravenous urography
KUB
Plain abdominal radiography
Mini-Perc
Miniaturized Percutaneous Nephrolithotomy
PCNL
Percutaneous Nephrolithotomy
RIRS
Retrograde intrarenal surgery
US
Ultrasonography
VCUG
Voiding Cyctourethrogram
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CBC
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LIST OF ABBREVIATIONS
S0022-5347(15)04328-1 10.1016/j.juro.2015.06.101 JURO 12751
To appear in: The Journal of Urology Accepted Date: 2 June 2015 Please cite this article as: Saad KSM, Youssif ME, Hamdy SAIN, Fahmy A, Hanno AGED, EL-Nahas AR, Percutaneous Nephrolithotomy (PCNL) Versus Retrograde Intra-renal Surgery (RIRS) in Treatment of Large Renal Stones (>2cm) In Pediatric Patients: A Randomized Controlled Trial, The Journal of Urology® (2015), doi: 10.1016/j.juro.2015.06.101. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
ACCEPTED MANUSCRIPT
Percutaneous Nephrolithotomy (PCNL) Versus Retrograde Intra-renal Surgery (RIRS) in Treatment of Large Renal Stones (>2cm) In Pediatric Patients: A Randomized Controlled Trial 1
1
1
1
RI PT
Karim S.M. Saad , Mohamed Elsaid Youssif , Seif Al Islam Nafis 1
R. EL-Nahas
2
From
2
Urology Department, Alexandria Faculty of Medicine
M AN U
1
SC
Hamdy , Ahmed Fahmy , Ahmed Gamal El Din Hanno , and Ahmed
Urology Department, Urology and Nephrology Center, Mansoura University
Keywords: Percutaneous Neprolithotomy; Retrograde intrarenal surgery;
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Flexible ureteroscopy; Renal calculi; Stones; Pediatric; Children Word Count: 2027 (Introduction through conclusion) Corresponding author:
EP
Karim S.M. Saad
Lecturer of Urology
AC C
Urology Department
Faculty of Medicine, Alexandria University Address: 25 Victor Emanuel square, Smouha, Alexandria, Egypt Tel: +201227887221 Email: [email protected]
ACCEPTED MANUSCRIPT
ABSTRACT Purpose: To compare the outcomes of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in treatment of children with >2 cm renal calculi. Patients and Methods: Between May 2011 and February 2014, 38 pediatric patients
RI PT
(<16 year-old) with renal calculi > 2cm were randomized between PCNL and RIRS. Demographic data, stone criteria, operative technique, radiation time, complications, blood transfusion, hemoglobin drop, stone free rates and hospital stay were compared between both groups. Stone free was document if there were no residual stones after
SC
one month.
Results: The study included 43 renal units; 21 units in RIRS group and 22 units in
M AN U
PCNL group. Operative time was comparable for both groups. The mean radiation time and hospital stay were longer after PCNL (P<0.001). The stone free rate of RIRS monotherapy was significantly lower than PCNL monotherapy (71% vs 95.5%, P=0.046). Patients in PCNL group had a statistically significant more complication rate compared with RIRS group (P=0.018). Three patients in the PCNL group received blood transfusions, whereas none of the children in the RIRS group needed
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blood transfusion (P=0.015).
Conclusion: For treatment of large or complex renal stones in pediatric patients, PCNL monotherapy had the advantage of better stone free rate while RIRS had the
AC C
EP
advantages of lesser radiation exposure, complications and hospital stay.
2
ACCEPTED MANUSCRIPT
INTRODUCTION Urolithiasis in pediatric patients has greater incidence in third world nations than developed countries due to malnutrition, metabolic abnormalities, environmental or dietary factors
(1,2)
. Historically, large and staghorn stones in children have been
treated with open procedures with considerable morbidity and lengthy convalescence.
RI PT
Surgical management of urolithiasis in children has evolved dramatically after the advent of shock wave lithotripsy (SWL) and it is currently the procedure of choice in treating most small upper tract calculi in children (3). Certainly, this offers tremendous advantages over open stone procedures, especially for small stones. However, not all
SC
stones are amenable to this treatment.
In the modern era of minimally invasive surgery, treatment of urolithiasis has
M AN U
been revolutionized with the advent of endoscopic techniques and improved technology (4). The introduction of percutaneous nephrolithotomy (PCNL) offered a new approach for these difficult stones. Major concerns regarding PCNL in children have been the size of the instruments in relation to patient size, blood loss, and mobile, smaller kidneys. It was reported that PCNL was efficacious, less invasive than open surgery, and it should be performed more often in the pediatric population .
