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Post-ESWL, clinically insignificant residual stones: reality or myth?
ADULT UROLOGY
POST-ESWL, CLINICALLY INSIGNIFICANT RESIDUAL STONES: REALITY OR MYTH? ANURAG KHAITAN, NARMADA P. GUPTA, ASHOK K. HEMAL, P. N. DOGRA, AMLESH SETH, MONISH ARON
AND
ABSTRACT Objectives. To assess the significance of asymptomatic residual stone fragments of less than 4 mm (clinically insignificant residual fragments [CIRFs]) after extracorporeal shock wave lithotripsy (ESWL). Methods. Eighty-one patients were followed up for 6 to 60 months (mean 15) after ESWL to determine the fate of the CIRFs. Results. Of the 81 patients, 6 were lost to follow-up, leaving 75 patients. During follow-up, fragments passed spontaneously in 18 patients, remained stable in 13 patients, and became clinically significant in 44 patients who developed one or more complications. For the latter patients, repeated ESWL was done in 16, percutaneous nephrolithotomy in 3, and ureteroscopic stone removal in 4 patients. The remaining 21 patients were treated conservatively with analgesics. We found that 53% of the CIRFs located in the pelvis passed spontaneously, and most of the CIRFs in caliceal location became clinically significant. Also, as the stone burden and number of stone fragments increased, the risk of CIRFs becoming clinically significant increased. The outcome was the same whether a metabolic abnormality was present or not, provided the patient received appropriate treatment. The clearance rate was highest in the first 6 months. Finally, as the duration of follow-up increased, the rate of complications increased. Conclusions. Patients with residual stones after ESWL require close follow-up and timely adjuvant therapy. As the number and size of residual fragments increased, the risk of complications increased. A pelvic location was a favorable factor for spontaneous passage. Metabolic defects, if treated adequately, did not increase the regrowth rate. Although the complete clearance rate of CIRFs with repeated ESWL was lower than for the operative interventions, most patients improved with this modality. UROLOGY 59: 20–24, 2002. © 2002, Elsevier Science Inc.
T
he emergence of extracorporeal shock wave lithotripsy (ESWL) as the treatment of choice for most patients with upper tract calculi has brought a new concept of clinically insignificant residual fragments (CIRFs).1,2 The clearance of these fragments is not immediate, and as many as 85% of patients have been reported to have residual fragments in the kidney a few days after ESWL.3 Fragments of more than 5 mm are generally considered a failure of the ESWL session and require treatment.4 The term CIRFs is controversial, because no consensus has been reached regarding the size for its definition or interval after From the Department of Urology, All India Institute of Medical Sciences, New Delhi, India Reprint requests: Narmada P. Gupta, M.D., Department of Urology, All India Institute of Medical Sciences, New Delhi 110029, India Submitted: June 20, 2001, accepted (with revisions): September 7, 2001
20
© 2002, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
ESWL to evaluate its presence. Also, the choice of imaging modality and the treatment required are controversial. These fragments have the potential to cause ureteral obstruction and are important risk factors for stone growth and recurrence. We carried out a prospective study to analyze the fate of such fragments and the intervention required for such a situation. MATERIAL AND METHODS In the past 5 years, 1250 patients with renal stones were treated with ESWL at our center. Of these, complete clearance was achieved in 830 cases, another modality of treatment was required in 130 failed cases, and 209 patients were lost to follow-up. We prospectively followed up the remaining 81 patients who had CIRFs 3 months after the last session of ESWL. Six patients were excluded because of inadequate follow-up data, and the data of the remaining 75 were analyzed. CIRFs were defined as post-ESWL, nonobstructive, noninfectious, asymptomatic (absence of pain, hematuria, and pyuria), residual fragments 4 mm or less in size.5 All patients were 0090-4295/02/$22.00 PII S0090-4295(01)01494-7
TABLE I. Patient characteristics Total patients (n) Lost to follow-up (n) Males/females (n) Right/left (n) Average age (yr) Spontaneous clearance (n) Stable (n) Complications (becoming clinically significant) (n)
81 6 57/18 32/43 36 (range 9–60) 18 13 44
TABLE II. Complications in patients with CIRFs on follow-up Complication
n
Regrowth Pain Recurrent urinary tract infections Increased number of stones Ureteric obstruction Hematuria Hypertension Lower pole nonfunctioning kidney
41 35 5 4 4 2 1 2
KEY: CIRFs ⫽ clinically insignificant residual fragments.
