Minimally invasive percutaneous nephrolithotomy improves stone-free rates for impacted proximal ureteral stones: A systematic review and meta-analysis
Minimally invasive percutaneous nephrolithotomy improves stone-free rates for impacted proximal ureteral stones: A systematic review and meta-analysis
Zi-Ming Gao 0 1
Shan Gao 1
Hong-Chen Qu 1
Kai Li 1
Ning Li 0 1
Chun-Lai Liu 0 1
Xing- Wang Zhu 0 1
Yi-Li Liu 0 1
Ping Wang 0 1
Xiao-Hua Zheng 1
0 Department of Urological Surgery, Fourth Affiliated Hospital of China Medical University , Shenyang, Liaoning , P.R. China , 2 Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University , Shenyang, Liaoning , P.R. China , 3 Department of Urological Surgery, Liaoning Cancer Hospital/ China Medical University Cancer Hospital , Shenyang, Liaoning , P.R. China , 4 Department of Oncology Surgery, First Affiliated Hospital of China Medical University , Shenyang, Liaoning , P.R. China , 5 Department of Cardre Ward, No. 202 Hospital of People's Liberation Army , Shenyang, Liaoning , P.R. China
1 Editor: Shian-Ying Sung, Taipei Medical University , TAIWAN
We collected studies using PubMed, Embase, and Cochrane Library from 1978 to Novem-
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
Funding: This project was supported by grants
from the National Natural Science Foundation of
China (31271238) and the Science and Technology
Planning Project of Liaoning Province
(2013225089). The funders had no role in study
design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Urinary stones are common medical disorders and the treatment of impacted proximal ureteral stones (IPUS) is still a challenge for urologists. The aim of this study was to compare the efficacy and safety of minimally invasive percutaneous nephrolithotomy (MI-PCNL) and ureteroscopic lithotripsy (URL) in the treatment of IPUS via a meta-analysis.
ber 2016 and analyzed them using Stata 12.0 and RevMan 5.3. Odds ratios (ORs) and
standard mean difference (SMD) were calculated for binary and continuous variables
respectively, accompanied with 95% confidence intervals (CIs). All study procedures
followed the PRISMA guidelines.
Five prospective studies were included in our meta-analysis, with 242 MI-PCNL and 256
URL cases. MI-PCNL was associated with a longer postoperative hospital stay than URL
(SMD, 3.14; 95% CI, 1.27 to 5.55). However, no significant difference was observed in
operative time (SMD, -0.38; 95% CI, -3.15 to 2.38). In addition, MI-PCNL had higher initial (OR,
11.12; 95% CI, 5.56 to 22.24) and overall stone-free rates (OR, 8.70; 95% CI, 3.23 to 23.45)
than URL, along with lower possibilities of surgical conversion (OR, 0.11; 95% CI, 0.03 to
0.49) and postoperative shock wave lithotripsy (OR, 0.06; 95% CI, 0.02 to 0.18). Regarding
Competing Interests: The authors have declared
that no competing interests exist.
complications, no significant differences were observed between MI-PCNL and URL (OR,
1.39; 95% CI, 0.93 to 2.10), except for hematuria (OR, 4.80; 95% CI, 1.45 to 15.94).
MI-PCNL is optimal and should be considered as the preferred treatment method for IPUS, as it has better efficacy and a safety profile similar to that of URL. However, further high quality studies with larger sample size are required in future.
Urinary stones are frequently occurring medical disorders worldwide and their incidence has
been increasing in recent years.[
] Most of them are upper urinary stones (UUS), including
ureteral and renal stones. In the last decade, extracorporeal shock wave lithotripsy (ESWL),
ureteroscopic lithotripsy (URL) and percutaneous nephrolithotomy (PCNL) have emerged as
common surgical treatment options for UUS, while open surgery is only needed in a few rare
] With advancements in technology, new methods such as, flexible URL,
minimally invasive PCNL (MI-PCNL) and laparoscopic ureterolithotomy, have provided more
treatment choices to urologists. Within these, MI-PCNL (12-20F) has the advantages of
reduced hemorrhage, postoperative pain and hospital stays than traditional PCNL, and has
been recommended by many urologists.[
Impacted proximal ureteral stones (IPUS) are defined as ureteral stones fixed above the
level of fourth lumbar vertebra for at least 1 month.[
] Long-term IPUS may result in
hydronephrosis and even renal insufficiency of the affected side. Thus, it is necessary to find a suitable
management protocol for relieving obstruction and removing stones simultaneously. ESWL
has proven to be less efficient than URL in the treatment of renal and proximal ureteral stones,
particularly for critical renal insufficiency.[6±8] With respect to invasiveness, laparoscopic
ureterolithotomy still remains as a second-line and remedial measure for other operations.[
Thus, URL and PCNL are relatively optional methods for the treatment of IPUS. Of which,
MI-PCNL might be more suitable for the ureteral stones whose diameter is usually less than 2
cm. In the present study, we aimed to review the comparison in efficacy and safety between
URL and MI-PCNL for treatment of IPUS using meta-analysis.
