A Nomogram to Predict Stricture-free Survival in Patients with Ureteral Stricture after Balloon Dilation

doi:10.21203/rs.3.rs-290900/v1

Download PDF

Research article

A Nomogram to Predict Stricture-free Survival in Patients with Ureteral Stricture after Balloon Dilation

https://doi.org/10.21203/rs.3.rs-290900/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Balloon dilation is a commonly used minimally invasive endourological treatment of ureteral stricture, but the postoperative recurrence rate is relatively high. And factors contributing to recurrence after treatment are poorly understood. Herein, we sought to develop a novel clinical nomogram to predict ureteral stricture-free survival in patients suffering from ureter stricture and performed balloon dilation.

Methods

The nomogram was established based on a retrospective analysis of 321 patients diagnosed with ureter strictures from January 2016 to January 2020 in Sun Yat-sen Memorial Hospital using the Cox regression model. Perioperative clinical data and disease outcomes were analyzed. Discrimination of the nomogram was assessed by the concordance index (C-index) and the calibration curve. The results were internally validated using bootstrap resampling.

Results

Overall, 321 patients with a median follow-up of 590 days were enrolled in the study, among which 97 patients (30.2%) developed recurrence of ureteral stricture during follow-up. Five variables remained significant predictors of ureteral re-stricture after multivariable analyses: stricture nature (P < 0.001), urinary nitrite (P = 0.041), CKD (P = 0.005), stent retention time (P < 0.001), and balloon size (P = 0.029). The calibration craves for the probability of 1-, 3-, and 5-years stricture-free survival (SFS) presented satisfied with the consistency of nomogram prediction and actual observation. The C-index of the model was 0.74 (95% CI 0.70–0.79).

Conclusions

Our study developed the first nomogram to effectively predict stricture-free survival in patients suffering from ureter stricture after balloon dilation. It is helpful to identify the optimal patients with ureter stricture for balloon dilation and improve treatment outcomes. However, further external validation of the nomogram is warranted.

Urology & Nephrology

Nomograms

prognosis

recurrence

Ureteral stricture

Balloon dilation

Ureteral stenosis is a well-known long-term complication that can impair kidney function, mainly caused by various factors, including benign or malignant.[1] Benign ureteral stricture occurred mainly after pelvic and abdominal surgery, ureteral injuries from lithiasis and endoscopic operation, infections, retroperitoneal fibrosis, renal transplantation, urinary diversion, endometriosis, neurogenic bladder disorder, and idiopathic causes.[2–4] Urothelial carcinoma, prostatic, ovarian, metastatic cervical, breast, and colorectal cancer are the primary causes of another type of ureteral stricture: malignant ureteral stenosis.[5] Although the gold-standard treatment for ureteral reconstructive operation is open surgery,[6] endourological procedures are often used as a first-line treatment.[7] The advantageous technique is considered a safe alternative to ureteral stricture. It postpones or even potentially shuns the needs of open or laparoscopic ureteral reimplantation.[8] Besides, many documents prove that endoscopic interventions are associated with less-invasive and cost-effective.[9]Endoscopic treatments commonly used for ureteral strictures include balloon dilation and endo-ureterectomy. Balloon dilation has been applied to treat patients with ureteral stenosis for nearly 100 years. However, little is known about the long-term results of patients undergoing balloon dilation. There is still no guidelines or consensus on balloon size, dilation duration, and postoperative double-J-stent retention time and number. According to available reports, success rates of ureteral strictures with balloon dilation vary between 33% and 100% amongst all populations.[10] Many factors may affect the success rates: aetiology, stricture location, stricture length, dilation duration, stent duration, stent number, perioperative renal function, infection. In this study, we analyzed these predictive factors for the recurrence of stricture after balloon dilation and the incidence of recurrence of stricture after dilation. We aimed to build a useful and practical nomogram for predicting the stricture recurrence of patients with ureteral stricture after ureter balloon dilation.

Patient and Study Design

We developed the nomogram from a patient cohort from Sun Yat-sen Memorial Hospital (Guangzhou, China). We utilized a retrospective cohort study of patients diagnosed with ureteral stricture from January 2016 to January 2020.