treated using Siemen’s Lithostar Plus. The average size of the CIRFs was assessed in two dimensions for their largest diameter. The stone burden was the sum product of these two diameters for all fragments. Patients were divided into three groups, depending on the stone burden: 10 mm2 or less, 11 to 20 mm2, and greater than 20 mm2. Stone analysis was done by the x-ray diffraction method. The follow-up period ranged from 6 to 60 months (mean 15). The follow-up was done at 3-month intervals with clinical examinations, urinalysis and culture, renal function tests, and abdominal radiography. The location of fragments in the renal pelvis, inferior, middle, or superior calix, and multiple calices was recorded as determined by intravenous urography or ultrasonography. A metabolic evaluation was done on all patients and included urine pH, stone analysis, serum calcium, phosphorus, and uric acid, and 24-hour urinary calcium, phosphorus, uric acid, creatinine, and electrolytes. For patients diagnosed with hyperuricemia, increasing the fluid intake to maintain urine output of more than 2 L/day, a low purine diet, alkalinization, and allopurinol were advised. For those with hypercalcemia, fluid therapy, restricted dairy products and salt intake, alkalinization, and thiazides were used. They were reviewed for adequate control on follow-up visits. Those developing any complication during follow-up received appropriate treatment with repeated ESWL, percutaneous nephrolithotomy, ureteroscopy, or, conservatively, with analgesics.
RESULTS The patient characteristics are shown in Table I. The most common site for CIRFs was the inferior calix followed by the renal pelvis. The other sites were relatively uncommon. Most of the patients with CIRFs had one stone (n ⫽ 39) followed by two, three, and more than three fragments in 15, 4, and 17 patients, respectively. The stone burden was less than 10 mm2, 10 to 20 mm2, and larger than 20 mm2 in 49, 19, and 12 patients, respectively. Stone analysis revealed that 70 patients had calcium oxalate, 4 had uric acid, and 1 had calcium phosphate stones. This stone composition was not significantly different from that in those with complete clearance. During follow-up, fragments passed spontaneously in 18 patients, remained stable in 13, and became clinically significant in 44 patients, who developed one or more complications (Table II). For those who developed complications, repeated ESWL was required in 16 patients, percutaneous nephrolithotomy in 3, and ureteroscopic stone removal in 4. UROLOGY 59 (1), 2002
TABLE III. Interventions conducted for complications and their outcome Outcome (n) Procedure ESWL PCNL URS Partial nephrectomy
Patients (n)
Cleared
Residual (<4 mm)
16 3 4 1
3 3 4 1
13 0 0 0
KEY: ESWL ⫽ extracorporeal shock wave lithotripsy; PCNL ⫽ percutaneous nephrolithotomy; URS ⫽ ureteroscopy.
The remaining 21 patients were treated conservatively with analgesics (Table III). We found that 53% of the CIRFs located in the renal pelvis passed spontaneously, and most CIRFs in a caliceal location became clinically significant (Table IV). Also, as the stone burden increased, the risk of the CIRFs becoming clinically significant increased; similar findings were observed with an increasing number of stone fragments (Table IV). Eighteen patients had a metabolic abnormality. Of these, 14 had hyperuricemia and 4 had hypercalciuria; all received medical therapy. The outcome was the same whether a metabolic abnormality was present or not, provided the patient received appropriate treatment. In patients who required repeated ESWL, 13 of 16 again developed residual fragments of 4 mm or less, and 1 of the 13 later required ureteroscopic stone removal. Thus, stone clearance was achieved in only 3 patients. This was in contrast to those treated with operative intervention, who all achieved complete clearance (Table III). The clearance rate was highest in the first 6 months but did continue for 12 months in some cases. As the duration of follow-up increased, the rate of complications increased. COMMENT Residual fragments represent a common and still controversial problem of ESWL. Although effica21
TABLE IV. Correlation of various prognostic factors with outcome Total Patients (n) Prognostic factor Male Female Right Left Stone burden (mm2) ⬍10 11–20 ⬎20 Stone number 1 2 3 ⬎3 Stone site Pelvic Inferior calix Middle calix Superior calix Multiple calices Metabolic defect Present Absent
Cleared (%) (24.5) (22) (22) (25.6)
Stable (%)
Clinically Significant (%)
8 5 7 6
35 9 18 26
57 18 32 43
14 4 7 11
49 19 12
16 (32.7) 2 (10.5) 2 (16.7)
9 (18.3) 3 (15.8) 1 (8.3)
24 (49) 14 (73.7) 9 (75)
S
39 15 4 17
13 3 0 2
7 3 1 2
(18) (20) (25) (11.8)
19 9 3 13
(48.7) (60) (75) (76.4)
S
6 26 6 2 4
(40) (59) (100) (67) (57.5)
S
(33.3) (20) (0) (11.8)
(14) (28) (22) (14)
15 44 6 3 7
8 (33.3) 9 (20.5) 0 1 (33) 0
1 (6.7) 9 (20.5) 0 0 3 (42.5)
18 57
6 (33.3) 12 (21.1)
2 (11.1) 11 (19.3)
(61.5) (50) (56) (60.4)
Statistical Significance
10 (55.6) 34 (59.6)
NS NS
NS
KEY: NS ⫽ not significant; S ⫽ significant.
