Seventeen studies (10–19, 21, 22, 24–28) reported on incidence of stenosis after ureteroneocystostomy with a total of 7681 patients, and these studies were included for meta-analysis. The incidence of ureteral stenosis was significantly lower in the group of patients that received an extravesical anastomosis: relative risk (RR) of 0.67 (95% confidence interval [95% CI], 0.48–0.93; P=0.02) and I2 of 18% (Fig. 2). The percentage of stenosis was 3.13% and 3.51% for the group with an extravesical and an intravesical anastomosis, respectively. Some of these studies also reported on the location of the stenosis: at the ureterovesical junction (UVJ) (14, 19, 25, 26), the pyeloureterojunction (PUJ) (12, 14, 25, 26, 28), or (mid) ureteral (17, 25, 26). In these groups, there was no statistical difference. The RR for a stenosis was 0.63 (95% CI, 0.29–1.37; P=0.25) at the UVJ with I2 of 33%, 0.55 (95% CI, 0.15–2.08; P=0.38) at the PUJ with I2 of 43%, and 0.56 (95% CI, 0.20–1.58; P=0.27) for a (mid) ureteral stenosis with I2 of 0% when comparing intravesical with extravesical ureteroneocystostomy.
Urinary leakage was meta-analyzed in a total of 6410 patients from 16 studies (10–13, 15, 16, 18, 19, 21–28). The incidence of urinary leakage was significantly lower in the group of patients that underwent an extravesical anastomosis with a RR of 0.55 (95% CI, 0.39–0.80; P=0.001) and an I2 of 0% (Fig. 3). The percentage of leakage was 1.65% for the extravesical anastomosis and 3.25% for the intravesical anastomosis. A few studies pooled their data into UVJ leakage (14, 17, 23, 24, 26) and vesical leakage (23, 24). The difference in number of UVJ leakage was statistically significant with a RR of 0.47 (95% CI, 0.25–0.89; P=0.02) and an I2 of 0% in favor of the extravesical group, whereas vesical leakage did not show a statistically significant difference, with a RR of 0.13 (95% CI, 0.02–1.04; P=0.05) with I2 of 0%.
Total Number of Urinary Complications
Twelve studies (10–14, 17, 19, 20, 22, 25, 26, 28) reported on the total number of urologic complications in a total of 6366 patients and were included in our meta-analysis. The overall complication rate was significantly lower in the extravesical group with a RR of 0.56 (95% CI, 0.41–0.76; P<0.001) and an I2 of 44% (Fig. 4). In percentages, 5.41% of these complications were seen in the extravesical group and 8.61% in the intravesical group.
The incidence of hematuria after transplantation was described in five studies (11, 12, 14, 17, 25) with a total of 2159 patients. The meta-analysis showed significantly less frequent hematuria in the extravesical group with a RR of 0.41 (95% CI, 0.22–0.76; P=0.005) and an I2 of 0%. Hematuria occurred in 1.20% and 4% in the group of patients with an extravesical and an intravesical anastomosis, respectively.
Urinary Tract Infections
Three studies (564 patients) (11, 16, 27) reported on urinary tract infections. These data were used for meta-analysis and no statistical difference was found between the intravesical and the extravesical groups: RR of 1.00 (95% CI, 0.77–1.28; P=0.97) and I2 of 0%. Urinary tract infections were seen in 26.9% of the extravesical group and 28.25% of the intravesical group.
Despite a variety of urinary tract reconstruction techniques, postoperative urologic complications are the most frequent technical adverse event in kidney transplantation. These complications are frequently associated with substantial morbidity and generate excess costs caused by readmissions to the hospital, percutaneous (re)interventions, imaging, and surgical revisions of the ureteroneocystostomy (6).
The present systematic review and meta-analysis reveals an advantage of the extravesical anastomosis in kidney transplantation compared with the intravesical anastomosis. A statistically significant difference was found in stenosis, leakage, total number of urologic complications, and hematuria (Figs. 2–4), all in favor of the extravesical anastomosis. Regarding urinary tract infections, no significant difference was found between both types of anastomosis.
The majority of kidney transplant centers are performing an extravesical ureteroneocystostomy. However, no consensus exists in literature on the preferred technique. In 2010, a review of the literature on ureteroneocystostomy techniques in case of kidney transplantation was published by Kayler et al. (3). A historical and technical description of four surgical techniques was provided and analyzed, focusing on four specific urologic complications: urinary leakage, ureteric obstruction, hematuria, and symptomatic vesicoureteral reflux. Only two randomized controlled trials were performed and both showed a preference for the extravesical technique and the use of a prophylactic ureteric stent (21, 27).
Appointed benefits of the extravesical ureteral anastomosis are shorter operation time due to simplicity of the technique, a shorter ureteral length, and an additional reduced risk of ischemic injury to the distal ureter. Furthermore, the avoidance of a separate cystotomy with the additional risk of postoperative urinary leakage or ganglion injury (causing persistent neurogenic bladder dysfunction) is another advantage of an extravesical ureteroneocystostomy (3, 7).
Although this systematic review and meta-analysis provides important evidence for the technique of the ureteroneocystostomy in kidney transplantation, we must note some limitations of our study. The ureteroneocystostomy should provide a watertight, tension-free, and nonrefluxing anastomosis with good passage of urine production and without obstruction (16). Many modifications of the extravesical technique have been described, such as the use of running instead of interrupted sutures to create the ureteral mucosal anastomosis and tunneling by submucosal blunt dissection instead of muscular imbrications (3). All of these so-called modified techniques include extravesical access and an urothelial anastomosis. The use of these modified techniques may have biased the results of our meta-analysis. In addition, only Waltke et al. (27) describe a radiographic contrast injection before stent removal. None of the included studies describe whether a pyelography has been performed routinely or only on indication after clinical suspicion for early urologic complications. Inevitably, this must have influenced the rate of leakage or stenosis.
