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MANAGEMENT OF RESIDUAL STONES
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MANAGEMENT OF RESIDUAL STONES Fernando C. Delvecchio, MD, and Glenn M. Preminger, MD
When open surgery was the standard treatment for the management of renal calculi, the presence of residual fragments suggested a failed procedure, even if those remaining fragments were small. Because residual calculi may act as a nidus for recurrent stone formation, complete stone removal was the principal goal of therapy? The introduction of shock-wave lithotripsy (SWL), however, shed a new perspective on this century-old concept, minimizing the importance of postprocedural residual fragments. Currently, most renal stones requiring treatment are managed by SWL.8 Stone-free rates following SWL, however, are highly dependent on stone location, size, number, and composition, as well as the degree of hydronephrosis and renal function of the ipsilateral renal unit.21,33 Approximately 66% to 72% of patients may be rendered stone-free if SWL is used for treatment of a wide variety of renal and ureteral lithia~is.'~, 29 Successful SWL results, however, now are defined by many reports as complete fragmentation of the original stone to fragments small enough to pass spontaneously, with no discomfort. Three months after SWL therapy, 28% to 34% of patients retain stone particles, and post-SWL fragments may take as long as 30 months to pass spontaneously."jConsequently, the principles of SWL therapy have changed com-
pletely the dogmas of open surgery, in which the aim was to render the patient completely stone-free at the completion of the operative procedure.
CLINICALLY INSIGNIFICANT RESIDUAL FRAGMENTS
In this age of SWL and other minimally invasive endoscopic stone-removal techniques, the significance and fate of residual fragments after treatment remains unclear. Clinically insign$cant residual fragment (CIRF) was a new term rapidly added to urologists' vocabulary with the advent of SWL, to address such posttreatment stones. Despite the widespread use of this term, there is no consensus regarding the maximum size or characteristics that stone fragments should have, if any, to be insignificant, avoiding growth, becoming symptomatic, or requiring interent ti on.^^ CIRFs usually are SWL residual fragments that are smaller than 4 mm (or sometimes 5 mm), asymptomatic, nonobstructive, noninfectious, and associated with sterile urine. By extension, this term also defines stones of similar characteristics left behind after percutaneous nephrostolithotomy or ureteroscopic procedures.
From the Division of Urology, Department of Surgery (FCD, GMF),and The Comprehensive Kidney Stone Center (GMP),Duke University Medical Center, Durham, North Carolina UROLOGIC CLINICS OF NORTH AMERICA
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DIAGNOSIS OF RESIDUAL FRAGMENTS
The most accurate diagnostic test to address the presence of residual fragments is probably nephroscopy, because some radiologic imaging studies may overestimate postprocedural stone-free rates.'2,39 Nephroscopy, however, for obvious reasons is routinely feasible postoperatively only in patients who recently have undergone a percutaneous nephrostolithotomy and still have a nephrostomy tube in place. The degree of overestimation of stone-free rates varies according to the different sensitivities of the individual imaging modalities. The initial report that compared endoscopic and radiological evaluation of residual fragment rates following percutaneous nephrolithotripsy and SWL demonstrated that plain abdominal radiographs and renal tomography overestimated stone-free rates by 35% and 17%, respectively, compared with flexible nephroscopy.'2 Moreover, studies have reported interobserver and intraobserver variability in radiographic review of residual fragment^?^ Plain abdominal films alone are the most difficult to interpret, resulting in the highest uncertainty (and hence observer variability) about 24 This fact the presence of residual results from the superimposition of bowel gas, feces, and soft-tissue calcifications. Obesity and the presence of faintly radioopaque nephrolithiasis also contribute to the misdiagnosis. Some reports have suggested that linear tomograms detect 13% to 46% more stones than originally reported by plain films.22,30, 45 Another study has documented that there is significantly less interobserver variability in the identification of stones with tomography than with plain radiographyz4 Reading plain abdominal films and tomograms together reduces even more inter- and intraobserver variability, and these differences are usually minor. Several reports have addressed the sensitivity of ultrasound in the detection of urolithiasis to be between 65% and %%?, 31 The advantage of ultrasound relies on the fact that all stones, independent of their composition, present an acoustic-impedance mismatch with the surrounding tissues, and attenuate sound to a greater degree. For these reasons, radiolucent and radioopaque stones appear as echogenic foci with an acoustic shadow behind. The diagnostic reliability of ultra-
sound falls dramatically, however, in scanning for stones in the ureter. Moreover, ultrasound is inadequate in quantifying the stone burden and generally does not permit differentiation of intact stones from fragmented ones.31Therefore, sonography should be used only as a complement to other conventional radiographic imaging studies and not on its own merits. In this setting, a combination of abdominal radiography and renal ultrasonography has been proven to be as good or better than intravenous urography in identifying residual stone fragments and intrarenal and perirenal abnormalities in a set of asymptomatic patients 1 month after SWL." The sensitivity of CT has been shown to be superior to plain radiography ( P < 0.05), linear tomography ( P < .05) and ultrasonography (P < .01)in detecting postprocedural residual stones.27Noncontrast spiral CT was demonstrated to be superior to plain radiography combined with sonography in determining size and location of renal and ureteric calculi.49Noncontrast spiral CT also was shown to have superior sensitivity and equal specificity to intravenous urography in detecting renal stones and demonstrates equal sensitivity in the detection of ureteral dilation. Compared with intravenous urography, CT can detect stones of various compositions adequately, and both studies are comparable in terms of overall costs and ionizing radiation delivered. CT and intravenous urography, however, can be upwards of three times as expensive as plain abdominal films or tomography. IMPORTANCE OF RESIDUAL FRAGMENTS
Residual fragments may be important for a variety of reasons: They may act as a nidus for recurrent stone growth, they can become dislodged acutely and cause significant obstruction with pain and infection, or they might be the source of persistent infection. After stone fragmentation or removal by any modality, the underlying metabolic abnormalities for recurrent stone formation persist.6 Supersaturation of the urine with stoneforming salts or lack of stone inhibitors may accelerate the growth of residual fragments, irrespective of their size, and promote new stone recurrence. Residual calculi may act as a nidus for stone growth by heterogeneous nucleation.