Patients fulfilling the following eligibility criteria were enrolled for analysis: (a) individuals diagnosed with ureteral strictures confirmed by imaging and ureteroscopy. The preoperative evaluation was similar in all patients, including ultrasound, renal scintigraphy, intravenous pyelography, antegrade pyelography, CT scan, and/or cystoureteroscopy. (b) All procedures must access technical success. Technical success has defined that the ureteroscope and guidewire can pass through the ureteral stricture after balloon dilated, and then successfully indwell the double J ureteral stent. (c) Patients undergoing endoscopic balloon dilation with the postoperatively indwelling ureteral stent. Patients were excluded from analysis if they had malignant tumours that were not cured or in remission or lost follow-up.

Data collection

The following demographic and clinical characteristics had extracted from medical records: age, gender, disease characteristics, dilated side, stenosis location, aetiology classification, degree of hydronephrosis, retention time and the number of stents, balloon size, dilation duration, stenosis length and diameter, perioperative urine leukocyte nitrite, urine culture, Scr, and so on. When processing the data, we converted part of continuous variables into categorical variables.

All participants underwent telephone follow-up and outpatient review. Follow-up data obtained from the patient's last outpatient review and contact include laboratory examinations, imaging checkups, and recorded urological symptoms available. Stricture-free had defined as a situation that the patient had a stable renal function, no urological symptoms, no evidence of worsening hydronephrosis, and no need for further treatment after the stent was removed. Patients' stricture-free survival (SFS) was from the day of withdrawing double-J-stent to the date of relapse or last contact. The overall follow-up time had defined as the interval from surgery to recurrence or the last contact. Our primary endpoint was the recurrence status of ureteral stricture and SFS time. Finally, we established a prediction model of SFS.

Statistical analysis

The primary endpoint was the onset of ureteral re-stricture after ureter balloon dilation. Log-rank test and Breslow test were used to find potentially independent prognostic variables. The missing baseline data were accounted for via multiple imputations, Cox regression analysis was used for multivariable analyses. The final model was determined by the forward LR step-down process that including all significant covariates from the univariate analysis. Statistical analysis to recognize independent prognostic factors was performed using SPSS version 25.0 for Windows (IBM Corporation, Armonk, New York, USA). On all tests, a p-value of <0.05 demonstrated have a significant statistical difference. A nomogram was then developed based on the final model using the survival, RMS, and foreign package in R (version 4.0.2, R Foundation for Statistical Computing, Vienna, Austria) (http://www.R-project.org) [11].

The performance of the nomogram had assessed by discrimination and calibration. The bias of the nomogram had measured by the bootstrap bias-corrected estimate of concordance index (C-index). [12-14] AUC was used to assess the specificity and sensitivity of the nomogram. And a bootstrapping-based calibration plot of the model had evaluated by comparing actual SFS probability with nomogram-predicted SFS probability.[15] We repeatedly fitted the nomogram to 2,000 bootstrap samples and assessed its performance on the original samples.[16]

Additional Table 1 lists the demographic and clinical characteristics. 327patients met the screening criteria of the current study. A total of 321 patients were included and analyzed due to 6 cases lost to follow-up. The ureteral stricture was most commonly secondary to ureteric lithiasis (55.96%), followed by gynaecological neoplasia surgery (11.01%) and urologic neoplasm (7.34%) (Figure.1A). 85.02% of the ureteral stricture were benign. According to aetiology, treatment results of the obstruction have presented in Figure.1B. During a median follow-up of 590 days, 97 of 321 patients (30.2%) developed ureteral restenosis (interquartile range (IQR) 335–1024 days). The median SFS was 406 days (IQR 93–852 days).

The overall ureteral re-stricture rate was 30.2%. Concerning etiological factors, we identified that patients who took radical cystectomy experienced the highest ureteral restenosis rate (63.1%), followed by intestinal tumours (50%). Table 1 showed the results of the univariable and multivariable Cox regression analyses used to forecast the likelihood of stricture recurrence upon dilation surgery. After applying a forward stepwise identification process, the best-simplified nomogram had developed. We found that stricture nature (P < 0.001), urinary nitrite (P = 0.041), CKD (P = 0.005), stent retention time (P < 0.001), and balloon size (P = 0.029) were independent risk factors for relapse of ureter stricture. Patients with malignant stricture, urinary nitrite positive, and CKD 5 were prone to ureteral restenosis, while patients with stent retention time < 3 months and dilation with F24 balloon had the highest ureteral patency rate.

