Data were collected retrospectively from EDGE, a con- sortium of North American tertiary care kidney stone centers formed in 2013. Overall 6 of the centers participated in the study (University of British Columbia, Mayo Clinic, New York University, Vander- bilt University, University of California San Diego, Ohio State University). A total of 232 subjects who had residual fragments after URS between 2006 and 2013 were identified. Data were securely stored electronically using REDCap™ software at Mayo Clinic, Scottsdale. The protocol was approved at each institution by their respective institutional review boards. Subjects with any size fragment(s) after the procedure with at least a KUB (with or without US) or CT within 12 months were included in the study. US alone was not used for the detection of fragments and was always correlated with KUB. Subjects had at least 12 months of follow- up. Subject demographics including age, gender, BMI, family history of stones, previous history of stones, previous stone procedures, diabetes, dyslipidemia and hypertension were reported with mean, median and proportions.
Primary Outcome
The primary outcome measured was the proportion of stone events defined as a composite of stone growth (at least 1 mm), stone passage, re-intervention or post- operative complications. Re-intervention for residual fragments was defined as the patient requiring an ancillary procedure such as SWL, URS, PNL, ureteral stent placement or percutaneous nephrostomy tube insertion. Com- plications were defined as recurrence of stone symptoms, stone related emergency room visit, stone related hospital admission or renal insufficiency (a greater than 1.5x in- crease in serum creatinine from preoperative level).
Secondary Outcomes
Secondary outcomes included proportion of stone growth, stone passage after ureteroscopy, re-intervention and complications. Based on literature showing that stone clearance correlates to fragment size, we compared secondary outcomes using a cutoff of 4 mm or less and greater than 4 mm for the largest fragment. The number of fragments was also recorded.
Inferential Statistics
Univariate analysis was performed to determine significant predictive variables for the primary and secondary outcomes, and they were reported using odds ratios with 95% CIs. These predictive variables included gender, age, BMI, history of stone episodes, stone location (upper calyx, mid calyx, lower calyx), intervention method (dusting or basketing) and stone laterality. The number of original stones, the size of the largest original stone, the number of fragments at followup, the size of the largest fragment and fragment locations were examined as potential predictors of events after URS. Significant predictor variables were then modeled into multivariate logistical regression analysis and these were reported using odds ratios with 95% CIs.
Logistic regression analysis was performed to deter- mine predictors of complication and re-intervention, with Kaplan-Meier survival curves constructed for subjects analyzed to compare the dusting technique compared to the basketing technique, with failure determined as re- intervention. A type I error of a¼0.05 was assumed. All statistical analysis was performed in R 3.1.1. Package pROC version 1.7.3 was used to analyze and plot survival data.
Among the 6 centers 232 patients had fragments after ureteroscopy. Mean followup was 16.76 ± 19.01 months. There was no difference in gender, age, BMI or history of stones between the groups. Of the patients with fragments 131 (56%) required no further intervention and remained asymptomatic.
The primary outcome demonstrated that 101 (44%) subjects experienced a stone event. Secondary out-comes demonstrated that 67 (29%) of all subjects required re-intervention and 34 (15%) experienced a complication from the stone fragment but did not require re-intervention. Univariate analysis demonstrated no difference in the passage of fragments that were 4 mm or smaller vs larger than 4 mm. Thus, any residual fragment (of any size) had a 26% to 27% chance of passing spontaneously after URS and 73% to 74% of fragments remained at followup. Despite no differ- ence in the passage of fragments, those larger than 4 mm were more likely to grow with time (p <0.001), were associated with significantly more complica- tions (p¼0.039) or required more re-intervention (p¼0.01). Subanalysis of those fragments 2 mm or smaller vs larger than 2 mm demonstrated that those fragments larger than 2 mm were more likely to grow with time (p <0.001). However, there were no statistical differences between those 2 mm or smaller vs greater than 2 mm for other outcomes (passage of fragments p¼0.15, complications p¼0.19 and re-intervention p¼0.14).
The most common complications were emergency department visit (17.2%) and recurrence of colic symptoms (15.1%). Renal insufficiency occurred in a small number of patients (2.6%) and 6.5% of pa- tients were hospitalized. Re-intervention was pre- dictable based on larger fragment size (OR 1.12, 95% CI 1.02e1.23, p¼0.017) and lower pole frag- ment location (p¼0.02). Of the 67 subjects who un- derwent re-intervention 32 did so electively, or for pain, stone growth, recurrent urinary tract infection or infection.