cious fragmentation of stones with ESWL into fragments less than 5 mm has been described in 85%3 to 96%1 of cases, residual fragments are still present in 24% to 36% of cases 3 months after ESWL treatment.1,3,5,6 Asymptomatic fragments less than 5 mm and not associated with infection were initially defined as CIRFs, but many investigators have reported regrowth of these fragments in 21% to 70% of cases.2,5–9 In our study, regrowth was seen in 59% of cases, in contrast to the 2% growth rate of residual fragments at a mean follow-up of 2.5 years in the series of Buchholz et al.10 In 24% of patients, stone fragments passed spontaneously. This was comparable with other reports,2,4 but was lower than the 87% clearance rate in a few series.10 The difference may be because in the latter report, patients were included at 1 month after ESWL, not 3 months as in our study. The possibility of CIRFs becoming clinically significant increased as their size and number increased. This finding is also in accordance with some previous reports2,4,6,8,9,11; however, Candau et al.4 and Zanetti et al.12 failed to demonstrate any significant difference in outcome depending on the size of the residual stones. The spontaneous clearance rate was highest in the renal pelvis, followed by the inferior calix and then other sites. Fialkov et al.11 found that only in middle calices was the likelihood of the need for a 22
secondary procedure significantly increased. Candau et al.4 observed the poorest clearance rate in the superior calix and the highest in the pelvis, followed by the middle and inferior calices. Others have reported better clearance of residual fragments in the upper calix than in the inferior calix (46% to 64% versus 64% to 71%).3,13 However, the number of patients with residual fragments in the upper and middle calices were small in our report, and it is difficult to draw a statistically valid conclusion. Zanetti et al.12 and Moon and Kim14 found that the location of residual fragments did not significantly affect the clearance rate. We noted that clearance continued up to 12 months after ESWL, as in other series.5,14 –16 However, some studies have shown that the duration of follow-up does not significantly influence the stone-free rate after ESWL for caliceal calculi.17,18 In our study, when the metabolic defect was kept under control with specific medical therapy, the patients had outcomes similar to those without any underlying metabolic abnormality. Pak and Resnick19 also had reported that selective medical therapy is effective in avoiding regrowth of residual fragments. Endoscopic interventions like percutaneous nephrolithotomy and ureteroscopy achieved high clearance rates in patients with complications compared with repeated ESWL. This is in contradiction to some reports,14,20 in which repeated UROLOGY 59 (1), 2002
ESWL was suggested as an “appropriate adjunctive measure.” Patients may improve symptomatically by repeated ESWL and their stone size may decrease to less than 4 mm; however, complete clearance may not occur, as happened in the present study (81% of patients who underwent repeated ESWL). The above results raise questions concerning the attitude needed in respect to residual fragments. With the aim of improving the clearance of residual fragments, various investigators have proposed early retreatment and with this protocol achieved success in 40% to 83% of patients with CIRFs,20,21 but systematic retreatment of all asymptomatic patients was not justified by others.7,10,12,22 Moon and Kim14 observed that retreatment of small fragments with a piezoelectric lithotriptor 1 month after the first treatment eliminated residual fragments in 92% of patients at 6 months of follow-up. Similar results were reported by Krings et al.20 Vibration massage has also been shown to increase the clearance rate of fragments.23 Cicerello et al.24 demonstrated that administration of citrate resulted in clearance of residual fragments at 12 months, increasing the stone-free rate from 32% to 74% in cases of sterile calcium oxalate stones and from 40% to 86% for infectious stones. Fine et al.25 also showed that medical management decreased the regrowth of residual fragments. Until now, there is no univocal management for residual fragments with recognized efficiency, and it needs to be evaluated by more prospective studies. All the statistics mentioned above on the results and recurrences after ESWL refer to patients in whom only a plain film documented complete stone clearance. This examination can miss up to 35% of residual stones.26 Laminated tomography increases the detection rate by 18%.26 The most sensitive method of detecting