The predictive nomogram that integrated all these significant predictors for 1-year, 3-year, and 5-year SFS was constructed and had depicted in Fig. 2. The nomogram had good predictive ability with a C-index of 0.74 (95% CI 0.70–0.79). Internal validation showed that the 1-, 3-, and 5-year SFS predictive accuracy of our nomogram (measured by AUC values) was 0.740, 0.768, and 0.752, respectively (Fig. 3A). Besides, a favourable consistency had shown between the predicted and actual 1-,3-, and 5-year SFS probability, which validated the accuracy of the model as demonstrated by Fig. 3B.

To our knowledge, this study is the first to develop and validate a predictive nomogram to identify patients at increased risk of ureteral restenosis after balloon dilation. The model incorporated five items that should be evaluated with priority in clinical practice, including narrow nature, balloon size, NIT, CKD, and stent retention time.

In our study, 97 patients relapsed during follow-up, with the overall ureteral re-stricture rate was 30.2%. The results are superior to a patency rate of 41.1% reported by Campschroer et al.[1 2] Similarly to Stehman, we observed that benign stenosis is more suitable for balloon dilation than malignant stenosis (recurrence rate:25.8%vs51.0%). [3 4] As was shown in Fig. 1, The lowest recurrence rate had seen in stenosis secondary to both ureteral polyps (14.2%) and vascular compression (14.2%), followed by secondary to lithiasis (25.9%) and surgery for benign gynecologic disease (27.7%). All of them belonged to benign stricture. The long-term patency rate of dilation for benign stenosis was comparable to that of open surgery, which indicated that balloon dilation could replace open surgery to treat benign ureteral strictures. However, 14.6% of patients failed immediately after the stent was withdrawing, and a new stent was required to be inserting. These patients were considered not suitable for balloon dilation unless not tolerate open surgery. 41.67% of the above patients belonged to malignant. Therefore, the best indication for balloon expansion is benign stenosis, such as surgery secondary to stones, ureteral polyps, vascular compression, and benign gynaecological diseases.

Some strictures (19 5.81%) were observed secondary to the laparoscopic radical cystectomy (LRC 12 3.67% recurrence rate:66.67%) or the robot-assisted radical cystectomy (RARC 7 2.14% recurrence rate:28.5%). These strictures were possibly secondary to ischemia in the context of a widespread incision.[5] It is worth noting that stenosis secondary to RARC has a lower recurrence rate after balloon dilation than other stenoses secondary to LRC.

In univariate analysis, no significant statistical difference had revealed among different stenosis sites or the number of stents retained. It is similar to previous studies that reported that there was no apparent association between stricture location (upper, mid, or distal ureter) with long-term success rate. [3 6–10] M.J.van Son's study reported that the stricture side was an independent risk factor for stricture recurrence (P = 0.009, HR 0.35, 95%CI 0.16–0.77).[1] However, there was no significant difference in SFS between patients with left ureter stricture and those with the right ureter stricture in our study (P = 0.504). Interestingly, our results found no significant difference in SFS between one and two stents retention (P = 0.293). Two stents retention might cause ureteral ischemia that leads to a bad outcome.

Stavros I. reported that when indwelling stents for prolonged periods, stents may prevent tissue repair for inflammation.[2] In our study, balloon sizes were associated independently with SFS, which is consistent with several previous studies showing that appropriate size could reduce the damage to the blood supply and rupture the fibrous tissue in the stenosis. [11 12]

CKD is also considered to be an independent risk factor for patients with stenosis recurrence after balloon dilation, which is consistent with previous studies that kidney function was considered an important predictor. [2 13] Moreover, our study showed a significant positive correlation between the five CKD stages.

Our study possesses several strengths. First, our nomogram had established through the analysis of a relatively large patients cohort. Furthermore, the calculation method of follow-up time used more accurately reflected the recurrence of stenosis. Also, the nomogram is easily applicable in clinical practice. Therefore, it can use as an essential screening tool that allows us to improve clinical care decisions for patients with a ureteral stricture. Surgeons and patients could make better choices through this usable rating tool before surgery. However, our research also has some limitations. First, the developed nomogram was based on data obtained retrospectively from a single centre. Second, due to missing data, some important factors such as the length and diameter of the stenosis were not included in this study. Although this model showed good predictive ability through internal validation, it still needs external validation.

