Ureteral Wall Thickness Is an Effective Predictor of Ureteral Stone Impaction and Management Outcomes: A Systematic Review and Meta-analysis
2023; Lippincott Williams & Wilkins; Volume: 210; Issue: 3 Linguagem: Inglês
10.1097/ju.0000000000003561
ISSN1527-3792
AutoresNicholas Dean, Braden Millan, Michael Uy, Patrick Albers, Sandy Campbell, Amy E. Krambeck, Shubha De,
Tópico(s)Pediatric Urology and Nephrology Studies
ResumoYou have accessJournal of UrologyReview Articles1 Sep 2023Ureteral Wall Thickness Is an Effective Predictor of Ureteral Stone Impaction and Management Outcomes: A Systematic Review and Meta-analysis Nicholas S. Dean, Braden Millan, Michael Uy, Patrick Albers, Sandra M. Campbell, Amy E. Krambeck, and Shubha De Nicholas S. DeanNicholas S. Dean *Correspondence: Department of Urology, Northwestern University, 676 N St Clair, Suite 2300, Chicago, IL 60611 telephone: 312-926-5564; E-mail Address: [email protected] https://orcid.org/0000-0002-2202-3532 Division of Urology, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada Department of Urology, Northwestern University, Chicago, Illinois , Braden MillanBraden Millan Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada , Michael UyMichael Uy Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada , Patrick AlbersPatrick Albers Division of Urology, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada , Sandra M. CampbellSandra M. Campbell John W. Scott Health Sciences Library, University of Alberta, Edmonton, Alberta, Canada , Amy E. KrambeckAmy E. Krambeck Department of Urology, Northwestern University, Chicago, Illinois , and Shubha DeShubha De Division of Urology, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada View All Author Informationhttps://doi.org/10.1097/JU.0000000000003561AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: Ureteral stone impaction is associated with unfavorable endourological outcomes; however, reliable predictors of stone impaction are limited. We aimed to assess the performance of ureteral wall thickness on noncontrast computed tomography as a predictor of ureteral stone impaction and failure rates of spontaneous stone passage, shock wave lithotripsy, and retrograde guidewire and stent passage. Materials and Methods: This study was completed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A search was conducted in April 2022 for all adult, human, and English language studies investigating ureteral wall thickness using PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, Proquest Dissertations & Theses Global, and SCOPUS. A systematic review and meta-analysis using random effects model was conducted. Risk of bias was assessed using the MINORS (Methodological Index for Non-randomized Studies) score. Results: Fourteen studies with a pooled population of 2,987 patients were included for quantitative analysis, and 34 studies were included in our qualitative review. Meta-analysis findings suggest that a thinner ureteral wall thickness is associated with more favorable subgroup stone outcomes. Thinner ureteral wall thickness suggests a lack of stone impaction and was associated with improved rates of spontaneous stone passage, successful retrograde guidewire and stent placement, and improved shock wave lithotripsy outcomes. Studies lack a standardized ureteral wall thickness measurement protocol. Conclusions: Ureteral wall thickness is a noninvasive measure that predicts ureteral stone impaction, and thin measurements are predictive of successful outcomes. Variability in measurement methods confirms that a standardized ureteral wall thickness protocol is needed, and the clinical utility of ureteral wall thickness is yet to be determined. The prevalence of nephrolithiasis in the U.S. is approximately 10%, making up 1% of emergency room visits.1,2 Patients passing a stone may be at risk of recurrent presentations to the emergency room for renal colic, febrile urinary tract infection, or renal function deterioration.3 Identifying patients with low rates of spontaneous passage (SP) is important not only for stone management, but also for patient safety and setting patient expectations. Stone location and size are factors commonly utilized by a urologist to predict the likelihood of SP.3 Impaction of a ureteral stone into the ureteral wall has also been predicted to reduce the likelihood of SP.4 Impaction has been defined during ureteroscopy as visual adherence of a calculus to the ureteral mucosa, or by the inability to pass a wire by the stone during procedures.5 Functionally, impaction has been assumed when a stone fails to progress distally on serial imaging, and