residual stones is undoubtedly computed tomography.5,27,28 Fragments down to 1 mm in size are visible, and even radiolucent uric acid or cystine calculi are shown with a density that compares to that of calcium-containing stones. In practical terms, however, precision imaging of a very small fragment is probably an unnecessary, time-consuming, and expensive procedure. Sonography provides comparable precision and detects stones down to a diameter of 2 mm. Gaucher et al.27 noted ultrasonography to be inferior to plain x-ray abdominal films; and tomography did not add significantly to the detection rate. Delvecchio and Preminger5 found that the sensitivity of sonography is between 65% and 95% for the detection of urolithiasis and recommended that it should be used only as a complement to abdominal radiography. Most urologists acknowledge that plain abdominal radiographs and plain tomographs are the reference standard to assess UROLOGY 59 (1), 2002
stone burden.29 The interobserver variability in the identification of stones is significantly less with tomography than with plain abdominal radiography.28 However, most patients, treated with ESWL, undergo only plain abdominal radiographs before and after ESWL.30 Although we did not use tomographs in our study, which may have overestimated the number of patients who were truly stone free, we do not believe this limitation would have had an impact on the rate of detecting clinically significant stones as observed by others.25 In conclusion, patients with residual stone fragments after ESWL require close follow-up and timely adjuvant therapy. Because of the reasons mentioned above, we now use the term CIRFs with great caution. We found that as the number and size of the residual fragments increased, the risk of developing complications increased. The pelvic location was a favorable factor for spontaneous passage, and the maximal clearance was noted in the first 6 months after ESWL. In patients with metabolic defects, if treated adequately, the regrowth rate was comparable to those without any metabolic abnormality. Although the complete clearance rate with repeated ESWL was lower than with operative interventions, most patients improved with this modality. Hence, we believe that CIRFs are a myth, the concept needs to be redefined, and more prospective studies should be conducted addressing, not only various prognostic factors as done in the present study, but also correlating the impact of the pelvicaliceal anatomy in the clearance of residual fragments. REFERENCES 1. Lingeman JE, Newman D, Mertz JH, et al: Extracorporeal shockwave lithotripsy: the Methodist Hospital of Indiana experience. J Urol 135: 1134 –1137, 1986. 2. Streem SB, Yost A, and Mascha E: Clinical implications of clinically insignificant store fragments after extracorporeal shock wave lithotripsy. J Urol 155: 1186 –1190, 1996. 3. Drach GW, Dretler S, Fair W, et al: Reports of the United States cooperative study of extracorporeal shock wave lithotripsy. J Urol 135: 1127–1133, 1986. 4. Candau C, Saussine C, Lang H, et al: Natural history of residual renal stone fragments after ESWL. Eur Urol 37: 18 – 22, 2000. 5. Delvecchio FC, and Preminger GM: Management of residual stones. Urol Clin North Am 27: 347–354, 2000. 6. Zanetti G, Montanari E, Mandressi A, et al: Long-term results of extracorporeal shockwave lithotripsy in renal stone treatment. J Endourol 5: 61– 64, 1991. 7. Newman DM, Scott JW, and Lingeman JE: Two-years follow-up of patients treated with extracorporeal shockwave lithotripsy. J Endourol 2: 163–171, 1988. 8. Tu CC, Lee YH, Hang JK, et al: Long-term stone regrowth and recurrence rates after extracorporeal shockwave lithotripsy. Br J Urol 72: 688 – 691, 1993. 9. Beck EM, and Riehle RA: The fate of residual fragments after extracorporeal lithotripsy monotherapy for infection stones. J Urol 145: 6 –10, 1991. 10. Buchholz NP, Meier-Padel S, and Rutishauser G: Minor 23
residual fragments after extracorporeal shockwave lithotripsy: spontaneous clearance or risk factor for recurrent stone formation? J Endourol 11: 227–232, 1997. 11. Fialkov JM, Hedican SP, and Fallon B: Reassessing the efficacy of the Dornier MFL-5000 lithotriptor. J Urol 164: 640 – 643, 2000. 12. Zanetti G, Seveso M, Montanari E, et al: Renal stone fragments following shock wave lithotripsy. J Urol 158: 352– 355, 1997. 13. Psihramis KE, Jewett MA, Bombardier C, et al, for the Toronto Lithotripsy Associates: The first 1,000 patients. J Urol 147: 1006 –1009, 1992. 14. Moon YT, and Kim SC: Fate of clinically insignificant residual fragments after extracorporeal shock wave lithotripsy with EDAP LT-01 lithotripter. J Endourol 7: 453– 456, 1993. 