TE D
(4, 5)
Following the advances in endoscopic instruments and development of smaller endoscopes and effective energy sources for stone disintegration, ureteroscopic management has become increasingly applicable in pediatric stone patients
(6)
.
EP
Although technological advances have resulted in ureteroscopic equipment that can be used in the urinary tract of children, caution must be exercised. The margin for
AC C
error is small, and the urologic surgeon must be familiar with the equipment, ureteroscopic techniques, and their limitations. The long-term consequences of ureteral endoscopic manipulations in the pediatric population remain undefined. Debate continues regarding the most efficacious modality for large renal
calculi in children. This study was conducted to compare the outcomes of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in treatment of children with >2 cm renal calculi.
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PATIENTS AND METHODS The study protocol was approved by the local ethical committee and it was conducted between May 2011 and February 2014 in urology department, Alexandria university hospital. Inclusion criteria were pediatric patients (<16 year-old) who have renal calculi larger than 2 cm. Exclusion criteria were uncorrected bleeding diathesis,
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renal insufficiency, congenital renal anomalies (such as horse shoe and ectopic kidneys) and contraindications to general anesthesia. The parents of included patients have signed an informed consent. Eligible patients were randomized using sealed closed envelopes between PCNL and RIRS.
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Preoperative workup:
All patients were evaluated with history taking, routine laboratory
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investigations; urinalysis, culture and sensitivity, complete blood count (CBC), coagulation profile and creatinine. Radiological evaluation included; plain abdominal radiography (KUB) and gray-scale ultrasonography (US). Non-contrast CT was performed for quantitative assessment of the stone burden and location. Technique of RIRS:
All procedures were done in lithotomy position under general anesthesia.
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Prophylactic antibiotics were administrated according to the child weight. Ureteroscopy was performed using 4.5 French (F) semirigid ureteroscope (Richard Wolf ®, Knittlingen, Germany). Then a second guidewire was introduced. A flexible ureteroscopy FlexX2 (Karl Storz Endoscopey, Tuttlingen, Germany) was through a
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ureteral access sheath (9.5-11.5 F) to minimize intrarenal pressure along the procedure. In cases of access sheath introduction failure, a JJ stent was left for passive
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dilatation of the ureter, and the patient was readmitted after 10 days for the procedure. Holmium: YAG laser was used for stone disintegration at energy of 0.4-0.6 Joules and pulse rate of 10-15 Hertz. Stones were fragmented into powder and smaller pieces without any trial for gravels removal. A 4.8F ureteral stent was left for 2-4 weeks after intervention. Technique of PCNL: All cases were done in prone position under general anesthesia. Contrast material was injected through a ureteric catheter for opacification of the collecting system. Renal puncture was performed under fluoroscopic guidance. Dilatation of the
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dictated by intraoperative events and according to each case individually. A nephrostomy tube was placed if there were intraoperative complications or there were significant residuals. A 4.8F ureteral stent was left for 2-4 weeks after intervention. Postoperative evaluation and follow-up:
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Stones retrieved at the end of the procedures were examined by infrared spectroscopy. KUB and ultrasonography were performed before discharge and after
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one month. Non-contract spiral CT was used in radiolucent stones. All ureteral stents were removed on outpatient bases. The stone free of each treatment as monotherapy was conferred by the absence of any stone fragments in follow up imaging. Statistical analysis:
Demographic data, stone criteria (number, length, and burden), operative technique, radiation exposure time, complications, blood transfusion, stone free rate
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and hospital stay were recorded and compared between both groups. Chi-square test was applied to compare categorical data. Mann-Whitney U test
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or t-test was used to compare continuous data as appropriate.
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RESULTS The study included 38 patients (43 renal units); 21 renal units in RIRS group and 22 renal units in PCNL group. Boys represented 66.7% of RIRS group and 63.6% in PCNL group (p=0.835). As shown in table 1, stones characters and operative time
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were comparable for both groups. The mean radiation time was longer in PCNL group (P<0.001) and hospital stay was also longer after PCNL (P<0.001).
Immediate conversion to PCNL was needed in 2 patients in RIRS group because the stones were not accessible with the ureteroscope (lower calyx stones).