has been associated with worsened outcomes during shock wave lithotripsy (SWL), ureteroscopy, and ureteral stent insertion.6,7 Therefore, identifying patients with impacted stones may allow urologists to avoid unnecessary delays in the treatment of patients with a low likelihood of SP and to appropriately counsel their patients on the expected management course after endourological intervention. Recently, Yoshida et al identified that preoperative variables including age, midureteric stone location, and ureteral wall thickness (UWT) were predictive of identifying impacted ureteral stones at the time of ureteroscopy on multivariate analysis.8 Other preoperative factors identified to have utility in predicting stone impaction at time of ureteroscopy include higher degrees of hydronephrosis and larger stone size.8,9 Pericalculus UWT measures on noncontrast computed tomography (NCCT) imaging has been recently cited as a predictor of both stone impaction and worse endourological procedural outcomes on multivariate analysis.8-10 Anatomical studies have identified a human ureter to have a cross-sectional UWT of 0.95-2.0 mm.11,12 The ureteric wall consists of approximately 10% epithelium, 30% lamina propria, and 60% muscularis.11 In cases of stone impaction, the ureteral mucosa adjacent to the stone becomes edematous and under histological assessment has been shown to display increased interstitial fibrosis and muscularis hypertrophy.13 In a study examining cadaveric models, researchers found that there was a significant increase in the UWT with increasing age.14 Sarica et al found a positive correlation between UWT and inflammatory serum markers including C-reactive protein and erythrocyte sedimentation rate in patients with impacted proximal obstructing ureteric calculi.15 Although studies examining pathophysiological deviations in UWT are limited, this retrospective study provides some evidence of an inflammatory pericalculus process in patients with impacted ureteral calculi that may be involved with increasing UWT on cross-sectional imaging. The first mention of UWT as a predictor of stone outcomes originated in 2013 by Park et al.16 Their group investigated the utility of UWT measurements to predict the outcomes of patients who had undergone SWL. Park's team described their method of measuring UWT as using "… maximum zoom in the anterior/posterior CT image showing the longest diameter of stone; the UWT adjacent to the stone was measured by same physician."16 Sahin et al were among the initial research groups to investigate UWT and its ability to predict SP of ureteric stones.17 However, the researchers did not specify any details of how their measurements were derived. In the same year, Sarica et al examined UWT and its association with successful SWL outcomes in a prospective cohort study.18 Within their publication they provided axial noncontrast 5-mm "stone protocol" CT figures demonstrating the use of the measuring tool used in imaging software at the area of "stone impaction." However, in this and their 2019 publication they did not elaborate how their measurements were extrapolated or provide practical instructions for clinicians to measure UWT.18,19 In 2019 Yoshida et al elaborated on their methods to extract UWT measurements from imaging, reporting that the "UWT was the point of greatest soft-tissue thickness (ureteral wall ± periureteral edema) around the circumference of the stone; this evaluation ranged from the top to the bottom of the stone."8 Within this retrospective study protocol to limit bias they were the first to blind a radiologist and a urologist to outcome data when extracting UWT measurements in a soft-tissue radiodensity window (width 350, level 50). Chandhoke et al's 2020 protocol deviated from prior methodology by creating a novel surrogate measure called P-CUT (pericalculus ureteric thickness).20 The pericalculus ureteral measurement was converted to a surface area to have a more accurate 3D representation of the stone and the adjacent ureteral wall. Chandhoke et al concluded that this thickness surrogate measure would better account for ureteric asymmetry. Yamashita et al also introduced novel UWT surrogates including maximal ureteric area and ureteral volume derived from semiautomated software (Aquarius Intuition Viewer).21 Since the popularization of UWT, Yoshida's method has emerged as the most utilized measurement method in published studies.21-25 Despite researcher movement toward a standardized method of measuring UWT on CT imaging, incongruity still exists in protocols when examining which team members are reading the images and