Likewise, the strong diversity in the use or no use of the different stent types (e.g., double-J or tube stenting) might have been an important confounder in our meta-analysis, because stenting may influence the healing of the anastomosis and thereby the total amount of urologic complications. Proponents of stent placement advocate relief of the anastomosis because of the postoperative presence of edema that may cause obstruction or leakage. The incidence of urinary tract infection was not increased in patients that receive a stent during kidney transplantation (21).
The studies included in our meta-analysis were performed in different eras of immunosuppressive medication; this might be another confounding factor. Other nontechnical risk factors for the development of urologic complications such as recipient age, number of renal arteries, and occurrence of acute rejection episodes (not scored prospectively or independently) may have interfered with our analysis. Furthermore, with the limited availability of prospective trials, selection bias may have occurred. For example, most of the described series included living and deceased donor grafts without having performed a multivariate analysis.
This systematic review and meta-analysis is the first step in providing a definite answer on superiority of either the extravesical or the intravesical technique, accounting for urologic complications and long-term outcome. To provide a superior level of evidence for either technique of ureteroneocystostomy, a sufficiently powered randomized controlled trial is recommended. Due to our systematic search, processing raw data, and computed RR, we managed to produce the best possible evidence. The results of our meta-analysis demonstrate superior results after extravesical anastomosis in kidney transplantation.
MATERIALS AND METHODS
All aspects of the PRISMA (29) statement were followed.
Literature Search Strategy
A systematic search of PubMed, Embase, and Cochrane Library was performed. Articles relevant to kidney transplantation and ureteroneocystostomy within the limits “human related” and “English language” were selected. The MeSH term “kidney transplantation” was used in PubMed. Other keywords used were “ureteroneocystostomy”, “Politano-Leadbetter”, “Lich-Gregoir”, “intravesical”, “extravesical”, “surgery”, and “anastomosis”. Manual reference checks of accepted papers in recent reviews and included papers were performed to supplement the electronic searches.
Studies were evaluated on relevance by two independent researchers (IKBS and KWJK) before inclusion. A random crosscheck was performed by a senior researcher (TT). Study selection was accomplished by three levels of screening (Fig. 1). At level 1, studies were excluded by title and abstract for the following reasons: case series, case reports, letters, editorials, comments, reporting on children, uretero-ureterostomy, two ureters, or kidney transplantation combined with pancreas transplantation. At level 2, the full text of studies accepted at level 1 was reviewed for relevance according to the same criteria. Specific attention was paid to a comparison between intravesical and extravesical anastomoses or double published data. Stent placement, primary transplantation or retransplantation, and living versus deceased donor did not interfere with our selection.
Data Extraction and Critical Appraisal
Data, design, and population were extracted from all included studies. Raw data on the amount of patients undergoing the different techniques had to be available for inclusion. Studies that included two different types of intravesical or extravesical anastomosis were excluded. The level of evidence of each study was scored using the Oxford Centre for Evidence-based Medicine Level of Evidence scale (30). The quality of each study was calculated using the Jadad score (31) for the randomized controlled trials and by the Newcastle-Ottawa Scale (32) for all cohort studies.
RRs (95% CIs) were calculated from raw data with the intravesical anastomoses group as reference. A meta-analysis was performed with urologic complications as outcome using Review Manager (RevMan) software (version 5.1.4; The Nordic Cochrane Centre, Copenhagen, Denmark). Each study was weighted by sample size, not by quality. Statistical heterogeneity was explored by inspecting the forest plot, testing the Q (heterogeneity χ2) and the I2 statistics. Summary estimators of treatment effects were calculated using a random-effects model with RR (95% CI). Overall effects were determined using the Z test. Endpoints were set on “stenosis”, “leakage”, “total number of urologic complications”, “hematuria”, and “urinary tract infection”. A subdivision was made for stenosis into UVJ stenosis and PUJ stenosis. Leakage was divided into UVJ leakage and vesical leakage. To assess publication bias, funnel plots were made.
Outline of Surgical Techniques
The Politano-Leadbetter anastomosis is created by performing a cystotomy on the anterior side to visualize the interior of the bladder and expose the trigone. A second cystotomy is performed to create a new ureteric orifice. The transplanted ureter is tunneled submucosally for approximately 2 cm. The distal site is trimmed and spatulated anteriorly at an optimal length to ensure a tension-free anastomosis. The distal ureter is sutured to the bladder mucosa with interrupted absorbable stitches. The cystotomy is closed in two layers to ensure a watertight anastomosis.
The Lich-Gregoir anastomosis is created by performing a cystotomy for 2 to 3 cm on the anterolateral surface of the bladder dome to expose mucosa of the bladder wall. A small incision is made in the mucosa. The transplanted ureter is trimmed and spatulated posteriorly. The mucosa of the bladder is sutured to the ureteral end with interrupted absorbable sutures. The detrusor muscle is closed over the anastomosis to create a submucosal tunnel with an antireflux mechanism.
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Keywords:© 2012 Lippincott Williams & Wilkins, Inc.
Kidney transplantation; Ureteroneocystostomy; Urologic complications