Ureteral stricture

C-index

Concordance index

AUC

Area under the curve

SFS

Stricture-free survival

CKD

Chronic kidney disease

BMI

Body mass index

Scr

Serum creatinine

eGFR

Estimated glomerular filtration rate

Standard deviation

IQR

Interquartile range

Ethics approval and consent to participate:

This study uses data collected retrospectively as part of the SUN YAT-SEN Memorial Hospital’s database. Data collection and analysis plan were approved by the Institutional Ethics Committee of SUN YAT-SEN Memorial Hospital. All patients provided informed written consent for the procedure. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Availability of data and materials

The datasets analyzed during the current study available from the corresponding author on reasonable request.

Competing interests

None.

Funding

The study was funded by the Science and Technology Planning Project of Guangdong Province, China. (No.2017A020215072). The funder played no role in design of the study, collection, analysis, and interpretation of data or in writing the manuscript.

Authors’ Contributions

JTH, CL and MCG conceived and designed the study, participated in the collection of data and data analysis, and drafted the manuscript. JLH assisted in the design of this research and project development. KWL, WH, DJZ, WLX, HH , MJX, JH participated in the collection of data.

All authors read and approved the final manuscript.

Acknowledgments

We thank Dr Xiaoming Rong (Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) her contribution to English writing and statistics of the article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Duan H, Zhu W, Zhong W, Li X, Zeng G. Balloon dilation for failed pyeloplasty in children? Int Braz J Urol 2019;45(3):617-20 doi: 10.1590/S1677-5538.IBJU.2018.0407[published Online First: Epub Date]|.
Netto Junior NR, Ferreira U, Lemos GC, Claro JF. Endourological management of ureteral strictures. J Urol 1990;144(3):631-4 doi: 10.1016/s0022-5347(17)39541-1[published Online First: Epub Date]|.
Tyritzis SI, Wiklund NP. Ureteral strictures revisited...trying to see the light at the end of the tunnel: a comprehensive review. J Endourol 2015;29(2):124-36 doi: 10.1089/end.2014.0522[published Online First: Epub Date]|.
Richter F, Irwin RJ, Watson RA, Lang EK. Endourologic management of benign ureteral strictures with and without compromised vascular supply. Urology 2000;55(5):652-7 doi: 10.1016/s0090-4295(00)00484-2[published Online First: Epub Date]|.
Lau KO, Hia TN, Cheng C, Tay SK. Outcome of obstructive uropathy after pelvic irradiation in patients with carcinoma of the uterine cervix. Ann Acad Med Singap 1998;27(5):631-5
Varda BK, Johnson EK, Clark C, Chung BI, Nelson CP, Chang SL. National trends of perioperative outcomes and costs for open, laparoscopic and robotic pediatric pyeloplasty. J Urol 2014;191(4):1090-5 doi: 10.1016/j.juro.2013.10.077[published Online First: Epub Date]|.
Kaouk JH, Sagalovich D, Garisto J. Robot-assisted transvesical partial prostatectomy using a purpose-built single-port robotic system. BJU Int 2018;122(3):520-24 doi: 10.1111/bju.14194[published Online First: Epub Date]|.
van Son MJ, Lock M, Peters M, van de Putte EEF, Meijer RP. Treating benign ureteroenteric strictures: 27-year experience comparing endourological techniques with open surgical approach. World J Urol 2019;37(6):1217-23 doi: 10.1007/s00345-018-2475-4[published Online First: Epub Date]|.
Brooks JD, Kavoussi LR, Preminger GM, Schuessler WW, Moore RG. Comparison of open and endourologic approaches to the obstructed ureteropelvic junction. Urology 1995;46(6):791-5 doi: 10.1016/s0090-4295(99)80345-8[published Online First: Epub Date]|.
Lucas JW, Ghiraldi E, Ellis J, Friedlander JI. Endoscopic Management of Ureteral Strictures: an Update. Curr Urol Rep 2018;19(4):24 doi: 10.1007/s11934-018-0773-4[published Online First: Epub Date]|.
Jalaeian H, Talaie R, Hunter DW, Golzarian J, Rosenberg MS. Comparison of tandem ureteral stents, cryoplasty, and cutting balloon ureteroplasty in treatment of refractory transplant ureteral strictures. Clin Transplant 2020;34(6):e13859 doi: 10.1111/ctr.13859[published Online First: Epub Date]|.