MANAGEMENT OF RESIDUAL STONES
This is a process in which particulate matter in the urine, such as other crystals, may act as nucleating foci. The saturation needed for heterogeneous nucleation is much less than for homogeneous nucleation. Crystallization can occur at lower chemical saturations than required for the formation of the initial stone nucleus.’ Crystal aggregation also may enhance the growth of pre-existing fragments. Several studies have stressed the long-term recurrence rates posed by postprocedural residual calculi because of the previously mentioned reasons. These investigations report stone-recurrence rates of 10% to 15% if the patient was rendered stone-free, in contrast to a 50% to 80% incidence of stone growth or new stone formation if residual stones were present after the SWL procedure.” 20, 32, 52 A recent report suggests that patients rendered stone-free by SWL demonstrate a higher stone-recurrence rate than a similar group of patients treated by percutaneous nephrolithotomy, without ultrasonic fragmentation? This study documents a significantly higher number of new stone recurrence in lower and midcalyces (compared with baseline location) after SWL than after percutaneous nephrolithotripsy. The results suggest that higher recurrence rates after SWL may be caused by microscopic sand particles migrating to dependent calyces and acting as a niduses for new stone formation. SWL, by dramatically increasing the surface area of the original stone, may favor new stone growth through heterogeneous nucleation, and crystal aggregation by exposing more stone area to the lithogenic environment. A recent prospective study followed 160 patients with 4-mm or smaller asymptomatic calcium oxalate or calcium phosphate stone fragments after SWL for a mean of 23 months to stone-free status, censorship, or intervention, in order to address the clinical implications of CIRFs. Stone-free status or a decreased, stable, or increased amount of residual stone occurred in 23.8%, 16.3%, 41.9%, and 18.1% of the 160 patients, respectively. Kaplan-Meier estimates of the probability of these outcomes at 5 years were 0.36 for spontaneously achieving a stone-free status, 0.53 for spontaneously achieving a stonefree or decreased stone status, and 0.80 for achievement of stone-free, decreased, or stable At follow up, however, 43.1% of patients had developed significant symptomatic episodes or needed intervention, and Kaplan-Meier estimates predicted this possi-
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bility to be around 70% if small residual fragments were left and follow-up was 5 years after SWL. Even investigators who believe in the existence of CIRFs do not consider retained calculi of struvite to be insignificant, because the urea-splitting bacteria necessary for the formation of these stones may persist in the remaining fragments, thus promoting a cycle of persistent infection and accelerated growth. In vitro studies demonstrate that crystal production by Pro teus rnirabdis, the commonest causative organism, can occur in only 4 Struvite stones tend to recur in 10% of cases after complete stone removal and in 85% of patients if stone remnants are left behind.’ Therefore, there is clear evidence in the literature that untreated postprocedural residual fragments pose a significant risk for stone recurrence or new stone growth. The authors consider CIRF to be a misnomer that leads to the acce tance of treatment failures and minimizes e importance of untreated stones within the urinary system.
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INCIDENCE AND CAUSE OF RESIDUAL STONES
The reported incidence of residual stones varies according to the treatment modality used. Several factors impact the resence of postprocedural residual stones. ey include stone composition, size, and location, as well as anatomy of the urinary tract. Clinical experience accumulated throughout the years has been able to idenhfy stone and anatomic characteristics that predict treatment outcomes of SWL technology, thus decreasing the incidence of residual fragments. SWL is reliable and safe; however, successful stone treatment strictly depends on proper patient selection. SWL should be reserved for those stones with a high likelihood of adequate fragmentation and passage. SWL should not be considered in cases in which narrowing of the urinary tract may preclude the passage and elimination of debris of adequately fragmented stones: primary and secondary ureteropelvic-junction obstruction, ureteral stricture, calyceal diverticulum/ hydrocalix, ureteroenteric strictures, or stones in proximity to obstructing large adjacent renal cysts. Moreover, SWL should not be the modality of choice to manage renal calculi larger than 2 cm if renal anomalies are present (e.g.,
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pelvic, horseshoe, malrotated kidneys) and the stone is larger than 1 cm,or for stones larger than 1 cm in transplanted kidneys.5l The majority of renal calculi larger than 2 cm should be treated with percutaneous nephrostolithotomy (PNL or PCNL), unless the calculi are thought to be soft and are in the renal pelvis or upper pole of a nondilated collecting system.51Moreover, stone location also impacts the clearance of fragments. Recent studies suggest that lower-pole renal calculi larger than l cm do not pass easily after SWL treatment.%Certain spatial anatomic factors impact stone clearance. These include the infundibulopelvic angle, infundibular length, and infundibular width.17Intrarenal anatomy, however, does not appear to have a significant impact on stone-free rates if ureteroscopic and percutaneous lithotripsy is performed to clear lower-pole stones. "Hard" stone composition (e.g. cystine, brushite, or calcium oxalate monohydrate) as well as morbid obesity, independent of the previous factors, also impact on stone-clearance rates.4,10,14.U, 25.26.3a.53 If SWL is used for the treatment of calculi that have a high chance of successful stone passage, complications and unplanned ancillary procedures are kept to a minimum. Moreover, residual fragments that result are more likely to spontaneously pass, thus achieving the desired stone-free status. METHODS TO AVOID RESIDUAL FRAGMENTS
Most residual fragments arise from one or a combination of several factors, which can be attributed to the five problems listed here: Improper selection of the surgical technique Anatomic abnormalities Stone composition Technical constraints Impatience Improper selection of the surgical technique is probably the single most important factor predicting a stone-free status versus residual fragments. One must choose among the different treatment options, selecting the therapeutic modality that best suits the individual patient and provides the optimal chance for a stonefree result with minimal morbidity, in the most cost-efficient manner. No single tech-
nique is ideal for all situations, and, therefore, improper selection of a certain procedure has a dramatic impact on stone-free status. Realistic expectations should be shared with the patient in terms of stone-free rates for a given technique, time interval and number of procedures for stone-free status, overall hospital stay, and days off work.
MANAGEMENT OF RESIDUAL STONES
It is clear that all types of residual fragments may require some sort of management, which may be medical or may involve repetition of a surgical option. There is no widespread agreement, however, regarding which residual renal calculi require surgical intervention. It is our belief that surgical treatment of postprocedural residual fragments should be used only if the primary indication for stone removal persists after the initial treatment. Therefore, further intervention should be considered in symptomatic, obstructive residual stones or in stone-associated urinarytract infection. Treatment also should be considered for asymptomatic residual stones in patients who cannot afford an episode of kidney colic (e.g., airplane pilots) or urinary-tract infection (e.g., transplant patients or individuals who are scheduled to receive prosthetic device^).^' In patients with nonobstructive, noninfectious, asymptomatic residual stones, one might consider aggressive medical therapy, with the correction of underlying metabolic disorders, to prevent stone growth or formation of new calculi. One or more metabolic abnormalities can be identified in up to 97% of stone-forming patients.40,41, 42 Therefore, one must consider the desirability of pursuing stone-free status after the initial PNL if achieving a stone-free state requires multiple subsequent invasive procedures, anesthesias, prolonged hospital stay, and increased costs. For these decisions, one also must consider that most residual fragments requiring intervention can be treated successfully by SWL if necessary, and that appropriate medical therapy can arrest their growth in most patients. With sufficient fragmentation, 80% of patients remain free of symptoms after SWL, even in the presence of residual fragment^.'^ Is it necessary to achieve a stone-free state by further treatments in this set of patients?
