344 CONTEMPORARY UROLOGICAL INTERVENTION FOR CYSTINURIC PATIENTS

limiting factor. Subsequent introduction of the pulsed dye laser, which could be performed via smaller, flexible uretero- scopes, was inapplicable for cystine stones recalcitrant to such fragmentation. Recently however, the introduction of the holmium laser has allowed safe and effective intrau- reteral lithotripsy of cystine calculi, and currently this is the approach of choice for most ureteral cystine stones requiring fragmentation. Retrograde endoscopy was planned for only 7 of our cases (11.5%), 5 of which required intracorporeal lith- otripsy. The 85.7% stone-free status is again likely a reflec- tion of patient selection with a relatively small stone burden (mean less than 1 cm.2) at the outset of treatment.

For the largest and most complex or extensively branched cystine calculi we have used a sandwich approach, combining percutaneous ultrasonic debulking with shock wave litho- tripsy of residual inaccessible infundibulocaliceal extensions, and secondary rigid and flexible nephroscopy as necessary. Our 50% stone-free rate in this setting is similar to that reported by Martin et al,S and clearly reflects the extensive nature of the initial stone burden in these few select patients.

Patient selection was perhaps the most important factor in achieving an overall stone-free status of 86.9%, and this selection process was equally important in minimizing mor- bidity. The overall success rate was achieved with no mor- tality, little morbidity and relatively short hospital stays. While 31 patients underwent 61 primary interventional pro- cedures and 14 secondary interventions, no patient required open operative intervention. This fact clearly suggests that while cystine stones may not be amenable to all contempo- rary forms of endourological intervention, proper patient se- lection allows applicability of 1 or more minimally invasive modalities to virtually any cystinuric patient requiring stone extirpation.

The avoidance of open operative intervention seems espe- cially important in this patient group, as the vast majority will eventually suffer recurrence, often within 1 to 2 years.1 As such, another goal of this study was to determine whether the type of intervention or the presence of residual calculi significantly influenced the probability of or time to stone recurrence. While Knoll et a1 suggested that residual stones following percutaneous management portend a relatively poor prognosis and rapid recurrence,8 it has been our expe- rience that virtually all cystinuric patients will suffer recur- rent stones and stone growth even while on optimal medical management.' Our patients undergoing percutaneous treat- ment had a relatively high probability of recurrence at 1 and 5 years, regardless of the absence or presence of residual stones &r initial treatment. In fact, the probability of a recurrence at 1 and 5 years was relatively high in all of our patients, and this risk was uniformly independent of the type of procedure performed and whether there were residual stones. However, while the probability of recurrence was not significantly different in the presence or absence of residual stones, the time to recurrence in the absence of residual stone was clearly longer. This finding is especially important in view of the fact that the majority (68%) of our patients with cystine stone recurrences required subsequent intervention.

Again the natural history of cystinuria is clearly frequent recurrence even with or despite medical management.' In this study the 0.55 probability of recurrence at 5 years was more than twice as great for those with cystine excretion greater than 797 mg./gm. creatinineJ24 hours compared to the 0.22 probability for those with lower levels. As the study group was limited to 31 patients, the lack of a statistically significant difference in these rates may simply represent the limited sample size.

1

CONCLUSIONS

Despite appropriate medical management, cystinuric pa- tients tend to suffer frequent recurrences that require uro-

ogical intervention. We determined that the type of inter- {ention performed had little influence on the rate of stone recurrence. We also found that while rendering these pa- tients stone-free did not significantly decrease the probabil- ity of recurrence, the interval to that recurrence was ex- tended. The benefit of this is obvious, considering the high incidence of intervention required for such recurrences.

While cystine stones are not amenable to all currently available minimally invasive therapeutic modalities, we were able to achieve an overall stone-free rate of 86.9% with- out any open operative procedures. As such, we conclude that cystinuric patients clearly can benefit from contemporary intervention. When such intervention is used selectively, with consideration given primarily to the stone burden and location, rates of recurrence will relate primarily to the nat- ural history of the medically treated cystinuric patient, and not the type of intervention used.

REFERENCES

1. Chow, G. K. and Streem, S. B.: Medical treatment of cystinuria: results of contemporary clinical practice. J. Urol., 156 1576, 1996.

2. Diggle, P. J., Liang, K. and Zeger, S. C.: Generalized linear models for longitudinal data. In: Analysis of Longitudinal Data. Edited by P. J. Diggle, K. Liang and S. C. Zeger. New York Oxford University Press, pp. 143-145, 1994.

3. Hernandez-Graulau, J. M., Castaneda-Zuniga, W., Hunter, D. and Hulbert, J. C.: Management of cystine nephrolithiasis by endourologic methods and shock-wave lithotripsy. Urology, 34: 139, 1989.

