SEARCH

SEARCH BY CITATION

Keywords:

  • calculi;
  • nomograms;
  • transurethral ureterolithotripsy

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

Objectives

To develop and to internally validate a novel nomogram for predicting the stone-free rate after transurethral ureterolithotripsy.

Methods

A total of 412 patients with 534 ureteral stones were treated with transurethral ureterolithotripsy using semi-rigid ureteroscopes. Treatment efficacy was evaluated 3 months after the procedure. Multivariate stepwise logistic regression analysis was used to identify independent predictors of being stone-free in the model-building set. A total of 427 stones (80% of 534) were randomly allocated for identification and statistical analysis to build the model, and the remaining 107 (20%) were used for cross-validation. A nomogram for the stone-free rate was developed based on the final logistic regression model.

Results

Stone length, number of stones, stone location and the presence of pyuria were independent factors related to the stone-free rate after transurethral ureterolithotripsy treatment, and these were used to develop a nomogram. In this nomogram, the area under the receiver operating characteristic curve was 0.7432 for the nomogram, 0.5641 for stone size, 0.5908 for the number of stones, 0.6594 for stone location and 0.6076 for pyuria. Validation using 20% of the data also achieved a reasonable predictive accuracy (area under the receiver operating characteristic curve = 0.682).

Conclusions

The first nomogram for predicting the stone-free rate after transurethral ureterolithotripsy was developed. It has a reasonable predictive accuracy, and in combination with extracorporeal shock wave lithotripsy nomograms, it might be useful for deciding treatment methods.


Abbreviations & Acronyms
AUC

area under the receiver operating characteristic curve

BMI

body mass index

CI

confidence interval

CT

computed tomography

EAU

European Association of Urology

EBM

evidence-based medicine

ESWL

extracorporeal shock wave lithotripsy

f-TUL

flexible-transurethral ureterolithotripsy

KUB

kidney–ureter–bladder plain X-ray

ROC

receiver operating characteristic

TUL

transurethral ureterolithotripsy

WBC+

positive white blood cells

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

TUL is a method for treating ureteral stones transurethrally by removing them through an endoscope inserted in a retrograde fashion into the ureter. Together with ESWL, TUL is now an established method for the treatment of ureteral stones.[1-6] It is currently recommended in the EAU guidelines as an appropriate treatment for cases of ureteral stones based on EBM criteria.[1] Selection of the procedure for active ureteral stone removal depends on stone location and size. For stones in the proximal ureter, ESWL is recommended as the first-choice treatment for stones <10 mm, and TUL (anterograde or retrograde) or ESWL is recommended for stones ≥10 mm. For stones in the distal ureter, ESWL or TUL is recommended as first-choice treatment for stones <10 mm, and TUL is recommended as the first choice for stones ≥10 mm in this location.

Depending on individual cases, however, it might be difficult to determine whether ESWL or TUL is the more appropriate choice of treatment. In such cases, pretreatment prediction of the stone-free rate for each type of treatment might enable selection of the optimal treatment for ureteral stones in individual patients. With respect to urological tumors, nomograms have been developed as prognostic and predictive tools for predicting the cancer detection rate of prostate biopsy in prostate cancer, as well as pathological staging after radical prostatectomy.[7-16]

With respect to ureteral stones, however, although some models for predicting the outcome of ESWL have been previously reported,[17-19] there has not been a nomogram for predicting the outcome of TUL. In the present study, a nomogram for predicting the stone-free rate in TUL treatment of ureteral stones was developed and internally validated.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

Study population

Between April 2002 and May 2010, data were collected during the routine clinical care of patients; 412 patients with 534 ureteral stones were treated with TUL at Chiba University Hospital, Funabashi Clinic, and Chiba Municipal Aoba Hospital in Chiba, Japan. The urinary stones were diagnosed by KUB and/or non-contrast CT; radiolucent stones were excluded from this series. Any previous treatments were allowed and all stone-free cases were treated by only a single treatment with TUL. There are no bilateral TUL cases with a single treatment.