15. Mays N, Petruckevitch A, and Burney PG: Results of one and two year follow-up in clinical comparison of extracorporeal shockwave lithotripsy and percutaneous nephrolithotomy in the treatment of renal calculi. Scand J Urol 26: 43– 49, 1992. 16. Sampaio FJB, and Aragao AHM: Limitations of extracorporeal shockwave lithotripsy for lower calyceal stone: anatomic insight. J Endourol 8: 241–247, 1994. 17. Rassweiller J, Kohrmann KU, and Alken P: ESWL, including imaging. Curr Opin Urol 2: 291–299, 1992. 18. Chen RN, and Streem SB: Extracorporeal shockwave lithotripsy for lower pole calculi: long-term radiographic and clinical outcome. J Urol 156: 1572–1575, 1996. 19. Pak CYC, and Resnick MI: Medical therapy and new approaches to management of nephrolithiasis. Urol Clin North Am 27: 243–253, 2000. 20. Krings F, Turek CH, Steinkogler I, et al: Extracorporeal shockwave lithotripsy retreatment (stir-up) promotes discharge of persistent calyceal stone fragments after primary extracorporeal shock wave lithotripsy. J Urol 148: 1040 – 1042, 1992. 21. Liedle B, Jocham D, Schuster C, et al: Long-term results
24
in ESWL-treated urinary stone patients. Urol Res 16: 256, 1988. 22. Renner C, and Rassweiler J: Treatment of renal stones by extracorporeal shock wave lithotripsy. Nephron 81: 71– 81, 1999. 23. Kosar A, Ozturk A, Serel TA, et al: Effect of vibration massage therapy after extracorporeal shockwave lithotripsy in patients with lower caliceal stones. J Endourol 13: 705–707, 1999. 24. Cicerello E, Merlo F, Gambaro G, 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: 5–9, 1994. 25. Fine KF, Pak CYC, and Perminger GM: Effects of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy. J Urol 153: 27– 33, 1995. 26. Denstedt JD, Clayman RV, and Picus DD: Comparison of endoscopic and radiological residual fragment rate following percutaneous nephrolithotripsy. J Urol 145: 703–705, 1991. 27. Gaucher O, Cormier L, Deneuville M, et al: Which is the best performing imaging method for demonstrating residual renal calculi? Prog Urol 8: 493–501, 1998. 28. Lehtoranta K, Mankinen P, Taari K, et al: Residual stones after percutaneous nephrolithotomy: sensitivities of different imaging methods in renal stone detection. Ann Chir Gynaecol 84: 43– 49, 1995. 29. 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 147: 559 – 562, 1992. 30. Sacks JS, Fujardo LL, Hillman BJ, et al: prospective comparison of plain abdominal radiography with conventional and digital renal tomography in assessing renal extracorporeal shockwave lithotripsy patients. J Urol 144: 1341– 1346, 1990.
UROLOGY 59 (1), 2002
POST-ESWL, CLINICALLY INSIGNIFICANT RESIDUAL STONES: REALITY OR MYTH? ANURAG KHAITAN, NARMADA P. GUPTA, ASHOK K. HEMAL, P. N. DOGRA, AMLESH SETH, MONISH ARON
AND
ABSTRACT Objectives. To assess the significance of asymptomatic residual stone fragments of less than 4 mm (clinically insignificant residual fragments [CIRFs]) after extracorporeal shock wave lithotripsy (ESWL). Methods. Eighty-one patients were followed up for 6 to 60 months (mean 15) after ESWL to determine the fate of the CIRFs. Results. Of the 81 patients, 6 were lost to follow-up, leaving 75 patients. During follow-up, fragments passed spontaneously in 18 patients, remained stable in 13 patients, and became clinically significant in 44 patients who developed one or more complications. For the latter patients, repeated ESWL was done in 16, percutaneous nephrolithotomy in 3, and ureteroscopic stone removal in 4 patients. The remaining 21 patients were treated conservatively with analgesics. We found that 53% of the CIRFs located in the pelvis passed spontaneously, and most of the CIRFs in caliceal location became clinically significant. Also, as the stone burden and number of stone fragments increased, the risk of CIRFs becoming clinically significant increased. The outcome was the same whether a metabolic abnormality was present or not, provided the patient received appropriate treatment. The clearance rate was highest in the first 6 months. Finally, as the duration of follow-up increased, the rate of complications increased. Conclusions. Patients with residual stones after ESWL require close follow-up and timely adjuvant therapy. As the number and size of residual fragments increased, the risk of complications increased. A pelvic location was a favorable factor for spontaneous passage. Metabolic defects, if treated adequately, did not increase the regrowth rate. Although the complete clearance rate of CIRFs with repeated ESWL was lower than for the operative interventions, most patients improved with this modality. UROLOGY 59: 20–24, 2002. © 2002, Elsevier Science Inc.