MANAGEMENT OF RESIDUAL STONES
Surgical Management of Residual Stones
The primary goal of today’s minimally invasive modalities for the treatment of urolithiasis is to establish a stone-free state. If removal of residual calculi is in the best interest of the patient, selection of the single best therapy or combination of therapies should be chosen to achieve the goal with minimal morbidity and the highest cost-efficiency. It has been proposed that residual fragments after PNL should be managed aggressively. In dealing with large extensively branched or otherwise complex renal calculi, some authors pursue a stone-free status by means of so-called ”sandwich therapy”: Initial PNL debulking, followed by SWL of residual fragments that are not accessible through the initial nephrostomy tracts and then second-look n e p h r o ~ c o p yMore . ~ ~ recently, it has been proposed that a nonenhanced CT scan of the abdomen be performed in the immediate postoperative period to address residual fragments, which if present can be treated with second-look flexible nephroscopy.38 The use of chemolysis in the control of residual fragments has declined dramatically over the years because of the advent of minimally invasive methods for stone treatment. It should not be removed from the urologist’s armamentarium, however, because local dissolution therapy is valuable to prevent recurrences by means of rendering the patient stone-free. The ideal chemolysis system would consist of dual nephrostomy tubes (inflow and outflow) and an indwelling ureteral catheter to guarantee passage of fragments. It is of paramount importance to know the composition of the stone to be treated, because the choice of irrigant is crucial to a successful outcome. Adherence to proper methodology in chemolysis is of utmost importance, especially in dealing with stmvite calculi, because the possibility of sepsis and death, which are related to a breach in operative technique. Particular emphasis should be placed on outflow drainage of the irrigant to keep intrapelvic pressures below 25 cm H,O.l9,46 It is clear that chemolysis reduces the rate of recurrence of calculi more than surgery alone and can have a positive impact in the management of residual fragments. In this era of managed-care medicine, however, the role of chemolyis, with its attendant in-
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creased costs and prolonged hospitalization time, is limited. Medical Management of Residual Stones
Before considering the use of metabolic therapy to manage residual fragments, one must be convinced that medical therapy is effective in preventing growth of residual stones or new stone formation.“ A number of studies have confirmed the benefits of prophylactic metabolic therapy for recurrent nephrolithiasis. One such investigation reviewed the long-term outcome of patients with calcium nephrolithiasis treated with potassium citrate.= Although this study did not address directly the fate of residual fragments with the patient on medical therapy, it clearly demonstrates the dramatic decrease of stone recurrence that can be accomplished by pharmacologically altering the stone-forming millieu of recurrent stone formers. A subsequent investigation compared the previously mentioned study on the efficacy of potassium citrate to arrest stone formation with 11 other conservative or placebo trials in order to determine if the so-called stone-clinic effect (conservative measures of high fluid intake and dietary modifications in the setting of a stone clinic) had an impact by itself in the prevention of calcium-stone recurrences.43 Annual stone formation rates were equal in the patients treated with potassium citrate before treatment and patients on conservative and placebo trials. It was determined that potassium citrate virtually halted new stone growth, with a remission rates of 96%. Conservative measures and placebo trials accounted for only a 61% remission rate. Similar conclusions were drawn when the incidence of new stone formation was analyzed in patients receiving a-mercaptopropionylglycine (MPG) for cystine nephrolithiasis. This study evaluated the long-term treatment efficacy of a-MPG on patients with cystinuria.” Treatment with a-MPG enabled patients to keep cystinuria below undersaturated levels, thus significantly decreasing the incidence of new stone formation. Cessation of stone formation was reported in 71% of the patients, and reduction of the individual stone formation rate in 94%. Taking these studies into account, a recent investigation suggested that selective medical therapy is effective in avoiding growth of
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residual fragments and inhibiting new stone formation.18This study addressed the effect of medical management on residual fragments and recurrent stone formation following SWL. More than half of their patients with postprocedural CIRFs who were not given medical therapy for their stone disease showed significant stone growth at followup. Only 16% of a similar group of patients on medical treatment, however, demonstrated increase in stone size; thus the investigators concluded that appropriate selective medical treatment can decrease the incidence of stone recurrence or growth. Facilitated Passage of Residual Stone While the Patient is Undergoing Medical Treatment
A recent study was designed to address the natural history, with and without medical treatment, of asymptomatic, post-SWL residual fragments smaller than 5 mm in size. Forty consecutive patients with sterile calcium stones and 30 with struvite stones were assigned randomly to two treatment arms: citrate therapy or conservative measures. All patients with infection stones received antibiotic treatment throughout the study. The results demonstrated that stone-free rates in calcium-stone patients that had not been treated with citrate were 21% and 32% at 6 and 12 months, respectively. Those individuals who were treated with oral citrate therapy, however, had stone-free rates of 65% and 74% at those same points. Similarly, untreated infected stone patients had stone-free rates of 27% and 40% at 6 and 12 months, and stoneclearance rates were significantly higher, 71% and 86%, if citrate therapy was used. The data also showed that citrate therapy prevented residual fragment growth or aggregation in those subjects with retained stone fragment^.^ Overall Effectiveness of Medical Therapy
The authors recommend that attempts to render a patient completely stone-free should be made to avoid inherent complications and risk for residual fragment growth. It is their policy, however, to attempt to achieve a stonefree state by means of a single "aggressive" approach (i.e., up to three percutaneous accesses, supracostal above the eleventh rib ac-
cesses, or anatrophic nephrolithotomy). The authors "metabolically" treat small residual stones that are not causing symptoms, persistent infection, or obstruction, delaying further intervention until that status changes. After a comprehensive metabolic evaluation is made, selective medical therapy is initiated to prevent growth of residual fragments or formation of new calculi. SUMMARY
Stone-free status is hghly dependent on selection of the appropriate surgical technique, which should be tailored according to the individual stone and patient parameters. Although a stone-free state is the desired outcome of surgical intervention of urolithiasis, the authors believe that the presence of noninfection, nonobstructive, asymptomatic postprocedural residual fragments can be managed metabolically in order to prevent stone growth adequately. Further surgical intervention in the case of residual fragments is warranted if the clinical indications that prompted the original surgery persist. References 1. Balaji KC, Menon M: Mechanism of stone formation. Urol Clin North Am 24:1, 1997 2. Baumgartner BR, Steinberg HV, Ambrose SS, et a1 Sonographic evaluation of renal stones treated by extracorporeal shock-wave lithotripsy. AJR Am J Rwntgenol 149:131, 1987 3. Beck EM, Riehle RA, Jr: The fate of residual fragments after extracorporeal shock wave lithotripsy monotherapy of infection stones. J Urol 145:6,1991 4. Bhatta KM, Prien EL Jr, Dretler SP: Cystine calculi: Rough and smooth: A new clinical distinction. J Urol 142:937, 1989 5. Blandy JP, Singh M: The case for a more aggressive approach to staghom stones. J Urol 115505,1976 6. Brown RD, Adams BV, Pak CYC, et al: Reliability of a single %-hour urine testing for the detection of abnormal stone-forming risk factors. In Sutton RAL, Cameron EC, Walker V, et a1 (eds): Urolithiasis. New York, Plenum, 1989, pp 553-556 7. Carr LK, DA, Honey J, Jewett MA, et al: New stone formation: A comparison of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. J Urol 1553565, 1996 8. Chaussy C, Schmiedt E, Jocham D, et a1 First clinical experience with extracorporeally induced destruction of kidney stones by shock waves. J Uroll27417,1982 9. Cicerello E, Merlo F, Fandella A, et al: Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients. J Urol 151:5, 1994