Original stone size before ureteroscopy was not predictive of subsequent re-intervention (OR 1.0, 95% CI 0.92e1.2, p¼0.507). Re-intervention was predicted based on the size of the largest fragment (OR 1.1, 95% CI 1.0e1.2, p¼0.02). There was a trend toward older age and re-intervention that did not quite meet statistical significance (OR 0.98, 95% CI 0.75e3.2, p¼0.07, table 1). The most common loca- tion of fragments was the lower pole of the kidney (table 2). The types of re-intervention included ureteroscopy in 58 cases (79.9% of re-interventions), PNL in 4 (6.1%) and SWL in 3 (4.5%). The tech- niques of dusting the stone vs fragmenting and basketing fragments were not a significant factor in the logistic regression. Overall 78 subjects were treated with the dusting technique, in which stones are lasered into dust to pass spontaneously, and 150 patients underwent the basketing procedure, in which stones are fragmented and extracted via a basket at the intervention (fig. 1). The effect of technique was not significant in a multivariable lo- gistic regression model. Kaplan-Meier analysis showed that larger residual fragments (greater than 4 mm) were more likely to require re-intervention (p¼0.004). Figure 2 demonstrates that the median time to a subsequent stone event is shorter in the presence of larger fragments (greater than 4 mm).
Stone disease in the U.S. is costly to the health care system. The cost was estimated at $3.79 billion in 2007 and will increase to $4.57 billion by 2030.8 In this multi-institutional cohort study we report that almost half (44%) of the subjects with residual fragments after ureteroscopy experienced a subse- quent stone event. Our data also show that any fragments, 4 mm or smaller and larger than 4 mm, surprisingly, have a similar chance (26% to 27%) of passing spontaneously after ureteroscopy. However, the fragments larger than 4 mm had a significantly higher rate of stone growth, events or requirement for re-intervention. The re-intervention rate was more than twice as high in patients with fragments larger than 4 mm (38% vs 18%, p¼0.001). The re- intervention rate of 18% for patients with frag- ments 4 mm or smaller was similar to that of 19.6% described by Rebuck et al.6 However, when looking at stones larger than 4 mm, the re- intervention rate was significantly higher in our study (38%, p¼0.001), lending evidence to treat patients with fragments larger than 4 mm pre- emptively. Further evidence to treat these patients preemptively is that complications were also more significantly likely to arise in patients with larger (greater than 4 mm) fragments (59.2% vs 27.8%, p¼0.039). These data show that rendering patients completely stone-free is the best way to ensure that they do not have subsequent problems from a particular stone or its fragments.
Our data concur with those reported by Raman et al, who found that patients with fragments larger than 2 mm after PNL were statistically more likely to have a stone related event.5 Furthermore, those residual stones in the renal pelvis or ureter were the most likely to cause problems. The delin- eation used in the study by Raman et al was frag- ments larger than 2 mm vs stones 2 mm or smaller.
In patients with fragments after SWL Osman et al found that 21% had stone regrowth and 79% passed fragments less than 4 weeks after the pro- cedure.1 The difficulty in comparing these results to our data is that the authors did not report the sizes of the residual fragments. Nevertheless, among all patients with fragments the 21% regrowth rate was similar to our findings for stones 4 mm or smaller.
In contrast, Khaitan et al found that 47% of patients after SWL had stone regrowth and that this rate increased with increasing original stone size.2 This rate is more in keeping with the 38% re- intervention rate and 59.2% rate of fragment growth that we found in our patients with fragments larger than 4 mm. Similar rates were also published in patients after SWL, as the re- intervention rate was 69% for those with residual fragments larger than 4 mm and only 21% for those with fragments 4 mm or smaller.9
Patients should be counseled that if they have fragments after ureteroscopy, they have a 26% chance of passing the fragment, but they might want to consider preemptively undergoing another procedure to remove the fragments, particularly those larger than 4 mm. In those patients with fragments 4 mm or smaller, there is still an 18% chance of re-intervention and 28% chance of com- plications. However, these occur significantly less often than in those with stones larger than 4 mm. In subanalysis using a 2 mm cutoff, the greater than 2 mm fragment did not pose as great a risk as it was only associated with growing larger but not with complications or re-intervention. This finding makes sense as smaller fragments (4 mm or smaller) should not cause clinical sequelae.