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These 2 patients were included in RIRS group and considered as failure. A second session was needed in 2 patients (9.5%) in RIRS group and one patient (4.5%) in PCNL group. Follow-up was elected for 4 patients in RIRS group and one patient in
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PCNL group with small residual stones <4mm. The stone free rate of RIRS monotherapy was significantly lower than PCNL monotherapy (71% vs 95.5%, P=0.046). The efficiency quotient was 0.65 in RIRS and 0.95 in PCNL. Patients in PCNL group had a statistically significant more complication rate compared with RIRS group (P=0.018). Only 2 patients (9.5%) in RIRS group
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encountered pyrexia (<39oC). Fever was controlled by intravenous antibiotics and antipyretics. In PCNL group, 3 patients had intraoperative bleeding that required blood transfusion, one patient had ileum injury necessitated open repair and one patient with a supracostal puncture developed hydrothorax that was resolved
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spontaneously without chest tube placement. Modified Clavien classification of the complications is presented in table 1. Postoperative Hemoglobin drop was more in
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PCNL group (P=0.012).
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DISCUSSION The ultimate objective of stone therapy is to render the patient stone free. This is particularly crucial in the pediatric population that is by default considered high risk for recurrence. The importance of post-treatment stone-free status in children was demonstrated by Afshar et al who showed that 69% of the children with residual
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fragments ≤ 5 mm up to 48 months after SWL had symptomatic episodes or increase in stone size (7). This feature of pediatric stone disease should be factored in the choice of treatment modality.
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In children, RIRS lagged behind its use in adults owing to the initial unavailability of small instruments, coupled by the plethora in SWL in the 1980s. However, SWL was not the best choice in in stone burden ≥2 cm
(8)
The main
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drawback of SWL is that up to 75% of the patients would require multiple sessions (9). On the other hand, PCNL has a role in larger stone burden, complex and staghorn calculi, and after failed SWL
(10-12)
. The overall stone-free rate of our
pediatric series was 95.5% after PCNL procedure. These results are within the
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previously reported range of 67%-100%.
The Children’s Hospital of Philadelphia reported the largest case series utilizing flexible pediatric ureteroscopy
(6)
with RIRS used to manage 101 renal stones (87
lower polar). This study shows a success rate of 97% for calculi larger than 1 cm.
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However, it is noteworthy that access was not possible in the first surgery for 59% of the patients, raising concerns for additional anesthesia for more than half of their
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patients. The stone free rate in our patients was lower (71%), but the stone burden was considerably larger. Tanaka et al
(13)
reported their 5-year experience in pediatric
RIRS, Interestingly, initial stone-free status depended on pre-operative stone size (P=0.005). The younger patient age (P=0.04) and larger pre-operative stone size (P=0.002) influenced the need for extra procedures. The key result of the present study is that it showed lower stone free rates of RIRS versus PCNL for treatment of large, multiple and complex renal stones in children (P=0.046). However, PCNL remains more invasive with more incidence of complications than RIRS (41% versus 9.5%, P=0.018). Moreover, PCNL was associated with more severe complications. Bleeding was the most prominent
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ACCEPTED MANUSCRIPT complication in our series of PCNL as 3 out of the 22 patients had intraoperative bleeding (13.6%) that required blood transfusions. Zeren et al reported 24% incidence of hemorrhage requiring transfusion (10). On the other hand, no patients required blood transfusion in the RIRS group. Desai et al
(11)
reported 1.6 g/dl fall in hemoglobin
after PCNL. In the present study, mean hemoglobin deficit was significantly lower is
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RIRS group (1.6 versus 3.1gm/dl, P=0.012). The higher incidence of bleeding complications in the present study may be attributed to the size of tract dilatation (22F)
(14)
. We used this sheath size to allow extraction of larger stone fragments.
Recent series encourage the adoption of ultra-mini-perc and micro-perc for treatment
large and complex stone burden was not reported.