Harrell FE, Jr., Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA 1982;247(18):2543-6
Liang W, Zhang L, Jiang G, et al. Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer. J Clin Oncol 2015;33(8):861-9 doi: 10.1200/JCO.2014.56.6661[published Online First: Epub Date]|.
Rose PG, Java J, Whitney CW, et al. Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy. J Clin Oncol 2015;33(19):2136-42 doi: 10.1200/JCO.2014.57.7122[published Online First: Epub Date]|.
Renfro LA, Goldberg RM, Grothey A, et al. Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en Cancérologie Digestive Database. J Clin Oncol 2017;35(17):1929-37 doi: 10.1200/jco.2016.71.5771[published Online First: Epub Date]|.
Serenari M, Han KH, Ravaioli F, et al. A nomogram based on liver stiffness predicts postoperative complications in patients with hepatocellular carcinoma. J Hepatol 2020;73(4):855-62 doi: 10.1016/j.jhep.2020.04.032[published Online First: Epub Date]|.
Tyritzis SI, Wiklund NP. Ureteral strictures revisited…trying to see the light at the end of the tunnel: a comprehensive review. J Endourol 2015;29(2):124-36 doi: 10.1089/end.2014.0522[published Online First: Epub Date]|.
Byun SS, Kim JH, Oh SJ, Kim HH. Simple retrograde balloon dilation for treatment of ureteral strictures: etiology-based analysis. Yonsei medical journal 2003;44(2):273-8 doi: 10.3349/ymj.2003.44.2.273[published Online First: Epub Date]|.
Tyritzis SI, Hosseini A, Collins J, et al. Oncologic, functional, and complications outcomes of robot-assisted radical cystectomy with totally intracorporeal neobladder diversion. Eur Urol 2013;64(5):734-41 doi: 10.1016/j.eururo.2013.05.050[published Online First: Epub Date]|.
Richter F, Irwin RJ, Jr., Watson RA, Lang EK. Endourologic management of malignant ureteral strictures. J Endourol 2000;14(7):583-7 doi: 10.1089/08927790050152195[published Online First: Epub Date]|.
Lang EK, Glorioso LW, 3rd. Antegrade transluminal dilatation of benign ureteral strictures: long-term results. AJR. American journal of roentgenology 1988;150(1):131-4 doi: 10.2214/ajr.150.1.131[published Online First: Epub Date]|.
Netto Júnior NR, Ferreira U, Lemos GC, Claro JF. Endourological management of ureteral strictures. J Urol 1990;144(3):631-4 doi: 10.1016/s0022-5347(17)39541-1[published Online First: Epub Date]|.
Chang R, Marshall FF, Mitchell S. Percutaneous management of benign ureteral strictures and fistulas. J Urol 1987;137(6):1126-31 doi: 10.1016/s0022-5347(17)44426-0[published Online First: Epub Date]|.
Lu C, Zhang W, Peng Y, et al. Endoscopic Balloon Dilatation in the Treatment of Benign Ureteral Strictures: A Meta-Analysis and Systematic Review. J Endourol 2019;33(4):255-62 doi: 10.1089/end.2018.0797[published Online First: Epub Date]|.
Kaouk JH, Garisto J, Eltemamy M, Bertolo R. Robot-assisted surgery for benign distal ureteral strictures: step-by-step technique using the SP(®) surgical system. BJU Int 2019;123(4):733-39 doi: 10.1111/bju.14635[published Online First: Epub Date]|.
Geavlete P, Nită G, Georgescu D, Mirciulescu V. Endoscopic classification and endourologic therapy in proximal incomplete ureteral duplication pathology. Eur Urol 2001;39(3):304-7 doi: 10.1159/000052458[published Online First: Epub Date]|.

Due to technical limitations, table 1 is only available as a download in the Supplemental Files section.

Download PDF

Review #2 received at journal
01 May, 2021
Editorial decision: Major revision
01 May, 2021
Review #1 received at journal
05 Apr, 2021
Reviewer #2 agreed at journal
21 Mar, 2021
Reviewer #1 agreed at journal
08 Mar, 2021
Editor assigned by journal
05 Mar, 2021
Reviewers invited by journal
05 Mar, 2021
Submission checks completed at journal
02 Mar, 2021
Editor invited by journal
01 Mar, 2021
First submitted to journal
23 Feb, 2021

You are reading this latest preprint version

A Nomogram to Predict Stricture-free Survival in Patients with Ureteral Stricture after Balloon Dilation

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Results

Discussions

Conclusion

Abbreviations

Declarations

References

Tables

Supplementary Files

Status:

Version 1