Stone length was based on the maximum length on KUB and/or CT, and the number of stones was classified as one stone, two stones, three stones and four or more stones. Stone location was categorized by ureteropelvic junction, proximal ureter, middle ureter and distal ureter. In the preoperative analysis, pyuria positive was defined as at least WBC+ on general urinalysis and/or ≥5 WBC/high power field on examination of urinary sediment. In the present study, we did not define pyuria as urine culture positive. All patients underwent TUL under general anesthesia or lumbar spinal anesthesia. TUL was carried out using semi-rigid ureteroscopes, and the energy source was a Ho:YAG laser and/or electrohydraulic lithotripsy. Treatment efficacy was evaluated by a KUB and/or CT 3 months after each TUL, and stone-free was defined as no fragments detected on KUB and/or CT. The cases that showed small fragments after TUL were excluded from the stone-free category.

Statistical analysis

To develop the nomogram, 427 out of 534 stones (80%) were randomly selected to build the model, whereas the remaining 107 stones (20%) were reserved to validate the model. Wilcoxon rank sum test and Fisher's exact test were used to determine the differences between the training and the validation data set. The factors evaluated for the predictors of being stone-free after TUL included age, BMI, sex, stone length, side, number of stones, stone location and pyuria on urinalysis. The significance of each factor was assessed on t-test for continuous variables and Fisher's exact test for category variables.

Multivariate stepwise logistic regression analysis was used to determine which factors were independent predictors of being stone-free in the model-building set. Odds ratio and 95% CI were also derived. A nomogram for the stone-free rate was developed based on the final logistic regression model. Using the validation data set, ROC curves were used to compare the performance of the model with the prediction based on stone length, number of stones, location and pyuria. Performance characteristics were examined by calibration plots. Logistic regression analyses were carried out using R software (http://www.r-project.org/). Wald test was also used to determine the overall P-values for each categorized variable.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

Patient data

Table 1 shows the characteristics of the enrolled study population. The means ± standard deviation of age, BMI and stone length were 57.17 ± 13.38 years, 24.26 ± 3.98 kg/m2 and 8.94 ± 5.58 mm, respectively. The stone location was the ureteropelvic junction for 15 stones, the proximal ureter for 216 stones, the mid ureter for 115 stones and the distal ureter for 188 stones. Pyuria was positive for 292 (54.7%) of the 534 stones. There were not any statistically significant differences between the training and the validation data set.

Table 1. Clinical characteristics and results of 412 patients with 534 stones
Variable

Total stones

(n = 534)

Training data setValidation data setP-value
Stones (n = 427)Stones (n = 107)
Stone-free rate (%)81.381.082.20.239
Age (years)57.17 ± 13.3857.14 ± 13.3757.11 ± 13.440.760
BMI (kg/m2)24.26 ± 3.9824.27 ± 4.0424.01 ± 3.660.838
Stone length (mm)8.94 ± 5.588.98 ± 5.118.88 ± 7.150.393
Sex   0.588
Male29724057
Female23718750
No. stones   0.671
132326163
21088525
3574317
≥4463817
Side   0.829
Right26721552
Left26721255
Location   0.417
Ureteropelvic junction15114
Proximal ureter21617838
Middle ureter1158728
Distal ureter18815137
Pyuria   0.128
Positive29222666
Negative24220141

Surgery results

Of the 534 stones, 434 were stone-free 3 months after TUL, for a stone-free rate 3 months after TUL of 81.3% (434 of 534 stones; Table 1). Table 2 shows the patient distribution for each variable and the results of the univariate and multivariate analyses that evaluated the factors associated with being stone-free.