MANAGEMENT OF RESIDUAL STONES 10. Cohen NP, Whitfield HN: Mechanical testing of urinary calculi. World J Urol 11:13, 1993 11. Coughlin BF, Risius 8, Streem SB, et al: Abdominal radiograph and renal ultrasound versus excretory urography in the evaluation of asymptomatic patients after extracorporeal shock wave lithotripsy. J Urol 1421419, 1989 12. Denstedt JD, Clayman RV, Picus DD: Comparison of endoscopic and radiological residual fragment rate following percutaneous nephrolithotripsy. J Urol 145:703, 1991 13. Drach GW, Dretler SE Fair W, et al: Report of the United States cooperative study of extracorporeal shock wave lithotripsy. J Urol 1351127, 1986 14. Dretler SP: Stone fragility: A new therapeutic distinction. J Urol 139:1124, 1988 15. Eisenberger F, Bub P, Schmidt A: The fate of residual fragments after extracorporeal shock wave lithotripsy. J Endourol 6:217, 1992 16. Eisenberger F, Rassweller J, Kallert B, et al: Die Behandlung des Ausgusssteines: Strategien und Ergebnisse des kombinierten Einsatzes neuer Techniken [Treatment of staghorn calculi: Strategies and results of the combined use of new techniques]. Urologe A 28:138, 1989 17. Elbahnasy AM, Shalhav AL, Hoenig DM, et al: Lower caliceal stone clearance after shock wave lithotripsy or ureteroscopy: The impact of lower pole radiographic anatomy. J Urol 159676, 1998 18. Fine JK, Pak CY, Preminger G M Effect of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy. J Urol 15327, 1995 19. Freid RM, Smith AD: Chemolysis of urinary calculi. In Smith AD, Badlani GH, Bogley DH, et a1 (eds): Smiths Textbook of Endourology. St. Louis, Quality Medical Publishing, 1996, pp 274-297 20. Fuchs AM, Wolfson BA, Fuchs GJ: Staghom stone treatment with extracorporeal shock wave lithotripsy monotherapy: Long-term results. J Endourol5:45, 1991 21. Gleeson MJ, Shabsigh R, Griffith DP: Outcome of extracorporeal shock wave lithotripsy in patients with multiple renal calculi based on stone burden and location. J Endourol2145,1988 22. Goldwasser 8, Cohan RH, Dunnick NR, et al: Role of linear tomography in evaluation of patients with nephrolithiasis. Urology 33253, 1989 23. Gupta M, Bolton DM, Stoller ML: Etiology and management of cystine lithiasis. Urology 45:344, 1995 24. Jewett MA, Bombardier C, Caron D, et al: Potential for inter-observer and intra-observer variability in x-ray review to establish stone-free rates after lithotripsy. J Urol 147559, 1992 25. Kachel TA, Vijan SR, Dretler SP: Endourological experience with cystine calculi and a treatment algorithm. J Urol 14525, 1991 26. Klee LW, Brito CG, and Lingeman JE: The clinical implications of brushite calculi. J Urol 145:715, 1991 27. Lehtoranta K, Mankinen P, Taari K, et al: Residual stones after percutaneous nephrolithotomy: Sensitivities of different imaging methods in renal stone detection. Ann Chir Gynaecol8443, 1995 28. Lingeman JE, Lower Pole Study Group: Prospective, randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrotolithotomy for lower pole nephrolithiasis. J Urol 155:330A, 1996 29. Lingeman JE, Newman D, Mertz JH, et al: Extracor-
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poreal shock wave lithotripsy: The Methodist Hospital of Indiana experience. J Urol 1351134, 1986 30. Madsen EH: The value of tomography for the demonstration of small intra-renal calcifications. Br J Radiol 45:203, 1972 31. Middleton WD, Dodds WJ, Lawson TL, et a1 Renal calculi: Sensitivity for detection with US. Radiology 167239, 1988 32. Nakamoto T, Sagami K, Yamasaki A, et al: Long-term results of endourologic treatment of urinary calculi: Investigation of risk factors for recurrence or regrowth. J Endourol 7297, 1993 33. Newman DM, Scott JW, Lingeman JE: Two-year follow-up of patients treated with extracorporeal shock wave lithotripsy. J Endourol 2:163, 1988 34. Newman DM, Lingeman JE, Mertz JH, et al: Extracorporeal shock-wave lithotripsy. Urol Clin North Am 1463, 1987 35. Nijman RJ, Ackaert K, Scholtmeijer RJ, et al: Longterm results of extracorporeal shock wave lithotripsy in children. J Urol 142:609, 1989 36. Pak CY, Fuller C, Sakhaee K, et a1 Long-term treatment of calcium nephrolithiasis with potassium citrate. J Urol 134:11, 1985 37. Pak CY, Fuller C, Sakhaee K, et a1 Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol 136:1003, 1986 38. Pearle M, Watamul L, Mullican MA: Comparison of non-contrast helical CT and KUJj with flexible nephroscopy for detecting residual stones after percutaneous nephrostolithotomy. J Urol 159:152A, 1998 39. Pfab R, Kloiber W, Kropp W, et al: The endoscopically visible radiologically non-recognizable residual fragment. Urol Res 15327, 1987 40. Preminger GM: The metabolic evaluation of patients with recurrent nephrolithiasis: A review of comprehensive and simplified approaches. J Urol 141:760, 1989 41. Preminger GM, Harvey JA: Diagnostic considerations in nephrolithiasis. In Pak CYC (ed): Renal Stone Disease: Pathogenesis, Prevention, Treatment. Boston, Martinus Nijhoff, 1987, pp 143-164 42. Preminger GM, Pak CYC: Evaluation of patients with recurrent renal calculi. In McCullough DL (ed): Difficult Diagnoses in Urology, vol 1. Churchill Livingston, New York, 1988, pp 295-304 43. Preminger GM, Harvey JA, Pak CY Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. J Urol 134:658, 1985 44. Preminger GM, Peterson R, Peters PC, et al: The current role of medical treatment of nephrolithiasis: The impact of improved techniques of stone removal. J Urol 134:6, 1985 45. Schwartz G, Lipschitz S, Becker JA: Detection of renal calculi: The value of tomography. AJR Am J Roentgenol 143:143, 1984 46. Sheldon CA, Smith AD: Chemolysis of calculi. Urol Clin North Am 9:121, 1982 47. Streem SB, Yost A, Mascha E: Clinical implications of clinically insignificant stone fragments after extracorporeal shock wave lithotripsy. J Urol 155:1186, 1996 48. Streem SB, Geisinger MA, Risius B, et a1 Endourologic "sandwich therapy for extensive staghom calculi. J Endourol 1:253, 1987 49. Vieweg J, Teh C, Freed K, et al: Unenhanced helical computerized tomography for the evaluation of patients with acute flank pain. J Urol 160:679, 1998
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50. Wang LP, Wong HY, Griffith DP: Treatment options in struvite stones. Urol Clin North Am 24349, 1997 51. Wolf JS, Jr, Clayrnan RV Percutaneous nephrostolithotomy: What is its role in 1997? Urol Clin North Am 2443, 1997
52. Zanetti G, Montanari E, Mandressi A, et al: Longterm results of extracorporeal shock wave lithotripsy in renal stone treatment. J Endourol 5:61, 1991 53. Zhong P, Prerninger G M Mechanisms of differing stone fragility in extracorporeal shockwave lithotripsy. J Endourol8263, 1994
Address reprint requests to Glenn M. Preminger, MD Division of Urology Box 3167, Room 305 Baker House Duke University Medical Center Durham, NC 27710
e-mail: premi0016hnc.duke.edu
UROLITHIASIS
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MANAGEMENT OF RESIDUAL STONES Fernando C. Delvecchio, MD, and Glenn M. Preminger, MD
When open surgery was the standard treatment for the management of renal calculi, the presence of residual fragments suggested a failed procedure, even if those remaining fragments were small. Because residual calculi may act as a nidus for recurrent stone formation, complete stone removal was the principal goal of therapy? The introduction of shock-wave lithotripsy (SWL), however, shed a new perspective on this century-old concept, minimizing the importance of postprocedural residual fragments. Currently, most renal stones requiring treatment are managed by SWL.8 Stone-free rates following SWL, however, are highly dependent on stone location, size, number, and composition, as well as the degree of hydronephrosis and renal function of the ipsilateral renal unit.21,33 Approximately 66% to 72% of patients may be rendered stone-free if SWL is used for treatment of a wide variety of renal and ureteral lithia~is.'~, 29 Successful SWL results, however, now are defined by many reports as complete fragmentation of the original stone to fragments small enough to pass spontaneously, with no discomfort. Three months after SWL therapy, 28% to 34% of patients retain stone particles, and post-SWL fragments may take as long as 30 months to pass spontaneously."jConsequently, the principles of SWL therapy have changed com-
pletely the dogmas of open surgery, in which the aim was to render the patient completely stone-free at the completion of the operative procedure.