extracting UWT measures (Figures 1 and 2). Published methods range from a single unblinded reviewer to multiple blinded radiologist reviewers for extraction of UWT measures.21-26 No study to date has examined the variability in UWT measurements between researchers based on the method used, the number of readers, blinding methods, or the level of medical training/specialization. Figure 1. Standardized ureteral wall thickness manual measurement strategy. HU indicates Hounsfield units; NCCT, noncontrast computed tomography. Figure 2. Standardized Albers method/modified Yoshida method for measuring ureteral wall thickness. To date, no group has interrogated the quality of evidence investigating UWT or performed a systematic review examining the utility of UWT as a measure to predict stone outcomes. We aim to review the performance of UWT on NCCT as a predictor of ureteral stone impaction and failure rates of spontaneous stone passage, shock wave lithotripsy, and retrograde guidewire and stent passage. MATERIALS AND METHODS Search Strategy A protocol of our systematic review was created according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses; Supplementary Appendix 1, https://www.jurology.com).27 Our research protocol was prepared a priori; however, it was not registered on PROSPERO (the protocol can be accessed upon request from the corresponding author). On April 12, 2022, a literature search was conducted in consultation with an expert medical librarian. Sources included PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, Proquest Dissertations & Theses Global, and SCOPUS. Animal only–studies were excluded. No search filters or limits were applied. We obtained all studies and abstracts relevant to our study through to April 2022. Detailed search strategies are included in our supplementary materials (Supplementary Appendix 2, https://www.jurology.com). The references of all included studies were also reviewed to identify further relevant studies. Inclusion and Exclusion Criteria The research question and inclusion/exclusion criteria were selected a priori. Studies examining UWT and its use to predict SP, stone impaction, ureteroscopy, SWL, and stent insertion outcomes were included. Only human studies and English-language studies were reviewed. Noncomparative studies were included but not utilized in the meta-analysis. Pediatric studies were excluded. Study Selection and Data Extraction Two researchers (ND and BM) screened studies independently and in duplicate using Covidence Systematic Review software.28 Any discrepancies at the title and abstract stage were resolved by consensus. Any discrepancies at the full-text review were resolved by discussion with a third reviewer (SD). References of included studies were then screened. Two reviewers (ND, BM) extracted data independently and in duplicate in an electronic database. Inconsistencies were reviewed by the senior author (SD). Data extracted are included within our Supplementary Figures (https://www.jurology.com); no assumptions were made regarding missing information (Supplementary Table 1, https://www.jurology.com). Assessment of Quality Studies were assessed for quality via the MINORS (Methodological Index for Non-randomized Studies) score. The scoring categories are given a rating from 0 to 2, with a maximum score of 24 for comparative studies and 16 for noncomparative studies. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology to rate quality of evidence and grading strength of recommendations was performed for all studies included in the meta-analysis. Statistical Analysis Meta-analysis was performed on Cochrane Review Manager 5.4 software. Continuous variables were expressed as a weighted mean difference (MD) with a 95% confidence interval (CI). Heterogeneity was analyzed using the Q statistic and Higgins' I2 statistic. A random-effects model was used for all meta-analyses. The value α was set at .05 for significance. Subgroups were created based on outcomes of studies: SP, SWL, and success of retrograde wire placement or stenting. All results were reported in the form of a forest plot. A leave-one-out sensitivity analysis was performed for heterogeneous meta-analyses, by iteratively removing 1 study at a time to ensure pooled effect estimates were not driven by a single study. A study was deemed biasing if it changed the direction of magnitude of effect, or changed the significance of an outcome, when removed from the analysis. To account for stone size as a confounding variable, the meta-analyses were conducted only for studies with mean stone size differences which were ≤1.5 mm between cohorts. This