Materials and methods
Literature searches and study selection
We searched published articles at PubMed, Embase, and Cochrane Library from 1978 to
November 2016. The search terms included ªNephrostomy, Percutaneous OR Minimally
Invasive Surgical Procedures OR percutaneous nephrolithot OR antegrade ureterolithotripsyº
and ªUreteroscopy OR ureterolithotripsy OR ureteroscopic lithotripsy OR retrograde
ureterolithotripsyº and ªUreteral Calculi OR [impacted (proximal OR upper) ureteral (stone OR
calcul )]º. Language and sample size were not restricted and the length of follow-up was at
least 3 months. In addition, to ensure that we reviewed the literature completely, we tried to
find full-text articles of the relevant abstracts and searched for potentially relevant studies from
the references of eligible articles. Two reviewers screened the results independently according
to the above selection criteria.
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Inclusion and exclusion criteria
The inclusion criteria were as follows: (1) the ureteral stones were diagnosed clearly and
impacted at the proximal ureter for at least 1 month; (2) studies that involved the comparison
between MI-PCNL and URL; (3) randomized controlled trials (RCTs), cohort studies or other
high-quality studies; (4) A follow-up of at least 3 months. Studies were excluded if there were
duplications or if they lacked essential data. In addition, letters, comments, reviews, abstracts,
or editorial articles were also excluded.
Data extraction and quality assessment
We extracted the characteristic data from studies using piloted forms, including first author,
year of publication, country, median age, sizes of the study population, proportion of male
subjects and the stone size. Primary outcomes were initial stone-free rate (SFR; 3±7 days after
operation), overall SFR (1±3 months after operation), operation time, and postoperative
hospital stay. The secondary outcomes included retreatment and auxiliary procedures (surgical
conversion and postoperative ESWL), total cost, and postoperative complications. For analysis
of bias risks, Cochrane tools were used for estimating RCT studies, including (1) adequate
sequence generation; (2) allocation concealment; (3) blinding; (4) incomplete outcome data
addressed; (5) free of selective reporting; (6) free of other bias. The Newcastle-Ottawa Quality
Assessment Scale (NOS) was used for cohort or case-control studies, which estimates selection,
comparability, and exposure.
We quantitatively compared the primary and secondary outcomes in our meta-analysis. Odds
ratios (ORs) with 95% confidence intervals (CIs) were calculated and compared for binary
outcomes between MI-PCNL and URL. For continuous variables, results were presented as
differences in the mean values between treatments with standard mean difference (SMD) and 95%
CIs. Heterogeneity between studies was assessed using the Q test and I2; with P<0.1 and
I2>50%, respectively, considered as significant heterogeneity. Subsequently, the
randomeffects model was used for analysis. For other analysis, we used the fixed-effects model. If
necessary, sensitivity or subgroup analysis was performed to analyze and eliminate the sources of
heterogeneity. Publication bias was assessed via construction of a funnel plot of operative time,
postoperative hospital stay, overall SFR, and total complications. All the above analyses were
performed using Stata 12.0 and RevMan 5.3. The P value was calculated as two-sided, and
P<0.05 was considered statistically significant.
All procedures followed the PRISMA guidelines (S1 Table); the search and selection process is
presented in Fig 1. A total of four RCTs and one non-randomized concurrent controlled trial
(Non-R) studies were included in our meta-analysis, with 242 MI-PCNL and 256 URL cases.
[5, 10±13] In the URL group, 183 patients underwent surgery with a rigid ureteroscope
(R-URL), while the other 73 patients received treatment with the flexible ureteroscope
(F-URL). The original characteristics and data from the selected publications are listed in
Table 1, and the quality evaluation is presented in the supporting information. Forest plots of
the meta-analysis on efficacy and safety are presented in Figs 2±4. In addition, our analysis had
no significant publication bias.
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Fig 1. The flowchart showing study search and selection process.
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Size of ®stulas
Operation time. All five studies were included in the forest plot (Fig 2A). Heterogeneity
analysis showed I2 = 99% and P = 0.000<0.05. Random-effect meta-analysis was applied
because of the severe heterogeneity. There was no significant difference in operation time
between the two groups (SMD, -0.38; 95% CI, -3.15 to 2.38).
Postoperative hospital stay. Four studies were included in the forest plot (Fig 2B). The
results of heterogeneity analysis were I2 = 98% and P = 0.000<0.05, which was severe; thus,
random-effect analysis was applied, which showed that MI-PCNL may be associated with a
longer postoperative hospital stay than URL (SMD, 3.14; 95% CI, 1.27 to 5.55).