CLINICALLY INSIGNIFICANT RESIDUAL FRAGMENTS
In this age of SWL and other minimally invasive endoscopic stone-removal techniques, the significance and fate of residual fragments after treatment remains unclear. Clinically insign$cant residual fragment (CIRF) was a new term rapidly added to urologists' vocabulary with the advent of SWL, to address such posttreatment stones. Despite the widespread use of this term, there is no consensus regarding the maximum size or characteristics that stone fragments should have, if any, to be insignificant, avoiding growth, becoming symptomatic, or requiring interent ti on.^^ CIRFs usually are SWL residual fragments that are smaller than 4 mm (or sometimes 5 mm), asymptomatic, nonobstructive, noninfectious, and associated with sterile urine. By extension, this term also defines stones of similar characteristics left behind after percutaneous nephrostolithotomy or ureteroscopic procedures.
From the Division of Urology, Department of Surgery (FCD, GMF),and The Comprehensive Kidney Stone Center (GMP),Duke University Medical Center, Durham, North Carolina UROLOGIC CLINICS OF NORTH AMERICA
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DIAGNOSIS OF RESIDUAL FRAGMENTS
The most accurate diagnostic test to address the presence of residual fragments is probably nephroscopy, because some radiologic imaging studies may overestimate postprocedural stone-free rates.'2,39 Nephroscopy, however, for obvious reasons is routinely feasible postoperatively only in patients who recently have undergone a percutaneous nephrostolithotomy and still have a nephrostomy tube in place. The degree of overestimation of stone-free rates varies according to the different sensitivities of the individual imaging modalities. The initial report that compared endoscopic and radiological evaluation of residual fragment rates following percutaneous nephrolithotripsy and SWL demonstrated that plain abdominal radiographs and renal tomography overestimated stone-free rates by 35% and 17%, respectively, compared with flexible nephroscopy.'2 Moreover, studies have reported interobserver and intraobserver variability in radiographic review of residual fragment^?^ Plain abdominal films alone are the most difficult to interpret, resulting in the highest uncertainty (and hence observer variability) about 24 This fact the presence of residual results from the superimposition of bowel gas, feces, and soft-tissue calcifications. Obesity and the presence of faintly radioopaque nephrolithiasis also contribute to the misdiagnosis. Some reports have suggested that linear tomograms detect 13% to 46% more stones than originally reported by plain films.22,30, 45 Another study has documented that there is significantly less interobserver variability in the identification of stones with tomography than with plain radiographyz4 Reading plain abdominal films and tomograms together reduces even more inter- and intraobserver variability, and these differences are usually minor. Several reports have addressed the sensitivity of ultrasound in the detection of urolithiasis to be between 65% and %%?, 31 The advantage of ultrasound relies on the fact that all stones, independent of their composition, present an acoustic-impedance mismatch with the surrounding tissues, and attenuate sound to a greater degree. For these reasons, radiolucent and radioopaque stones appear as echogenic foci with an acoustic shadow behind. The diagnostic reliability of ultra-
sound falls dramatically, however, in scanning for stones in the ureter. Moreover, ultrasound is inadequate in quantifying the stone burden and generally does not permit differentiation of intact stones from fragmented ones.31Therefore, sonography should be used only as a complement to other conventional radiographic imaging studies and not on its own merits. In this setting, a combination of abdominal radiography and renal ultrasonography has been proven to be as good or better than intravenous urography in identifying residual stone fragments and intrarenal and perirenal abnormalities in a set of asymptomatic patients 1 month after SWL." The sensitivity of CT has been shown to be superior to plain radiography ( P < 0.05), linear tomography ( P < .05) and ultrasonography (P < .01)in detecting postprocedural residual stones.27Noncontrast spiral CT was demonstrated to be superior to plain radiography combined with sonography in determining size and location of renal and ureteric calculi.49Noncontrast spiral CT also was shown to have superior sensitivity and equal specificity to intravenous urography in detecting renal stones and demonstrates equal sensitivity in the detection of ureteral dilation. Compared with intravenous urography, CT can detect stones of various compositions adequately, and both studies are comparable in terms of overall costs and ionizing radiation delivered. CT and intravenous urography, however, can be upwards of three times as expensive as plain abdominal films or tomography. IMPORTANCE OF RESIDUAL FRAGMENTS
Residual fragments may be important for a variety of reasons: They may act as a nidus for recurrent stone growth, they can become dislodged acutely and cause significant obstruction with pain and infection, or they might be the source of persistent infection. After stone fragmentation or removal by any modality, the underlying metabolic abnormalities for recurrent stone formation persist.6 Supersaturation of the urine with stoneforming salts or lack of stone inhibitors may accelerate the growth of residual fragments, irrespective of their size, and promote new stone recurrence. Residual calculi may act as a nidus for stone growth by heterogeneous nucleation.