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of small renal stones in pediatric patients (15). However, the use of these techniques in
(16)
. In
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Chest complications are known after supracostal percutaneous access
current series seven patients needed a supracostal puncture for access to either a staghorn stone or stone located in upper calyx. One of them (14%) developed hydrothorax. In another series Anand et al reported that 13 patients required a supracostal puncture. Hydrothorax developed in one patient with supracostal puncture necessitating tube drainage
(17)
. Certain measures should be taken while performing
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supracostal punctures. First, the supra 11th rib approach is better to be avoided because of the higher incidence of pleural and pulmonary violation. The use of an Amplatz sheath, which should be well positioned, reduces the risk of symptomatic hydrothorax by allowing free exit of irrigant. Additionally, intra-operative chest
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fluoroscopy at the end of the procedure is beneficial to identify a fluid collection (16). Adjacent visceral injuries are another potential complication of percutaneous (18; 19)
. Early diagnosis is crucial for management and to decrease
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nephrolithotomy
morbidity for the patient. In current series, we reported one who encountered ileum injury (20).
No doubt, there is an increasing trend in the adoption of RIRS in the
management of renal stones in children. This has been facilitated by both the rapidly evolving technology and the particular drawbacks that are associated with SWL and PCNL. The initial concerns of increased risks and complications associated with ureteroscopic manipulation of the delicate ureteral orifices and ureters of children do not seem to be substantiated in the literature. However, a limited and a non-uniform
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ACCEPTED MANUSCRIPT reporting in the literature of the outcome of RIRS in children, making the surgeon's experience of principal importance in counseling and offering treatment to children with renal stones. Other advantages of RIRS in the present study are the shorter radiation exposure time and hospital stay. It is very important to reduce radiation exposure during
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treatment of calculi in children because they are susceptible to multiple recurrences and repeated treatments.
The main limitation of this study is the small sample size that may lead to type
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II statistical error. Therefore, the difference between stone free rates in the two groups did not reach statistical significance. However, including a sufficient number of pediatric patients with large renal calculi is difficult. Other randomized trials with
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larger number of patients are required.
CONCLUSION
For treatment of large or complex renal stones in pediatric patients, PCNL
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monotherapy had the advantage of better stone free rate while RIRS had the
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advantages of lesser radiation exposure, complications and hospital stay.
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References 1.
Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004; 15: 3225-31.
2.
Saxena A, Sharma RK. Nutritional aspect of nephrolithiasis. Indian J Urol.
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2010; 26: 523-30. 3.
Raza A, Turna B, Smith G, Moussa S, Tolley DA: Paediatric urolithiasis: 15 years of local experience with minimally invasive endourological management of paediatric calculi. J Urol 2005; 174:682–685.
Desai M: Endoscopic management of stones in children. Cur Opin Urol
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4.
2005; 15: 107-112. 5.
Kumar R, Anand A, Saxena V, Seth A, Dogra PN, Gupta NP: Safety and
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efficacy of PCNL for management of staghorn calculi in pediatric patients. J Pediatr Urol 2011; 7: 248-251. 6.
Kim SS, Kolon TF, Canter D, White M, Casale P. Pediatric flexible ureteroscopic
lithotripsy:
the
children’s
hospital
of
Philadelphia
experience. J Urol 2008; 180:2616-9
Afshar K, McLorie G, Papanikolaou F, et al.: Outcome of small residual
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7.
stone fragments following shock wave lithotripsy in children. J Urol 2004, 172:1600–3. 8.
Muslumanoglu AY, Tefekli A, Sarilar O, Binbay M, Altunrende F,
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Ozkuvanci U. Extracorporeal shock wave lithotripsy as first line treatment alternative for urinary tract stones in children: a large scale retrospective
9.
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analysis. J Urol. 2003; 170: 2405-8 Aksoy Y, Ozbey I, Atmaca AF, Polat O. Extracorporeal shock wave lithotripsy in children: experience using a mpl-9000 lithotriptor. World J Urol. 2004; 22: 115-9.
10.
Zeren S, Satar N, Bayazit Y, Bayazit AK, Payasli K, Ozkeçeli R. Percutaneous nephrolithotomy in the management of pediatric renal calculi. J Endourol. 2002; 16:75–8.
11.
Desai
MR,
Kukreja
RA,
Patel
SH,
Bapat
SD.
Percutaneous
nephrolithotomy for complex pediatric renal calculus disease. J Endourol. 2004; 18:23–7.
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Ozden E, Sahin A, Tan B, et al. Percutaneous renal surgery in children with complex stones. J Pediatr Urol. 2008; 4:295-298.
13.
Tanaka ST, Makari JH, Pope JC, 4th, Adams MC, Brock JW, 3rd, Thomas JC. Pediatric ureteroscopic management of intrarenal calculi. J Urol. 2008; 180: 2150–3. Yamaguchi A, Skolarikos A, Buchholz NP, et al; Clinical Research Office
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14.