T
he emergence of extracorporeal shock wave lithotripsy (ESWL) as the treatment of choice for most patients with upper tract calculi has brought a new concept of clinically insignificant residual fragments (CIRFs).1,2 The clearance of these fragments is not immediate, and as many as 85% of patients have been reported to have residual fragments in the kidney a few days after ESWL.3 Fragments of more than 5 mm are generally considered a failure of the ESWL session and require treatment.4 The term CIRFs is controversial, because no consensus has been reached regarding the size for its definition or interval after From the Department of Urology, All India Institute of Medical Sciences, New Delhi, India Reprint requests: Narmada P. Gupta, M.D., Department of Urology, All India Institute of Medical Sciences, New Delhi 110029, India Submitted: June 20, 2001, accepted (with revisions): September 7, 2001
20
© 2002, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
ESWL to evaluate its presence. Also, the choice of imaging modality and the treatment required are controversial. These fragments have the potential to cause ureteral obstruction and are important risk factors for stone growth and recurrence. We carried out a prospective study to analyze the fate of such fragments and the intervention required for such a situation. MATERIAL AND METHODS In the past 5 years, 1250 patients with renal stones were treated with ESWL at our center. Of these, complete clearance was achieved in 830 cases, another modality of treatment was required in 130 failed cases, and 209 patients were lost to follow-up. We prospectively followed up the remaining 81 patients who had CIRFs 3 months after the last session of ESWL. Six patients were excluded because of inadequate follow-up data, and the data of the remaining 75 were analyzed. CIRFs were defined as post-ESWL, nonobstructive, noninfectious, asymptomatic (absence of pain, hematuria, and pyuria), residual fragments 4 mm or less in size.5 All patients were 0090-4295/02/$22.00 PII S0090-4295(01)01494-7
TABLE I. Patient characteristics Total patients (n) Lost to follow-up (n) Males/females (n) Right/left (n) Average age (yr) Spontaneous clearance (n) Stable (n) Complications (becoming clinically significant) (n)
81 6 57/18 32/43 36 (range 9–60) 18 13 44
TABLE II. Complications in patients with CIRFs on follow-up Complication
n
Regrowth Pain Recurrent urinary tract infections Increased number of stones Ureteric obstruction Hematuria Hypertension Lower pole nonfunctioning kidney
41 35 5 4 4 2 1 2
KEY: CIRFs ⫽ clinically insignificant residual fragments.
treated using Siemen’s Lithostar Plus. The average size of the CIRFs was assessed in two dimensions for their largest diameter. The stone burden was the sum product of these two diameters for all fragments. Patients were divided into three groups, depending on the stone burden: 10 mm2 or less, 11 to 20 mm2, and greater than 20 mm2. Stone analysis was done by the x-ray diffraction method. The follow-up period ranged from 6 to 60 months (mean 15). The follow-up was done at 3-month intervals with clinical examinations, urinalysis and culture, renal function tests, and abdominal radiography. The location of fragments in the renal pelvis, inferior, middle, or superior calix, and multiple calices was recorded as determined by intravenous urography or ultrasonography. A metabolic evaluation was done on all patients and included urine pH, stone analysis, serum calcium, phosphorus, and uric acid, and 24-hour urinary calcium, phosphorus, uric acid, creatinine, and electrolytes. For patients diagnosed with hyperuricemia, increasing the fluid intake to maintain urine output of more than 2 L/day, a low purine diet, alkalinization, and allopurinol were advised. For those with hypercalcemia, fluid therapy, restricted dairy products and salt intake, alkalinization, and thiazides were used. They were reviewed for adequate control on follow-up visits. Those developing any complication during follow-up received appropriate treatment with repeated ESWL, percutaneous nephrolithotomy, ureteroscopy, or, conservatively, with analgesics.
RESULTS The patient characteristics are shown in Table I. The most common site for CIRFs was the inferior calix followed by the renal pelvis. The other sites were relatively uncommon. Most of the patients with CIRFs had one stone (n ⫽ 39) followed by two, three, and more than three fragments in 15, 4, and 17 patients, respectively. The stone burden was less than 10 mm2, 10 to 20 mm2, and larger than 20 mm2 in 49, 19, and 12 patients, respectively. Stone analysis revealed that 70 patients had calcium oxalate, 4 had uric acid, and 1 had calcium phosphate stones. This stone composition was not significantly different from that in those with complete clearance. During follow-up, fragments passed spontaneously in 18 patients, remained stable in 13, and became clinically significant in 44 patients, who developed one or more complications (Table II). For those who developed complications, repeated ESWL was required in 16 patients, percutaneous nephrolithotomy in 3, and ureteroscopic stone removal in 4. UROLOGY 59 (1), 2002
TABLE III. Interventions conducted for complications and their outcome Outcome (n) Procedure ESWL PCNL URS Partial nephrectomy
Patients (n)
Cleared
Residual (<4 mm)
16 3 4 1
3 3 4 1
13 0 0 0
KEY: ESWL ⫽ extracorporeal shock wave lithotripsy; PCNL ⫽ percutaneous nephrolithotomy; URS ⫽ ureteroscopy.