MANAGEMENT OF RESIDUAL STONES
This is a process in which particulate matter in the urine, such as other crystals, may act as nucleating foci. The saturation needed for heterogeneous nucleation is much less than for homogeneous nucleation. Crystallization can occur at lower chemical saturations than required for the formation of the initial stone nucleus.’ Crystal aggregation also may enhance the growth of pre-existing fragments. Several studies have stressed the long-term recurrence rates posed by postprocedural residual calculi because of the previously mentioned reasons. These investigations report stone-recurrence rates of 10% to 15% if the patient was rendered stone-free, in contrast to a 50% to 80% incidence of stone growth or new stone formation if residual stones were present after the SWL procedure.” 20, 32, 52 A recent report suggests that patients rendered stone-free by SWL demonstrate a higher stone-recurrence rate than a similar group of patients treated by percutaneous nephrolithotomy, without ultrasonic fragmentation? This study documents a significantly higher number of new stone recurrence in lower and midcalyces (compared with baseline location) after SWL than after percutaneous nephrolithotripsy. The results suggest that higher recurrence rates after SWL may be caused by microscopic sand particles migrating to dependent calyces and acting as a niduses for new stone formation. SWL, by dramatically increasing the surface area of the original stone, may favor new stone growth through heterogeneous nucleation, and crystal aggregation by exposing more stone area to the lithogenic environment. A recent prospective study followed 160 patients with 4-mm or smaller asymptomatic calcium oxalate or calcium phosphate stone fragments after SWL for a mean of 23 months to stone-free status, censorship, or intervention, in order to address the clinical implications of CIRFs. Stone-free status or a decreased, stable, or increased amount of residual stone occurred in 23.8%, 16.3%, 41.9%, and 18.1% of the 160 patients, respectively. Kaplan-Meier estimates of the probability of these outcomes at 5 years were 0.36 for spontaneously achieving a stone-free status, 0.53 for spontaneously achieving a stonefree or decreased stone status, and 0.80 for achievement of stone-free, decreased, or stable At follow up, however, 43.1% of patients had developed significant symptomatic episodes or needed intervention, and Kaplan-Meier estimates predicted this possi-
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bility to be around 70% if small residual fragments were left and follow-up was 5 years after SWL. Even investigators who believe in the existence of CIRFs do not consider retained calculi of struvite to be insignificant, because the urea-splitting bacteria necessary for the formation of these stones may persist in the remaining fragments, thus promoting a cycle of persistent infection and accelerated growth. In vitro studies demonstrate that crystal production by Pro teus rnirabdis, the commonest causative organism, can occur in only 4 Struvite stones tend to recur in 10% of cases after complete stone removal and in 85% of patients if stone remnants are left behind.’ Therefore, there is clear evidence in the literature that untreated postprocedural residual fragments pose a significant risk for stone recurrence or new stone growth. The authors consider CIRF to be a misnomer that leads to the acce tance of treatment failures and minimizes e importance of untreated stones within the urinary system.
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INCIDENCE AND CAUSE OF RESIDUAL STONES
The reported incidence of residual stones varies according to the treatment modality used. Several factors impact the resence of postprocedural residual stones. ey include stone composition, size, and location, as well as anatomy of the urinary tract. Clinical experience accumulated throughout the years has been able to idenhfy stone and anatomic characteristics that predict treatment outcomes of SWL technology, thus decreasing the incidence of residual fragments. SWL is reliable and safe; however, successful stone treatment strictly depends on proper patient selection. SWL should be reserved for those stones with a high likelihood of adequate fragmentation and passage. SWL should not be considered in cases in which narrowing of the urinary tract may preclude the passage and elimination of debris of adequately fragmented stones: primary and secondary ureteropelvic-junction obstruction, ureteral stricture, calyceal diverticulum/ hydrocalix, ureteroenteric strictures, or stones in proximity to obstructing large adjacent renal cysts. Moreover, SWL should not be the modality of choice to manage renal calculi larger than 2 cm if renal anomalies are present (e.g.,
TR
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pelvic, horseshoe, malrotated kidneys) and the stone is larger than 1 cm,or for stones larger than 1 cm in transplanted kidneys.5l The majority of renal calculi larger than 2 cm should be treated with percutaneous nephrostolithotomy (PNL or PCNL), unless the calculi are thought to be soft and are in the renal pelvis or upper pole of a nondilated collecting system.51Moreover, stone location also impacts the clearance of fragments. Recent studies suggest that lower-pole renal calculi larger than l cm do not pass easily after SWL treatment.%Certain spatial anatomic factors impact stone clearance. These include the infundibulopelvic angle, infundibular length, and infundibular width.17Intrarenal anatomy, however, does not appear to have a significant impact on stone-free rates if ureteroscopic and percutaneous lithotripsy is performed to clear lower-pole stones. "Hard" stone composition (e.g. cystine, brushite, or calcium oxalate monohydrate) as well as morbid obesity, independent of the previous factors, also impact on stone-clearance rates.4,10,14.U, 25.26.3a.53 If SWL is used for the treatment of calculi that have a high chance of successful stone passage, complications and unplanned ancillary procedures are kept to a minimum. Moreover, residual fragments that result are more likely to spontaneously pass, thus achieving the desired stone-free status. METHODS TO AVOID RESIDUAL FRAGMENTS
Most residual fragments arise from one or a combination of several factors, which can be attributed to the five problems listed here: Improper selection of the surgical technique Anatomic abnormalities Stone composition Technical constraints Impatience Improper selection of the surgical technique is probably the single most important factor predicting a stone-free status versus residual fragments. One must choose among the different treatment options, selecting the therapeutic modality that best suits the individual patient and provides the optimal chance for a stonefree result with minimal morbidity, in the most cost-efficient manner. No single tech-
nique is ideal for all situations, and, therefore, improper selection of a certain procedure has a dramatic impact on stone-free status. Realistic expectations should be shared with the patient in terms of stone-free rates for a given technique, time interval and number of procedures for stone-free status, overall hospital stay, and days off work.
MANAGEMENT OF RESIDUAL STONES
It is clear that all types of residual fragments may require some sort of management, which may be medical or may involve repetition of a surgical option. There is no widespread agreement, however, regarding which residual renal calculi require surgical intervention. It is our belief that surgical treatment of postprocedural residual fragments should be used only if the primary indication for stone removal persists after the initial treatment. Therefore, further intervention should be considered in symptomatic, obstructive residual stones or in stone-associated urinarytract infection. Treatment also should be considered for asymptomatic residual stones in patients who cannot afford an episode of kidney colic (e.g., airplane pilots) or urinary-tract infection (e.g., transplant patients or individuals who are scheduled to receive prosthetic device^).^' In patients with nonobstructive, noninfectious, asymptomatic residual stones, one might consider aggressive medical therapy, with the correction of underlying metabolic disorders, to prevent stone growth or formation of new calculi. One or more metabolic abnormalities can be identified in up to 97% of stone-forming patients.40,41, 42 Therefore, one must consider the desirability of pursuing stone-free status after the initial PNL if achieving a stone-free state requires multiple subsequent invasive procedures, anesthesias, prolonged hospital stay, and increased costs. For these decisions, one also must consider that most residual fragments requiring intervention can be treated successfully by SWL if necessary, and that appropriate medical therapy can arrest their growth in most patients. With sufficient fragmentation, 80% of patients remain free of symptoms after SWL, even in the presence of residual fragment^.'^ Is it necessary to achieve a stone-free state by further treatments in this set of patients?