was a data-driven threshold in order to decrease the magnitude of discrepancy between groups, and was the maximum cutoffs before meta-analysis would not be able to be conducted due to study ineligibility (≤2 studies eligible). Finally, exploration of study heterogeneity was conducted with the following subgroups: region (continent) of publication, prospective vs retrospective study, and study quality (MINORS score <15 and ≥15). RESULTS Study Identification Our initial database search identified 175 abstracts and full texts. After inclusion and exclusion criteria were applied, a total of 33 studies were included (Figure 3). Figure 3. Preferred Reporting Items for Systematic Reviews and Meta-analyses diagram. Study Characteristics and Quality There were 14 articles included for quantitative analysis, including 11 retrospective cohort studies, and 3 prospective cohort studies.3,10,15,17,18,21-24,26,29-32 The majority of studies originated from Turkey (7/14 studies, 50%). Study populations and inclusion/exclusion criteria within subgroup comparisons (SP, stent or wire placement, SWL) were fairly homogeneous. The mean±SD MINORS score was 11±2.2 for noncomparative studies, suggesting fair quality methodology. CT Protocol We observed heterogeneity in the CT protocols of studies examining outcomes associated with UWT. Of the studies included in our meta-analysis, 6/14 (43%) provided no information on their CT imaging protocols, and the remaining 8/14 (57%) clearly state that an NCCT was used to extract UWT measurements. When specified, 1.25- to 5-mm slice thickness was commonly utilized. No study protocol clearly examined UWT with a low-dose or ultralow-dose CT scan protocol. Meta-analysis UWT Outcomes Medical Expulsive Therapy/Spontaneous Passage Of the studies included in the meta-analysis, 6 focused on the association between UWT and spontaneous stone passage, and 67% (4/6) reported the use of concurrent alpha blockers. Failure of SP was defined as persistence of a ureteral stone on imaging at 4 weeks after initial stone presentation in 4/6 (67%) of these studies. Only 1 of the studies (17%) employed the use of routine NCCT at 4 weeks postoperatively, while 3/6 (50%) studies utilized x-ray of kidney, ureter, and bladder, and US imaging with reflex NCCT if there were concerns for failed passage. Mean stone size was 5.3 mm. All the studies included measured UWT at the point of greatest soft-tissue thickness (ureteral wall ± periureteral edema) around the circumference of the stone. Pooled analysis of these studies included 1,249 patients with 54% (674/1,249) of these patients successfully passing their stone. Successful stone passage was significantly associated with a thinner UWT (MD = −1.38; 95% CI: −1.59, −1.18; P < .001; Figure 4). Figure 4. Forest plot. CI indicates confidence interval; df, degrees of freedom; IV, weighted mean difference; SD, standard deviation; UWT, ureteral wall thickness. Stone Impaction/Retrograde Wire Passage Of the studies included in the meta-analysis, 3 focused on the association between UWT and success of retrograde guidewire placement or 5F ureteral catheters in the setting of an obstructing ureteral stone. Two-thirds of the studies measured UWT according to the Yoshida method, which included measuring the point of greatest soft-tissue thickness (ureteral wall ± periureteral edema) at the maximum stone diameter.20 Pooled analysis of these studies included 458 patients with 294/458 (64%) of these patients having a successful retrograde guidewire or ureteral catheter placement. Successful passage of a glide wire or 5F open-ended catheter on the initial retrograde attempt was interpreted as no evidence of stone impaction by the researchers in these studies and was found to be significantly associated with a thinner UWT (MD = −1.49; 95% CI: −1.73, −1.25; P < .001; Figure 4). SWL Of the studies included in the meta-analysis, 6 focused on the association between UWT and success of SWL for obstructing ureteric calculi. Success was defined as stone-free status on NCCT scan imaging at 3 months after SWL in 67% (4/6) of studies included. Three of the 6 studies measured UWT according to the Yoshida method, which included measuring the point of greatest soft-tissue thickness (ureteral wall ± periureteral edema) at the maximum stone diameter.8 Mean stone size of the cohort was 10.2 mm. Pooled analysis of these studies included 1,280 patients with 75% (959/1,280) of these patients successfully passing their stone on follow-up imaging. Successful SWL was significantly associated with a thinner UWT (MD = −1.84; 95% CI: −2.63, −1.05; P < .001; Figure 