Table 2. Patient distribution and statistical analysis of the predictors for being stone-free 3 months after TUL
VariableStonesStone-freeUnivariate analysisMultivariate analysis
P-valueOdds ratio95%Confidence intervalP-valueOverall P-value
Stone length427346 (81.0%)0.0190.920.875–0.9670.0010.001
Sex       
Male240191 (79.6%)0.388    
Female187155 (82.9%)     
No. stones       
1261222 (85.1%) 1(Reference) 0.034
28567 (78.8%)0.0420.5680.281–1.1460.114
34330 (69.8%)0.0270.4180.178–0.9790.045
≥43827 (71.1%)0.0440.3210.134–0.7730.011
Side       
Right215171 (79.5%)     
Left212175 (82.5%)0.456    
Location       
Ureteropelvic junction113 (27.2%) 1(Reference) <0.001
Proximal ureter178132 (74.2%)0.0048.7022.03–37.2990.004
Middle ureter8776 (87.4%)<0.00118.3473.909–86.118<0.001
Distal ureter151135 (89.4%)021.4234.767–96.279<0.001
Pyuria       
Negative201177 (88.1%) 1(Reference) 0.030
Positive226169 (74.8%)0.0010.5370.306–0.9420.030

Development of a nomogram

Table 2 shows the significant predictors for being stone-free after TUL in order of statistical significance on t-test. The stepwise multivariate logistic regression analysis identified four significant predictors for being stone-free in the study cohort (P < 0.05; Table 2). Independent analyses using forward and backward stepwise procedures yielded identical results. Using the four independent predictors, a nomogram was developed to predict the stone-free rate 3 months after TUL (Fig. 1). As described by Kattan et al.,[7] the accumulated number of points for each of the four categories was totalled to calculate the overall likelihood of being stone-free.

figure

Figure 1. Nomogram predicting stone-free rates 3 months after TUL. Directions: determine stone length, number of stones, stone location and pyuria on urinalysis for an individual patient. Draw a line upwards to the number of points in each category. Total the points, and then draw a line downward to find the probability of the patient being stone-free after TUL.

Download figure to PowerPoint

For example, according to the model (Fig. 1), a 64-year-old male with a 6-mm long stone in the left distal ureter and with a normal urinalysis had a predicted stone-free rate of 95.4%.

The calibration plots with local regression nonparametric smoothing lines of the present nomogram indicated good agreement between the predicted and actual probabilities (Fig. 2).

figure

Figure 2. Calibration plots with local regression non-parametric smoothing lines of the present nomogram. The x-axis represents nomogram-predicted probability of stone-free rate after TUL, and the y-axis represents actual probability of stone-free rate. image, Ideal; image, non-parametric; image, grouped observations.

Download figure to PowerPoint

In this nomogram, the AUC were 0.7432 for the nomogram itself, 0.5641 for stone size, 0.5908 for the number of stones, 0.6594 for stone location and 0.6076 for pyuria. Validation using 20% of the data also achieved a reasonable predictive accuracy (AUC = 0.682).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

It is generally preferable to develop nomograms using cohorts with little bias toward characteristics in order to establish their broad utility. With respect to TUL nomograms, it is thought to be particularly important to avoid extreme bias in treatment outcomes. In order to verify the validity of the cohort in this study, the current treatment outcomes were compared with those for ureteral stone treatment published in the 2011 EAU Guidelines. According to the 2011 EAU Guidelines, the median stone-free rates for TUL were 82%, 87% and 93% for the proximal, mid and distal ureter, respectively.[1] The corresponding stone-free rates for the present cohort were 75%, 88% and 89%, respectively, showing a somewhat lower rate for the proximal ureter. The reason for this might be that the Guidelines were based on a meta-analysis including cases in which flexible ureteroscopes were used, whereas the present cohort included only cases treated using semi-rigid ureteroscopes. In recent years, the availability of flexible ureteroscopes has led to better treatment outcomes compared with those for rigid ureteroscopes, particularly for proximal ureteral stones.[20] Thus, the treatment outcomes of the present cohort were almost equivalent to those of the Guidelines, and therefore constituted a valid cohort for the production of a universally applicable nomogram.