MANAGEMENT OF RESIDUAL STONES
Surgical Management of Residual Stones
The primary goal of today’s minimally invasive modalities for the treatment of urolithiasis is to establish a stone-free state. If removal of residual calculi is in the best interest of the patient, selection of the single best therapy or combination of therapies should be chosen to achieve the goal with minimal morbidity and the highest cost-efficiency. It has been proposed that residual fragments after PNL should be managed aggressively. In dealing with large extensively branched or otherwise complex renal calculi, some authors pursue a stone-free status by means of so-called ”sandwich therapy”: Initial PNL debulking, followed by SWL of residual fragments that are not accessible through the initial nephrostomy tracts and then second-look n e p h r o ~ c o p yMore . ~ ~ recently, it has been proposed that a nonenhanced CT scan of the abdomen be performed in the immediate postoperative period to address residual fragments, which if present can be treated with second-look flexible nephroscopy.38 The use of chemolysis in the control of residual fragments has declined dramatically over the years because of the advent of minimally invasive methods for stone treatment. It should not be removed from the urologist’s armamentarium, however, because local dissolution therapy is valuable to prevent recurrences by means of rendering the patient stone-free. The ideal chemolysis system would consist of dual nephrostomy tubes (inflow and outflow) and an indwelling ureteral catheter to guarantee passage of fragments. It is of paramount importance to know the composition of the stone to be treated, because the choice of irrigant is crucial to a successful outcome. Adherence to proper methodology in chemolysis is of utmost importance, especially in dealing with stmvite calculi, because the possibility of sepsis and death, which are related to a breach in operative technique. Particular emphasis should be placed on outflow drainage of the irrigant to keep intrapelvic pressures below 25 cm H,O.l9,46 It is clear that chemolysis reduces the rate of recurrence of calculi more than surgery alone and can have a positive impact in the management of residual fragments. In this era of managed-care medicine, however, the role of chemolyis, with its attendant in-
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creased costs and prolonged hospitalization time, is limited. Medical Management of Residual Stones
Before considering the use of metabolic therapy to manage residual fragments, one must be convinced that medical therapy is effective in preventing growth of residual stones or new stone formation.“ A number of studies have confirmed the benefits of prophylactic metabolic therapy for recurrent nephrolithiasis. One such investigation reviewed the long-term outcome of patients with calcium nephrolithiasis treated with potassium citrate.= Although this study did not address directly the fate of residual fragments with the patient on medical therapy, it clearly demonstrates the dramatic decrease of stone recurrence that can be accomplished by pharmacologically altering the stone-forming millieu of recurrent stone formers. A subsequent investigation compared the previously mentioned study on the efficacy of potassium citrate to arrest stone formation with 11 other conservative or placebo trials in order to determine if the so-called stone-clinic effect (conservative measures of high fluid intake and dietary modifications in the setting of a stone clinic) had an impact by itself in the prevention of calcium-stone recurrences.43 Annual stone formation rates were equal in the patients treated with potassium citrate before treatment and patients on conservative and placebo trials. It was determined that potassium citrate virtually halted new stone growth, with a remission rates of 96%. Conservative measures and placebo trials accounted for only a 61% remission rate. Similar conclusions were drawn when the incidence of new stone formation was analyzed in patients receiving a-mercaptopropionylglycine (MPG) for cystine nephrolithiasis. This study evaluated the long-term treatment efficacy of a-MPG on patients with cystinuria.” Treatment with a-MPG enabled patients to keep cystinuria below undersaturated levels, thus significantly decreasing the incidence of new stone formation. Cessation of stone formation was reported in 71% of the patients, and reduction of the individual stone formation rate in 94%. Taking these studies into account, a recent investigation suggested that selective medical therapy is effective in avoiding growth of
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residual fragments and inhibiting new stone formation.18This study addressed the effect of medical management on residual fragments and recurrent stone formation following SWL. More than half of their patients with postprocedural CIRFs who were not given medical therapy for their stone disease showed significant stone growth at followup. Only 16% of a similar group of patients on medical treatment, however, demonstrated increase in stone size; thus the investigators concluded that appropriate selective medical treatment can decrease the incidence of stone recurrence or growth. Facilitated Passage of Residual Stone While the Patient is Undergoing Medical Treatment
A recent study was designed to address the natural history, with and without medical treatment, of asymptomatic, post-SWL residual fragments smaller than 5 mm in size. Forty consecutive patients with sterile calcium stones and 30 with struvite stones were assigned randomly to two treatment arms: citrate therapy or conservative measures. All patients with infection stones received antibiotic treatment throughout the study. The results demonstrated that stone-free rates in calcium-stone patients that had not been treated with citrate were 21% and 32% at 6 and 12 months, respectively. Those individuals who were treated with oral citrate therapy, however, had stone-free rates of 65% and 74% at those same points. Similarly, untreated infected stone patients had stone-free rates of 27% and 40% at 6 and 12 months, and stoneclearance rates were significantly higher, 71% and 86%, if citrate therapy was used. The data also showed that citrate therapy prevented residual fragment growth or aggregation in those subjects with retained stone fragment^.^ Overall Effectiveness of Medical Therapy
The authors recommend that attempts to render a patient completely stone-free should be made to avoid inherent complications and risk for residual fragment growth. It is their policy, however, to attempt to achieve a stonefree state by means of a single "aggressive" approach (i.e., up to three percutaneous accesses, supracostal above the eleventh rib ac-
cesses, or anatrophic nephrolithotomy). The authors "metabolically" treat small residual stones that are not causing symptoms, persistent infection, or obstruction, delaying further intervention until that status changes. After a comprehensive metabolic evaluation is made, selective medical therapy is initiated to prevent growth of residual fragments or formation of new calculi. SUMMARY