The choice of imaging modality is important in determining the size and location of residual fragments with CT as the gold standard, KUB plain film radiography with a sensitivity of 70.5% and US with a sensitivity of 52.5%.10 The sensitivity of KUB (85.7%) and US (57.1%) increased when using a stone size cutoff of greater than 4 mm.
A small subset of our analysis involved comparing the ureteroscopic techniques of dusting the stone so that the small pieces would pass spontaneously vs fragmenting the stones and actively basketing out the fragments. There was a statistically significant difference between the 2 groups. However, the difference in technique was not significant in a multi- variable logistic regression model. Patients who had stones dusted had a shorter time to a subsequent stone event, ie an ancillary procedure. Basketing stone fragments resulted in a decreased need for subsequent stone surgery in the followup period. Other studies in the literature have not been able to support one technique over the other and results have been equivocal.11 Even when stones are actively retrieved with a basket, the stone-free rate has been reported as 55% on postoperative CT.12 A more definitive prospective trial comparing these 2 techniques is currently under way by the EDGE Research Consortium.
Our study is limited by the retrospective nature of our data. The denominator of the total number of ureteroscopies at all centers was not recorded. Therefore, we do not know the stone-free rate at each institution or for the entire cohort. However, the purpose of this study was to evaluate the fate of stone fragments after ureteroscopy. We presumed these were fragments from the original surgery rather than newly formed stones, but theoretically these could be newly formed stones. One of the limitations of our retrospective data is that we were unable to ascertain the exact reasons why people had re-intervention. Was it because of the recurrence of symptoms or was it simply planned to treat the patient because of the residual fragment? This is unknown in our data set, but we can say that patients with larger residual fragments did end up undergoing more re-interventions. Even without knowing the exact reasons for triggering re- intervention, the complication rate was significantly higher, which alone could account for the increased rate of re-intervention. Likely the results indicate that large fragments are more likely to cause pain and lead to re-intervention. The rate of re-intervention correlated with the presence of large fragments, with 38% of those subjects requiring additional care.
Another limitation includes the lack of consistent postoperative imaging since it included CT or KUB with US. Despite the discrepancies in size measurements among these modalities, this reflects common practice patterns in urology. It can be argued that there is little discrepancy in size measurement between CT and combined KUB and US.
The study results suggest that fragment size greater than 4 mm after ureteroscopy is associated with significantly higher rates of stone growth, complications and the need for re-intervention with at least 1 year of followup. Even among fragments 4 mm or smaller 28% of stone fragments grew, 18% of patients underwent re-intervention and 22% experienced a complication, challenging the traditional description of CIRF. Patients with fragments larger than 4 mm should be counseled that they have a 38% chance of requiring re-intervention and a 59% chance of having a complication from that fragment. These data strongly support the preemptive treatment of patients with fragments larger than 4 mm. Those patients with fragments 4 mm or smaller have a lower risk of further problems but should be monitored. Ensuring complete stone-free status is the best way to reduce the rate of complications and interventions after ureteroscopy.
Mr. and Mrs. Charles and Anna Miller provided philanthropic support for the REDCap database and statistical services at Mayo Clinic, Arizona. Yu-Hui Chang conducted the statistical analysis and Olga Arsovska (UBC) provided assistance with the institutional research board approval.
Written By: Ben H. Chew,*,† Hilary L. Brotherhood,‡ Roger L. Sur,‡ An Qi Wang,‡ Bodo E. Knudsen,‡ Courtney Yong,‡ Tracy Marien,‡ Nicole L. Miller,§ Amy E. Krambeck,‡ Cameron Charchenko‡ and Mitchell R. Humphreysk
From the University of British Columbia, Vancouver, British Columbia, Canada (BHC, HLB), University of California San Diego, La Jolla, California (RLS, AQW), Ohio State University, Columbus, Ohio (BEK, CY), Vanderbilt University, Nashville, Tennessee (TM, NLM), Mayo Clinic, Rochester, Minnesota (AEK, CC), and Mayo Clinic Arizona, Phoenix, Arizona (MRH)
Read the Abstract
Reference:
1. Osman MM, Alfano Y, Kamp S et al: 5-Year- follow-up of patients with clinically insignificant residual fragments after extracorporeal shock- wave lithotripsy. Eur Urol 2005; 47: 860.
2. Khaitan A, Gupta NP, Hemal AK et al: Post- ESWL, clinically insignificant residual stones: reality or myth? Urology 2002; 59: 20.