4). Retrograde Stent Passage Only 1 study within our review focused on the ability to place a retrograde ureteric stent and therefore was excluded from the meta-analysis. Sarica et al defined stent passage success as the ability to pass a 4.8F internal diameter stent in a retrograde fashion.8,25 Sarica et al measured UWT according to the Yoshida method, which included measuring the point of greatest soft-tissue thickness (ureteral wall ± periureteral edema) at the maximum stone diameter. Patients who failed stent placement required subsequent nephrostomy tube decompression. This study included 227 patients with a mean stone diameter of 8.9 mm. Successful retrograde stent passage was significantly associated with a thinner UWT (MD = −1.80; 95% CI: −2.05, −1.55; P < .001). Optimal UWT was 3.35 mm with a sensitivity value of 86% and a specificity value of 93% on receiver operating curve. Overall Stone Outcomes Of all the studies included within this meta-analysis, irrespective of the outcome assessed, favorable stone outcomes were significantly associated with thinner UWT measurements (MD = −1.54; 95% CI: −1.72, −1.36; P < .001) in patients with obstructing ureteral calculi (Figure 4). Recommendation In patients with a ureteral calculus, UWT should be used an adjunct to other clinical and radiological findings as a predictor for spontaneous stone passage, stone impaction, passage of a wire or stent, or successful extracorporeal shock wave lithotripsy (ESWL) treatment (weak recommendation, low quality of evidence). Exploratory Analyses Of the studies with a mean stone size difference of ≤1.5 mm between cohorts, meta-analyses found similar findings for all subgroups including medical expulsive treatment success, retrograde passage of a stent, and ESWL success (respectively, MD = −1.35; 95% CI −1.63, 1.06, P < .001; MD = −1.60, 95% CI −1.79, −1.41, P < .001; and MD = −1.74, 95% CI −2.03, −1.45, P < .001; Supplementary Figure 1, https://www.jurology.com). Leave-one-out sensitivity did not find any sole biasing studies that, when removed, changed significance of an outcome, or changed the direction of magnitude of effect. Exploration of study heterogeneity did not find any other meaningful subgroups (region of publication, retrospective nature of study, or study quality), though removal of Guler et al29 in the ESWL subgroup did decrease heterogeneity from 97% to 87%, but had no major change in effect size (still P < .001). DISCUSSION Our study is the first systematic review and meta-analysis to evaluate UWT and its use in relation to nephrolithiasis outcomes in adult patients. The pooled results of this meta-analysis suggest that a thinner UWT is associated with favorable stone outcomes, including spontaneous stone passage rates and SWL outcomes. These findings align with the hypothesis that increased UWT is caused by an inflammatory process associated with impacted stones, which are known to have worse outcomes.33 Currently there is a paucity of studies examining UWT as a predictor of retrograde stent placement.25 Many of the studies within the systematic review provide optimal UWT cutoff measurements with associated sensitivity, specificity, and positive and negative predictive values from receiver operator curves to predict successful outcomes. Optimal UWT measures were included in 71% (10/14) studies ranging from 1.8 mm to 5.3 mm (mean 3.1 mm). We were unable to combine these within our meta-analysis to suggest a universal UWT cutoff for each subgroup analysis. At this point in time, the exact utility of how UWT can and should be utilized in an individual patient encounter is yet to be defined. Almost all studies reviewed included a single maximum UWT measure; however, 2 studies reported surrogate measures of ureteral thickness and 1 study used automated software to calculate their ureteral thickness surrogate. Studies examining the use of automated software will likely reduce the variability in ureteral thickness measurements, but until automation can be achieved widespread adoption will be limited. None of the studies reviewed reported the amount of time required to extract a UWT measure. This could be a potential barrier to the inclusion of this method in the clinical decision-making process. This systematic review used a comprehensive search, and we reviewed all available English abstracts and full texts examining UWT. Our meta-analysis is limited by the low number and low quality of studies currently available. Most studies incorporated were single center and had heterogeneity in their protocols for measuring UWT as discussed in our results. Furthermore, the findings of