Stone-free status is hghly dependent on selection of the appropriate surgical technique, which should be tailored according to the individual stone and patient parameters. Although a stone-free state is the desired outcome of surgical intervention of urolithiasis, the authors believe that the presence of noninfection, nonobstructive, asymptomatic postprocedural residual fragments can be managed metabolically in order to prevent stone growth adequately. Further surgical intervention in the case of residual fragments is warranted if the clinical indications that prompted the original surgery persist. References 1. Balaji KC, Menon M: Mechanism of stone formation. Urol Clin North Am 24:1, 1997 2. Baumgartner BR, Steinberg HV, Ambrose SS, et a1 Sonographic evaluation of renal stones treated by extracorporeal shock-wave lithotripsy. AJR Am J Rwntgenol 149:131, 1987 3. Beck EM, Riehle RA, Jr: The fate of residual fragments after extracorporeal shock wave lithotripsy monotherapy of infection stones. J Urol 145:6,1991 4. Bhatta KM, Prien EL Jr, Dretler SP: Cystine calculi: Rough and smooth: A new clinical distinction. J Urol 142:937, 1989 5. Blandy JP, Singh M: The case for a more aggressive approach to staghom stones. J Urol 115505,1976 6. Brown RD, Adams BV, Pak CYC, et al: Reliability of a single %-hour urine testing for the detection of abnormal stone-forming risk factors. In Sutton RAL, Cameron EC, Walker V, et a1 (eds): Urolithiasis. New York, Plenum, 1989, pp 553-556 7. Carr LK, DA, Honey J, Jewett MA, et al: New stone formation: A comparison of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. J Urol 1553565, 1996 8. Chaussy C, Schmiedt E, Jocham D, et a1 First clinical experience with extracorporeally induced destruction of kidney stones by shock waves. J Uroll27417,1982 9. Cicerello E, Merlo F, Fandella A, et al: Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients. J Urol 151:5, 1994
MANAGEMENT OF RESIDUAL STONES 10. Cohen NP, Whitfield HN: Mechanical testing of urinary calculi. World J Urol 11:13, 1993 11. Coughlin BF, Risius 8, Streem SB, et al: Abdominal radiograph and renal ultrasound versus excretory urography in the evaluation of asymptomatic patients after extracorporeal shock wave lithotripsy. J Urol 1421419, 1989 12. Denstedt JD, Clayman RV, Picus DD: Comparison of endoscopic and radiological residual fragment rate following percutaneous nephrolithotripsy. J Urol 145:703, 1991 13. Drach GW, Dretler SE Fair W, et al: Report of the United States cooperative study of extracorporeal shock wave lithotripsy. J Urol 1351127, 1986 14. Dretler SP: Stone fragility: A new therapeutic distinction. J Urol 139:1124, 1988 15. Eisenberger F, Bub P, Schmidt A: The fate of residual fragments after extracorporeal shock wave lithotripsy. J Endourol 6:217, 1992 16. Eisenberger F, Rassweller J, Kallert B, et al: Die Behandlung des Ausgusssteines: Strategien und Ergebnisse des kombinierten Einsatzes neuer Techniken [Treatment of staghorn calculi: Strategies and results of the combined use of new techniques]. Urologe A 28:138, 1989 17. Elbahnasy AM, Shalhav AL, Hoenig DM, et al: Lower caliceal stone clearance after shock wave lithotripsy or ureteroscopy: The impact of lower pole radiographic anatomy. J Urol 159676, 1998 18. Fine JK, Pak CY, Preminger G M Effect of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy. J Urol 15327, 1995 19. Freid RM, Smith AD: Chemolysis of urinary calculi. In Smith AD, Badlani GH, Bogley DH, et a1 (eds): Smiths Textbook of Endourology. St. Louis, Quality Medical Publishing, 1996, pp 274-297 20. Fuchs AM, Wolfson BA, Fuchs GJ: Staghom stone treatment with extracorporeal shock wave lithotripsy monotherapy: Long-term results. J Endourol5:45, 1991 21. Gleeson MJ, Shabsigh R, Griffith DP: Outcome of extracorporeal shock wave lithotripsy in patients with multiple renal calculi based on stone burden and location. J Endourol2145,1988 22. Goldwasser 8, Cohan RH, Dunnick NR, et al: Role of linear tomography in evaluation of patients with nephrolithiasis. Urology 33253, 1989 23. Gupta M, Bolton DM, Stoller ML: Etiology and management of cystine lithiasis. Urology 45:344, 1995 24. Jewett MA, Bombardier C, Caron D, et al: Potential for inter-observer and intra-observer variability in x-ray review to establish stone-free rates after lithotripsy. J Urol 147559, 1992 25. Kachel TA, Vijan SR, Dretler SP: Endourological experience with cystine calculi and a treatment algorithm. J Urol 14525, 1991 26. Klee LW, Brito CG, and Lingeman JE: The clinical implications of brushite calculi. J Urol 145:715, 1991 27. Lehtoranta K, Mankinen P, Taari K, et al: Residual stones after percutaneous nephrolithotomy: Sensitivities of different imaging methods in renal stone detection. Ann Chir Gynaecol8443, 1995 28. Lingeman JE, Lower Pole Study Group: Prospective, randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrotolithotomy for lower pole nephrolithiasis. J Urol 155:330A, 1996 29. Lingeman JE, Newman D, Mertz JH, et al: Extracor-
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poreal shock wave lithotripsy: The Methodist Hospital of Indiana experience. J Urol 1351134, 1986 30. Madsen EH: The value of tomography for the demonstration of small intra-renal calcifications. Br J Radiol 45:203, 1972 31. Middleton WD, Dodds WJ, Lawson TL, et a1 Renal calculi: Sensitivity for detection with US. Radiology 167239, 1988 32. Nakamoto T, Sagami K, Yamasaki A, et al: Long-term results of endourologic treatment of urinary calculi: Investigation of risk factors for recurrence or regrowth. J Endourol 7297, 1993 33. Newman DM, Scott JW, Lingeman JE: Two-year follow-up of patients treated with extracorporeal shock wave lithotripsy. J Endourol 2:163, 1988 34. Newman DM, Lingeman JE, Mertz JH, et al: Extracorporeal shock-wave lithotripsy. Urol Clin North Am 1463, 1987 35. Nijman RJ, Ackaert K, Scholtmeijer RJ, et al: Longterm results of extracorporeal shock wave lithotripsy in children. J Urol 142:609, 1989 36. Pak CY, Fuller C, Sakhaee K, et a1 Long-term treatment of calcium nephrolithiasis with potassium citrate. J Urol 134:11, 1985 37. Pak CY, Fuller C, Sakhaee K, et a1 Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol 136:1003, 1986 38. Pearle M, Watamul L, Mullican MA: Comparison of non-contrast helical CT and KUJj with flexible nephroscopy for detecting residual stones after percutaneous nephrostolithotomy. J Urol 159:152A, 1998 39. Pfab R, Kloiber W, Kropp W, et al: The endoscopically visible radiologically non-recognizable residual fragment. Urol Res 15327, 1987 40. Preminger GM: The metabolic evaluation of patients with recurrent nephrolithiasis: A review of comprehensive and simplified approaches. J Urol 141:760, 1989 41. Preminger GM, Harvey JA: Diagnostic considerations in nephrolithiasis. In Pak CYC (ed): Renal Stone Disease: Pathogenesis, Prevention, Treatment. Boston, Martinus Nijhoff, 1987, pp 143-164 42. Preminger GM, Pak CYC: Evaluation of patients with recurrent renal calculi. In McCullough DL (ed): Difficult Diagnoses in Urology, vol 1. Churchill Livingston, New York, 1988, pp 295-304 43. Preminger GM, Harvey JA, Pak CY Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. J Urol 134:658, 1985 44. Preminger GM, Peterson R, Peters PC, et al: The current role of medical treatment of nephrolithiasis: The impact of improved techniques of stone removal. J Urol 134:6, 1985 45. Schwartz G, Lipschitz S, Becker JA: Detection of renal calculi: The value of tomography. AJR Am J Roentgenol 143:143, 1984 46. Sheldon CA, Smith AD: Chemolysis of calculi. Urol Clin North Am 9:121, 1982 47. Streem SB, Yost A, Mascha E: Clinical implications of clinically insignificant stone fragments after extracorporeal shock wave lithotripsy. J Urol 155:1186, 1996 48. Streem SB, Geisinger MA, Risius B, et a1 Endourologic "sandwich therapy for extensive staghom calculi. J Endourol 1:253, 1987 49. Vieweg J, Teh C, Freed K, et al: Unenhanced helical computerized tomography for the evaluation of patients with acute flank pain. J Urol 160:679, 1998
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50. Wang LP, Wong HY, Griffith DP: Treatment options in struvite stones. Urol Clin North Am 24349, 1997 51. Wolf JS, Jr, Clayrnan RV Percutaneous nephrostolithotomy: What is its role in 1997? Urol Clin North Am 2443, 1997
52. Zanetti G, Montanari E, Mandressi A, et al: Longterm results of extracorporeal shock wave lithotripsy in renal stone treatment. J Endourol 5:61, 1991 53. Zhong P, Prerninger G M Mechanisms of differing stone fragility in extracorporeal shockwave lithotripsy. J Endourol8263, 1994
Address reprint requests to Glenn M. Preminger, MD Division of Urology Box 3167, Room 305 Baker House Duke University Medical Center Durham, NC 27710
e-mail: premi0016hnc.duke.edu