3. Candau C, Saussine C, Lang H et al: Natural history of residual renal stone fragments after ESWL. Eur Urol 2000; 37: 18.
4. Delvecchio FC and Preminger GM: Management of residual stones. Urol Clin North Am 2000; 27: 347.
5. Raman JD, Bagrodia A, Gupta A et al: Natural history of residual fragments following percutaneous nephrostolithotomy. J Urol 2009; 181: 1163.
6. Rebuck DA, Macejko A, Bhalani V et al: The natural history of renal stone fragments following ureteroscopy. Urology 2011; 77: 564.
7. Streem SB, Yost A and Mascha E: Clinical implications of clinically insignificant store fragments after extracorporeal shock wave litho- tripsy. J Urol 1996; 155: 1186.
8. Antonelli JA, Maalouf NM, Pearle MS et al: Use of the National Health and Nutrition Examination Survey to calculate the impact of obesity and diabetes on cost and prevalence of urolithiasis in 2030. Eur Urol 2014; 66: 724.
9. Sahin C, Tuncer M, Yazici O et al: Do the residual fragments after shock wave lithotripsy affect the quality of life? Urology 2014; 84: 549.
10. Gokce MI, Ozden E, Suer E et al: Comparison of imaging modalities for detection of residual fragments and prediction of stone related events following percutaneous nephrolitotomy. Int Braz J Urol 2015; 41: 86.
11. Ghani KR and Wolf JS: What is the stone-free rate following flexible ureteroscopy for kidney stones? Nat Rev Urol 2015; 12: 281.
12. Portis AJ, Rygwall R, Holtz C et al: Ureteroscopic laser lithotripsy for upper urinary tract calculi with active fragment extraction and computer- ized tomography followup. J Urol 2006; 175: 2129.
From the University of British Columbia, Vancouver, British Columbia, Canada (BHC, HLB), University of California San Diego, La Jolla, California (RLS, AQW), Ohio State University, Columbus, Ohio (BEK, CY), Vanderbilt University, Nashville, Tennessee (TM, NLM), Mayo Clinic, Rochester, Minnesota (AEK, CC), and Mayo Clinic Arizona, Phoenix, Arizona (MRH)
Read the Abstract
Reference:
1. Osman MM, Alfano Y, Kamp S et al: 5-Year- follow-up of patients with clinically insignificant residual fragments after extracorporeal shock- wave lithotripsy. Eur Urol 2005; 47: 860.
2. Khaitan A, Gupta NP, Hemal AK et al: Post- ESWL, clinically insignificant residual stones: reality or myth? Urology 2002; 59: 20.
3. Candau C, Saussine C, Lang H et al: Natural history of residual renal stone fragments after ESWL. Eur Urol 2000; 37: 18.
4. Delvecchio FC and Preminger GM: Management of residual stones. Urol Clin North Am 2000; 27: 347.
5. Raman JD, Bagrodia A, Gupta A et al: Natural history of residual fragments following percutaneous nephrostolithotomy. J Urol 2009; 181: 1163.
6. Rebuck DA, Macejko A, Bhalani V et al: The natural history of renal stone fragments following ureteroscopy. Urology 2011; 77: 564.
7. Streem SB, Yost A and Mascha E: Clinical implications of clinically insignificant store fragments after extracorporeal shock wave litho- tripsy. J Urol 1996; 155: 1186.
8. Antonelli JA, Maalouf NM, Pearle MS et al: Use of the National Health and Nutrition Examination Survey to calculate the impact of obesity and diabetes on cost and prevalence of urolithiasis in 2030. Eur Urol 2014; 66: 724.
9. Sahin C, Tuncer M, Yazici O et al: Do the residual fragments after shock wave lithotripsy affect the quality of life? Urology 2014; 84: 549.
10. Gokce MI, Ozden E, Suer E et al: Comparison of imaging modalities for detection of residual fragments and prediction of stone related events following percutaneous nephrolitotomy. Int Braz J Urol 2015; 41: 86.
11. Ghani KR and Wolf JS: What is the stone-free rate following flexible ureteroscopy for kidney stones? Nat Rev Urol 2015; 12: 281.
12. Portis AJ, Rygwall R, Holtz C et al: Ureteroscopic laser lithotripsy for upper urinary tract calculi with active fragment extraction and computer- ized tomography followup. J Urol 2006; 175: 2129.