SFR. Four studies were included in the forest plot of initial SFR (Fig 2C). Heterogeneity
analysis showed I2 = 0.0%, and P = 0.76>0.05. The fixed-effects model of meta-analysis was
performed, which showed that MI-PCNL has a higher initial SFR compared to URL (OR,
11.12; 95% CI, 5.56 to 22.24). In terms of overall SFR, all five studies were included in the forest
plot (Fig 2D). Heterogeneity analysis showed I2 = 0.0% and P = 0.76>0.05. There was no
heterogeneity, and the fixed-effects model showed that MI-PCNL also has higher overall SFR
compared to URL (OR, 8.70; 95% CI, 3.23 to 23.45).
Retreatment and auxiliary procedures. Three studies were included in the forest plot of
surgical conversion (Fig 3A). Heterogeneity analysis revealed I2 = 0.0% and P = 0.458>0.05.
No heterogeneity existed and the fixed-effect model of meta-analysis was performed, which
showed that MI-PCNL has a lower risk of surgical conversion compared to URL (OR, 0.11;
95% CI, 0.03 to 0.49). In addition, three studies were included in the forest plot of
postoperative ESWL (Fig 3B). There was also no heterogeneity between these studies (I2 = 0.0%,
P = 0.37>0.05), and the fixed-effect model showed that postoperative ESWL was more
common in URL compared to MI-PCNL (OR, 0.06; 95% CI, 0.02 to 0.18).
Cost. Apart from efficacy and safety, cost is an important concern for patients. In our
analysis, only one study reported the cost comparison between MI-PCNL and URL, which
revealed that the cost of MI-PCNL was higher than URL (SMD, 3.69; 95% CI, 3.21 to 4.17).
Postoperative complications. Grade IV Clavien system complications were rare in both
methods. The comparison on pain (OR, 1.42; 95% CI, 0.51 to 3.96), fever (I2 = 77%, P = 0.004;
OR, 1.23; 95% CI, 0.68 to 2.23), hematuria (OR, 4.80; 95% CI, 1.45 to 15.94), perforation
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Fig 2. Forest plot of primary outcomes between MI-PCNL and URL. Operative time (A), hospital time (B), initial SFR (C), and overall
(I2 = 0.0%, P = 1.00; OR, 0.33; 95% CI, 0.05 to 2.12), stricture (I2 = 0.0%, P = 0.64; OR, 0.32;
95% CI, 0.05 to 2.10), and hemoglobin decrease (I2 = 0.0%, P = 0.98; OR, 4.22; 95% CI, 0.68 to
26.17) were analyzed in our forest plot (Fig 3C), which showed that there were no significant
differences between MI-PCNL and URL, except for hematuria. In addition, the total incidence
rates of complications in MI-PCNL and URL were also similar (I2 = 45%, P = 0.04; OR, 1.39;
95% CI, 0.93 to 2.10).
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Fig 3. Forest plot of secondary outcomes between MI-PCNL and URL. Surgical conversion (A),
postoperative ESWL (B), and complications (C).
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Fig 4. Funnel plot evaluating the publication bias of studies. Hospital Stay (A), operation time (B), overall SFR (C), and complications
Risk of bias
A quality review of included studies was performed by Cochrane tools or NOS, and most
studies had a low risk of bias (S1 Fig, S2 Table). For all four RCT studies, no bias but blinding was
significant. The NOS score of the cohort study was eight, which suggested that it described
Analysis of publication bias was performed with a funnel plot of part outcomes, which showed
that no publication bias existed in our analysis (Fig 4). However, considering the small number
of included studies, we could not ensure its accuracy.
Recently, the incidence of urinary stones has increased significantly due to changes in people's
diets and lifestyle. Among different urinary stones, IPUS is a special type which indicates
longterm retention of stones at the proximal ureter. Urination is always difficult for IPUS patients
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and if not treated in time, renal failure and other life-threatening diseases might occur.
Ureteral polyp is the major cause of IPUS and it always needs to be treated at the same time.
Recently, PCNL and URL have emerged as the two common methods used for treatment of
IPUS. However, there are advantages and disadvantages of both procedures, and which
procedure is optimal for IPUS remains unclear and challenging for urologists.