The remaining 21 patients were treated conservatively with analgesics (Table III). We found that 53% of the CIRFs located in the renal pelvis passed spontaneously, and most CIRFs in a caliceal location became clinically significant (Table IV). Also, as the stone burden increased, the risk of the CIRFs becoming clinically significant increased; similar findings were observed with an increasing number of stone fragments (Table IV). Eighteen patients had a metabolic abnormality. Of these, 14 had hyperuricemia and 4 had hypercalciuria; all received medical therapy. The outcome was the same whether a metabolic abnormality was present or not, provided the patient received appropriate treatment. In patients who required repeated ESWL, 13 of 16 again developed residual fragments of 4 mm or less, and 1 of the 13 later required ureteroscopic stone removal. Thus, stone clearance was achieved in only 3 patients. This was in contrast to those treated with operative intervention, who all achieved complete clearance (Table III). The clearance rate was highest in the first 6 months but did continue for 12 months in some cases. As the duration of follow-up increased, the rate of complications increased. COMMENT Residual fragments represent a common and still controversial problem of ESWL. Although effica21
TABLE IV. Correlation of various prognostic factors with outcome Total Patients (n) Prognostic factor Male Female Right Left Stone burden (mm2) ⬍10 11–20 ⬎20 Stone number 1 2 3 ⬎3 Stone site Pelvic Inferior calix Middle calix Superior calix Multiple calices Metabolic defect Present Absent
Cleared (%) (24.5) (22) (22) (25.6)
Stable (%)
Clinically Significant (%)
8 5 7 6
35 9 18 26
57 18 32 43
14 4 7 11
49 19 12
16 (32.7) 2 (10.5) 2 (16.7)
9 (18.3) 3 (15.8) 1 (8.3)
24 (49) 14 (73.7) 9 (75)
S
39 15 4 17
13 3 0 2
7 3 1 2
(18) (20) (25) (11.8)
19 9 3 13
(48.7) (60) (75) (76.4)
S
6 26 6 2 4
(40) (59) (100) (67) (57.5)
S
(33.3) (20) (0) (11.8)
(14) (28) (22) (14)
15 44 6 3 7
8 (33.3) 9 (20.5) 0 1 (33) 0
1 (6.7) 9 (20.5) 0 0 3 (42.5)
18 57
6 (33.3) 12 (21.1)
2 (11.1) 11 (19.3)
(61.5) (50) (56) (60.4)
Statistical Significance
10 (55.6) 34 (59.6)
NS NS
NS
KEY: NS ⫽ not significant; S ⫽ significant.
cious fragmentation of stones with ESWL into fragments less than 5 mm has been described in 85%3 to 96%1 of cases, residual fragments are still present in 24% to 36% of cases 3 months after ESWL treatment.1,3,5,6 Asymptomatic fragments less than 5 mm and not associated with infection were initially defined as CIRFs, but many investigators have reported regrowth of these fragments in 21% to 70% of cases.2,5–9 In our study, regrowth was seen in 59% of cases, in contrast to the 2% growth rate of residual fragments at a mean follow-up of 2.5 years in the series of Buchholz et al.10 In 24% of patients, stone fragments passed spontaneously. This was comparable with other reports,2,4 but was lower than the 87% clearance rate in a few series.10 The difference may be because in the latter report, patients were included at 1 month after ESWL, not 3 months as in our study. The possibility of CIRFs becoming clinically significant increased as their size and number increased. This finding is also in accordance with some previous reports2,4,6,8,9,11; however, Candau et al.4 and Zanetti et al.12 failed to demonstrate any significant difference in outcome depending on the size of the residual stones. The spontaneous clearance rate was highest in the renal pelvis, followed by the inferior calix and then other sites. Fialkov et al.11 found that only in middle calices was the likelihood of the need for a 22
secondary procedure significantly increased. Candau et al.4 observed the poorest clearance rate in the superior calix and the highest in the pelvis, followed by the middle and inferior calices. Others have reported better clearance of residual fragments in the upper calix than in the inferior calix (46% to 64% versus 64% to 71%).3,13 However, the number of patients with residual fragments in the upper and middle calices were small in our report, and it is difficult to draw a statistically valid conclusion. Zanetti et al.12 and Moon and Kim14 found that the location of residual fragments did not significantly affect the clearance rate. We noted that clearance continued up to 12 months after ESWL, as in other series.5,14 –16 However, some studies have shown that the duration of follow-up does not significantly influence the stone-free rate after ESWL for caliceal calculi.17,18 In our study, when the metabolic defect was kept under control with specific medical therapy, the patients had outcomes similar to those without any underlying metabolic abnormality. Pak and Resnick19 also had reported that selective medical therapy is effective in avoiding regrowth of residual fragments. Endoscopic interventions like percutaneous nephrolithotomy and ureteroscopy achieved high clearance rates in patients with complications compared with repeated ESWL. This is in contradiction to some reports,14,20 in which repeated UROLOGY 59 (1), 2002