Of The Endourological Society Percutaneous Nephrolithotomy Study Group: Operating times and bleeding complications in percutaneous nephrolithotomy: a comparison of tract dilation methods in 5,537 patients
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in the Clinical Research Office of the Endourological Society Percutaneous Nephrolithotomy Global Study. J Endourol 2011; 25: 933-9 15.
Ganpule AP1, Bhattu AS, Desai M. PCNL in the twenty-first century: role
16.
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of Microperc, Miniperc, and Ultraminiperc. World J Urol 2015; 33: 235-40 El-Nahas AR, Shokeir AA, El-Kenawy MR, Shoma AM, Eraky I, ElAssmyAM, Ghaly AM, El-Kappany HA. Safety and efficacy of supracostal percutaneous nephrolithotomy in pediatric patients. J Urol. 2008;180: 676-80
Anand A, Kumar R, Dogra PN, Seth A, Gupta NP. Safety and efficacy of a
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17.
superior calyceal puncture in pediatric percutaneous nephrolithotomy. J of Endourol 2010; 24: 1725-8. 18.
Bhageria A, Nayak B, Seth A, Dogra PN,
Kumar R. Pediatric
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percutaneous nephrolithotomy: Single-centre 10-year experience. J Ped Urol 2013: 9: 472-5.
Goger E, Guven S, Gurbuz R, Yilmaz K, Kilinc M, Ozturk A. Management of a
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19.
colon perforation during pediatric percutaneous nephrolithotomy. J Endourol. 2012; 26:1118-20.
20.
Saad KS, Hanno A, El-Nahas AR. Injury of the ileum during percutaneous nephrolithotomy in a pediatric patient. Can Urol Assoc J. 2014; 8: 204-6.
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Table 1: Comparison between the RIRS and PCNL for treatment of large renal stones (>2
RIRS (n=21)
PCNL (n=22)
Right
9 (42.9)
10 (45.5)
Left
12 (57.1)
12 (54.5)
6.44 (4.84)
6.93 (3.55)
5 (1.67-16.0)
8 (1.42-13.0)
Mean (SD)
79.5 (29.4)
69.8 (29.6)
Median (Range)
85 (30–135) 1.6 (0.8)
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1.5 (1.0–4.0)
3.0 (2.0 – 6.0)
0.53 (0.35)
1.60 (1.43)
0.45 (0–1.3)
1.40 (0.5-5)
1.1 (0.52)
2.59 (1.98)
1.0 (0.50–2.0)
2.0 (1.0–9.0)
P Value
Stone side 0.864
Mean (SD) Median (Range)
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Age (years)
Operative time (min)
Mean (SD) Median (Range) Hemoglobin Deficit (g/dl) Mean (SD) Median (Range) Mean (SD)
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Hospital stay (days) Median (Range)
No.
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Stone Burden Single Multiple Staghorn
3.1 (1.1)
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Radiation time (min)
70 (15–140)
%
No.
0.710
0.285
<0.001
0.012
<0.001
% 0.218
5
23.8
2
9.1
11
52.4
17
77.3
5
23.8
3
13.6 0.175
Stone composition Calcium Oxalate Calcium Phosphate Uric acid Cysteine Struvite
7 2 5 4 3
33.3 9.5 23.8 19 14.3
10 5 3 3 1
45.5 22.7 13.6 13.6 4.5
Stone free
15
71.4
21
95.5
0.046
Complications Clavien Class
2
9.5
9
40.9
0.018
Fever
Grade 1
2
9.5
4
18.2
Bleeding
Grade 2
0
0.0
3
13.6
Hydrothorax
Grade 3a
0
0.0
1
4.5
Ileum injury
Grade 3b
0
0.0
1
4.5
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Complete blood count
CT
Computed tomography
ESWL
Extracorporeal schock wave lithotripsy
FURS
Flexible ureteroscopy
IVP
Intravenous urography
KUB
Plain abdominal radiography
Mini-Perc
Miniaturized Percutaneous Nephrolithotomy
PCNL
Percutaneous Nephrolithotomy
RIRS
Retrograde intrarenal surgery
US
Ultrasonography
VCUG
Voiding Cyctourethrogram
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CBC
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LIST OF ABBREVIATIONS