4. Katz, G., Kovalski, N. and Landau, E. H.: Extracorporeal shock- wave lithotripsy for treatment of ureterolithiasis in patients with cystinuria. Brit. J. Urol., 7 2 13, 1993.

5. Harada, M., Zhao-Ren, K. and Kamidono, S.: Experience with extracorporeal shock wave lithotripsy for cystine calculi in 20 renal units. J. Endourol., 6 213, 1992.

6. Bhatta, K. M., Prien, E. L. and Dretler, S. P.: Cystine calculi- rough and smooth a new clinical distinction. J. Urol., 142 937, 1989.

7. Kachel, T. A., Vijan, S. R. and Dretler, S. P.: Endourological ewerience with cvstine calculi and a treatment algorithm. J. Urol., 145 25, i m . -

8. Knoll, L. D., Semra, J. W., Patterson, D. E., Leroy, A. J. and Smith, L. H.-Long-term followup in patients with cystine urinary calculi treated by percutaneous ultrasonic lithotripsy. J. Urol., 140 246, 1988.

9. Martin, X., Salas, M., Labeeuw, M., Pozet, N., Gelet, A. and Dubernard, J. M.: Cystine stones: the impact of new treat- ment. Brit. J. Urol., 68: 234, 1991.

EDITORIAL COMMENT This article is an excellent summary of the results of the use of the

current endourological algorithm for treatment of cystine stone dis- ease, that is ureteroscopy for lower ureteral cystine stones, ureteros- copy or percutaneous nephrostolithotomy for upper ureteral cystine stones greater than 1.5 cm., ESWL for upper ureteral or renal cys- tine stones less than 1.5 cm., percutaneous removal of cystine renal stones greater than 1.5 cm. in diameter and sandwich therapy (per- cutaneous nephrostolithotomy/ESWL) for branched cystine calculi. The authors also report that 74% of all stone episodes (45/61) re- quired percutaneous intervention and that, regardless of the pres- ence or absence of residual stones, 73% of patients will have recur- rence within 5 years.

Unless a patient can take penicillamine or a-mercaptopro- prionylglycine (and those we see usually cannot), it is a rare cystine stone former who can avoid recurrent stone disease. Even with alkalization, cystine crystallization will occur when the concentra- tion exceeds 250 mg./l. Thus, urinary cystine excretion greater than 750 mgJday requires a t least 3 1. of urine output to prevent crystal- lization, which is achievable but hard to maintain. Therefore, we can expect all cystine stone formers unable to take penicillamine or a-mercaptoproprionylglycine who excrete greater than 750 mg. cys- tine daily (most homozygotes excrete at least this amount) to form

CONTEMPORARY UROLOGICAL INTERVENTION FOR CYSTINURIC PATIENTS 345

not have adequate followup. Use of the current algorithm has re- sulted in far too many potentially hazardous percutaneous interven- tions.

stones, despite adequate alkalization. This is the reason the recur- rence rate is 73% at 5 years and approximately that many cystine stone patients can expect to have recurrence in the next 5 years and again in the 5 years after that and in each succeeding 5-year period until the disease decreases in severity, as it appears to do after the fiRh decade. Massachusetts General Hospital

Although these authors have reported superb results and low complication rate of percutaneous nephrostolithotomy, the question that must be asked is what can we do to prevent the need for

Stephen P. Dretler

Boston, Massachusetts

REPLY BY AUTHORS percutaneous treatment in 74% of these patients and the high like- lihood that the procedure will be repeated many times in their lifetime. At our institution we have altered the algorithm slightly to reduce the necessity of percutaneous intervention. ESWL is offered to cystine stone patients, symptomatic or not, when the stone size measured by computerized tomography approximates 1 cm. in great- est dimension. Retrograde ureterorenoscopy with holmium:YAG or electrohydraulic lithotripsy is used as an alternative to percutaneous nephrostolithotomy for renal stones 1.6 to 3.0 em. in greatest diam- eter. These 2 slight shifts in strategy have significantly reduced the number of percutaneous interventions and limited percutaneous ne- phrostolithotomy to either first time stone formers or those who do

Cystinurics are prone to frequent stone recurrence despite our best efforts at medical control, and any approach that might reduce the frequency of invasive intervention is welcomed. In our study the 45 percutaneous procedures were performed on 25 patients of whom 17 (68%) were in fact undergoing the first procedure at our center. As such, the impact of the suggested altered algorithm for this majority of cystinuric patients is unclear. On the other hand, 2 of our most difiicult to control cases accounted for 15 (33%) of the percutaneous procedures. The role of aggressive prophylactic intervention, a t least in this small subset of patients, could ultimately prove to be of considerable value.