During the development of the nomogram, stone size, number of stones, stone location and the presence or absence of pyuria were shown to be independent factors determining the stone-free rate after TUL treatment. There are several reports about the factors related to the stone-free rate in TUL treatment. Yencilek et al. reported that the success rate of semi-rigid TUL was relatively low in the proximal ureter (71.7%) when compared with the mid (94.8%) and distal ureter (98.9%; P = 0.021).[21] El-Nahas et al. reported that significant factors for unfavorable TUL results were proximal ureteral stones, ureteroscopy carried out by surgeons other than experienced endourologists, stone impaction and stone width.[22] Leijte et al. reported that surgeon experience is a predictive factor for complications and success for TUL.[23]

Abe et al. suggested that pyuria is an independent factor predicting the stone-free rate after ESWL treatment.[24] In the present cohort, as for ESWL, pyuria was a predictive factor for the stone-free rate after TUL, and multivariate analysis also showed a significant difference. Although the reason why the stone-free rate becomes worse in the case of positive pyuria is unknown, it is assumed that in such cases with hydronephrosis by the impacted stone, hydronephrosis might cause pyuria, and it might decrease the stone-free rate by increasing the risk of push up by hydronephrosis and the difficulty of TUL because of the stone impaction.

It has also been reported that the longer length of the urethra in men affects mechanical operations during the procedure, meaning that the occurrence of complications is influenced by sex,[25] whereas other studies have reported that sex has no effect on the stone-free rate.[23] In the present cohort, the stone-free rates for men and women were 79.8% and 83.1%, respectively; the difference was not significant.

As aforementioned, a range of nomograms has been produced as prognostic and predictive models for treatment efficacy with respect to malignant urological tumors, but in terms of predictive models for ureteral stone treatment, there have been only a few previous reports regarding ESWL.[17-19] There has been no previous report of the development of a nomogram for predicting the efficacy of TUL treatment, and this is the first nomogram for TUL. In this nomogram, AUC were 0.7432 for the nomogram itself, 0.5641 for stone size, 0.5908 for the number of stones, 0.6594 for stone location and 0.6076 for pyuria. Validation using 20% of the data also achieved a reasonable predictive accuracy (AUC = 0.682), indicating that the nomogram had a reasonable accuracy using simple factors alone.

Although there are still a number of impediments, this nomogram might benefit us in choosing optimal treatment options by comparing predicted treatment outcomes of ESWL and TUL nomograms in the future.

However, this nomogram has some limitations. The first is that, although it is useful in practice for providing information to patients, prediction of treatment efficacy does not always lead to choice of actual treatment method. The second is that this nomogram's high predictive accuracy might not be maintained when it is used in other institutions because of differences in the operator's skill and in treatment policies among institutions. Because a high level of skill is required for ureteroscopic operations, it has been suggested that treatment outcomes are influenced by the operator's skill,[23] and the high predictive accuracy of this nomogram might not be maintained in other institutions. For this reason, external validation of this nomogram is required.

In addition, the introduction of f-TUL in recent years has also improved treatment outcomes for mid and upper ureteral stones (especially in men), and f-TUL has now been adopted by numerous institutions. However, from the global standpoint, there seems to be many institutions that still use only semi-rigid ureteroscopes. As the f-TUL nomogram cannot be applied to institutions using semi-rigid ureteroscopes, both semi-rigid TUL nomogram and f-TUL nomogram will be required for universal use. In the present study, we developed a nomogram for predicting treatment outcomes of TUL using only semi-rigid ureteroscopes. Production of a nomogram for predicting treatment outcomes of f-TUL will also be required in the future.

In terms of the future potential of nomograms for ureteral stones, it will be of value to establish nomograms to predict treatment efficacy for individual treatments, such as f-TUL and percutaneous nephrolithotripsy. By comparing predicted values between different treatment methods, we might objectively choose the most effective treatment based on individual patient characteristics. Although further studies are required, it is our hope that this nomogram will pioneer the development of new strategies for treatment choice.

The first nomogram for predicting the stone-free rate after TUL was developed. It has a reasonable predictive accuracy, and in combination with ESWL nomograms, it might be useful for deciding treatment methods in the future.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

Koji Kawamura is partially supported by a JFE (The Japanese Foundation for Research and Promotion of Endoscopy) Grant.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References