individual retrospective studies included may have been influenced by a confirmation bias of UWT reviewers who were not blinded to the patient's outcome. Within the meta-analysis, 9/14 (64%) had a protocol that reported that the CT reviewers were blinded to the outcome, and only 3 of the studies reported multiple independent duplicate reviewers. Of the studies 6/14 (43%) included a urologist UWT reviewer, 8/14 (57%) reported that a radiologist interpreted the CT images, and the remaining studies did not specify who was recording these measurements. Slight differences in inclusion criteria and more significant differences in the protocols for measuring UWT may also contribute to the moderate to high range of heterogeneity (i2=0.45-0.97) observed in the subgroup analysis (Figure 4). Finally, stone size is a confounding variable that could not be completely removed through this analysis. Though exploratory meta-analyses of papers with stone size differences ≤1.5 mm between groups did not highlight meaningful changes in our outcomes (Supplementary Figure 1, https://www.jurology.com), stone size was different in the majority of papers (9/14 papers that reported stone size). It would be prudent for future studies on UWT to control for stone size to determine if these 2 are truly confounding, rather than correlated. This review has highlighted gaps in the published literature and the need for further prospective studies utilizing UWT in key clinical situations. A standardized protocol for measuring UWT is required to minimize interstudy heterogeneity. It is currently unclear how UWTs, extracted by manual or automated techniques, are affected by the CT scan protocol (IV contrast, noncontrast, low-dose CT imaging, slice thickness, etc). CONCLUSIONS Thin measurements of UWT are predictive of favorable outcomes for patients with obstructing ureteral calculi. Variability in measurement methods confirms that a standardized UWT protocol for future studies is required. The exact utility of how UWT can and should be utilized in an individual patient encounter is yet to be determined by prospective cohort studies. REFERENCES 1. . Epidemiology and economics of nephrolithiasis. Investig Clin Urol. 2017; 58(5):299-306. Crossref, Medline, Google Scholar 2. Agency for Healthcare Research and Quality (US). Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. 2006. https://www.ncbi.nlm.nih.gov/books/NBK52651/ Google Scholar 3. . 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Radiological noninvasive assessment of ureteral stone impaction into the ureteric wall: a critical evaluation with objective radiological parameters. Investig Clin Urol. 2017; 58(5):339-345. Crossref, Medline, Google Scholar Support: None. Conflict of Interest: Dr Amy Krambeck is a consultant for Ambu, Boston Scientific, Karl Storz, Lumenis, Virtuoso Surgical, and Wolf. She is on the data safety monitoring board for Sonomotion. Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 210Issue 3September 2023Page: 430-437Supplementary Materials Peer Review Report Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.Keywordstomographyureteral calculiextracorporeal shockwave therapynephrolithiasisx-ray computedMetrics Author Information Nicholas S. Dean Division of Urology, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada Department of Urology, Northwestern University, Chicago, Illinois *Correspondence: Department of Urology, Northwestern University, 676 N St Clair, Suite 2300, Chicago, IL 60611 telephone: 312-926-5564; E-mail Address: [email protected] More articles by this author Braden Millan Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada More articles by this author Michael Uy Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada More articles by this author Patrick Albers Division of Urology, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada More articles by this author Sandra M. Campbell John W. Scott Health Sciences Library, University of Alberta, Edmonton, Alberta, Canada More articles by this author Amy E. Krambeck Department of Urology, Northwestern University, Chicago, Illinois More articles by this author Shubha De Division of Urology, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada More articles by this author Expand All Support: None. Conflict of Interest: Dr Amy Krambeck is a consultant for Ambu, Boston Scientific, Karl Storz, Lumenis, Virtuoso Surgical, and Wolf. She is on the data safety monitoring board for Sonomotion. Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed. Advertisement Advertisement PDF downloadLoading ...
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