URL could be performed as a routine method through natural tracts for treating distal
ureteral and bilateral stones effectively. In addition, the application of F-URL could reduce
invasiveness of the ureteroscope to some extent and has been used for small renal stones.[
However, URL has its natural defects. When treated by URL, stones, especially the proximal
ones, can easily move back to the renal pelvis. For example, Chow et al reported that about
25% patients who underwent URL suffered from complications of stone migration. Moreover,
if the patients' ureters are constrictive or anfractuous, it is difficult for the ureteroscope to
insert and reach stones. In recent years, the technology of PCNL has matured and can avoid
these disadvantages of URL. In addition, urologists can use most lithotripters through the
PCN tunnel and even treat the associated renal stones simultaneously. However, postoperative
pain and hemorrhage are still common complications for all types of PCNL. Thus, MI-PCNL
with a smaller size of percutaneous tract and less trauma, has already been popular in treating
renal and proximal ureteral stones.
Most conclusions of our analysis were similar to other empirical literature.[15±17] In our
study, no significant difference was observed in operative time, but MI-PCNL might require
longer postoperative hospital stays than URL. In terms of efficacy, MI-PCNL had higher initial
and overall SFRs, along with lower risk of surgical conversion and postoperative SWL than
URL, which reflected the higher operative success rate of MI-PCNL. With respect to safety, no
significant differences were observed in the comparison of total complications between the
two methods. Essentially, only hematuria was more common in MI-PCNL than URL. Notably,
perforation, stricture and infectious shock only existed in the URL group. Within all five
studies, there were three patients with perforation, four with stricture and one with infectious
shock among the 256 URL cases. In addition, severe hemorrhage, which is a common
complication of PCNL, only occurred in the MI-PCNL group. A total of three MI-PCNL cases needed
blood transfusion, and one of them underwent arterial embolization. Thus, we propose that
higher Clavien grade complications may be more common in URL than in MI-PCNL, and
urologists should always avoid these complications despite improvements in technology.
Moreover, Mehmet et al have reported that kidney damage from PCNL tracts was negligible
using radionuclide renography.[
] In conclusion, we present that MI-PCNL is more effective
and safe for treating IPUS than URL (irrespective of R-URL or F-URL), and should be the
preferred treatment method.
To minimize the occurrences of part complications, we also searched related literature. Liu
et al suggested that tubeless PCNL could reduce postoperative pain significantly.[
respect to fever, perioperative administration of anti-inflammatory drugs is necessary to
reduce the risk of infection and infective shock. Furthermore, Hamamoto et al. reported that a
combined surgery with MI-PCNL and URL was better than monotherapy, which is worth
paying attention to.[
Heterogeneity is an important component of meta-analysis. In the primary outcomes of
this study, high heterogeneity (I2>75) was present only in the comparison of operative time
and hospital stay. Differences in surgical skills and treatment concepts were the main reasons
for heterogeneity. Undeniably, operative levels remain uneven in different regions of the
world because of economic factors, which would directly affect operative time. In addition,
clinicians have different standards in the treatment of diseases, with certain urologists prolonging
postoperative hospital stay to ensure that the patients are well before they leave. However,
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others advocate day-operation, leaving patients with shorter hospital stay. In addition, the
heterogeneity of postoperative fever analysis was high, but considering the few included studies,
we did not perform sensitivity or subgroup analysis.
Our study is the first meta-analysis to compare MI-PCNL and URL for treating IPUS.
MI-PCNL is an emerging urological technology that is rarely used for the treatment of IPUS at
present. Thus, the results of our study could provide a new, effective, and safe choice for
surgeons in the treatment of IPUS. In addition, we only included five prospective studies with low
heterogeneity, which ensure the reliability of our results.
However, our study has a few limitations. First, the small number of studies included might
reduce the persuasiveness of conclusions. For example, only two or three studies were included
in the comparison of pain, stricture, and blood transfusion. Therefore, it is worth further
examining these parameters using large cohorts and studies. Second, almost all the studies that
compared the surgical methods did not have a double-blind design because of clinical
requirement, which reduces the quality of studies included. Third, all populations in our analysis were
Chinese, which limits the wide applicability of our results.
MI-PCNL has better efficacy and similar safety compared to URL. Thus, MI-PCNL is the
optimal method among these two for treatment of IPUS. However, studies with larger sample size
and detailed records are needed to further validate our results.
S1 Fig. Quality review of Cochrane tools.
S1 Table. PRISMA 2009 Checklist.
S2 Table. Quality review of NOS.
S3 Table. Search strategies.
S4 Table. The data of all studies.
Conceptualization: PW KL SG.
Data curation: XHZ YLL KL.
Formal analysis: ZMG SG.
Funding acquisition: XHZ PW.
Investigation: ZMG CLL.
Methodology: ZMG SG HCQ.
Project administration: XHZ PW.
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Software: ZMG SG.
Supervision: XHZ KL.
Validation: KL XHZ.
Visualization: XWZ NL.
Writing ± original draft: ZMG SG.
Writing ± review & editing: XHZ PW KL.
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nephrolithotomy overcomes the disadvantageous of percutaneous nephrolithotomy monotherapy.
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