ESWL was suggested as an “appropriate adjunctive measure.” Patients may improve symptomatically by repeated ESWL and their stone size may decrease to less than 4 mm; however, complete clearance may not occur, as happened in the present study (81% of patients who underwent repeated ESWL). The above results raise questions concerning the attitude needed in respect to residual fragments. With the aim of improving the clearance of residual fragments, various investigators have proposed early retreatment and with this protocol achieved success in 40% to 83% of patients with CIRFs,20,21 but systematic retreatment of all asymptomatic patients was not justified by others.7,10,12,22 Moon and Kim14 observed that retreatment of small fragments with a piezoelectric lithotriptor 1 month after the first treatment eliminated residual fragments in 92% of patients at 6 months of follow-up. Similar results were reported by Krings et al.20 Vibration massage has also been shown to increase the clearance rate of fragments.23 Cicerello et al.24 demonstrated that administration of citrate resulted in clearance of residual fragments at 12 months, increasing the stone-free rate from 32% to 74% in cases of sterile calcium oxalate stones and from 40% to 86% for infectious stones. Fine et al.25 also showed that medical management decreased the regrowth of residual fragments. Until now, there is no univocal management for residual fragments with recognized efficiency, and it needs to be evaluated by more prospective studies. All the statistics mentioned above on the results and recurrences after ESWL refer to patients in whom only a plain film documented complete stone clearance. This examination can miss up to 35% of residual stones.26 Laminated tomography increases the detection rate by 18%.26 The most sensitive method of detecting residual stones is undoubtedly computed tomography.5,27,28 Fragments down to 1 mm in size are visible, and even radiolucent uric acid or cystine calculi are shown with a density that compares to that of calcium-containing stones. In practical terms, however, precision imaging of a very small fragment is probably an unnecessary, time-consuming, and expensive procedure. Sonography provides comparable precision and detects stones down to a diameter of 2 mm. Gaucher et al.27 noted ultrasonography to be inferior to plain x-ray abdominal films; and tomography did not add significantly to the detection rate. Delvecchio and Preminger5 found that the sensitivity of sonography is between 65% and 95% for the detection of urolithiasis and recommended that it should be used only as a complement to abdominal radiography. Most urologists acknowledge that plain abdominal radiographs and plain tomographs are the reference standard to assess UROLOGY 59 (1), 2002
stone burden.29 The interobserver variability in the identification of stones is significantly less with tomography than with plain abdominal radiography.28 However, most patients, treated with ESWL, undergo only plain abdominal radiographs before and after ESWL.30 Although we did not use tomographs in our study, which may have overestimated the number of patients who were truly stone free, we do not believe this limitation would have had an impact on the rate of detecting clinically significant stones as observed by others.25 In conclusion, patients with residual stone fragments after ESWL require close follow-up and timely adjuvant therapy. Because of the reasons mentioned above, we now use the term CIRFs with great caution. We found that as the number and size of the residual fragments increased, the risk of developing complications increased. The pelvic location was a favorable factor for spontaneous passage, and the maximal clearance was noted in the first 6 months after ESWL. In patients with metabolic defects, if treated adequately, the regrowth rate was comparable to those without any metabolic abnormality. Although the complete clearance rate with repeated ESWL was lower than with operative interventions, most patients improved with this modality. Hence, we believe that CIRFs are a myth, the concept needs to be redefined, and more prospective studies should be conducted addressing, not only various prognostic factors as done in the present study, but also correlating the impact of the pelvicaliceal anatomy in the clearance of residual fragments. REFERENCES 1. Lingeman JE, Newman D, Mertz JH, et al: Extracorporeal shockwave lithotripsy: the Methodist Hospital of Indiana experience. J Urol 135: 1134 –1137, 1986. 2. Streem SB, Yost A, and Mascha E: Clinical implications of clinically insignificant store fragments after extracorporeal shock wave lithotripsy. J Urol 155: 1186 –1190, 1996. 3. Drach GW, Dretler S, Fair W, et al: Reports of the United States cooperative study of extracorporeal shock wave lithotripsy. J Urol 135: 1127–1133, 1986. 4. Candau C, Saussine C, Lang H, et al: Natural history of residual renal stone fragments after ESWL. Eur Urol 37: 18 – 22, 2000. 5. Delvecchio FC, and Preminger GM: Management of residual stones. Urol Clin North Am 27: 347–354, 2000. 6. Zanetti G, Montanari E, Mandressi A, et al: Long-term results of extracorporeal shockwave lithotripsy in renal stone treatment. J Endourol 5: 61– 64, 1991. 7. Newman DM, Scott JW, and Lingeman JE: Two-years follow-up of patients treated with extracorporeal shockwave lithotripsy. J Endourol 2: 163–171, 1988. 8. Tu CC, Lee YH, Hang JK, et al: Long-term stone regrowth and recurrence rates after extracorporeal shockwave lithotripsy. Br J Urol 72: 688 – 691, 1993. 9. Beck EM, and Riehle RA: The fate of residual fragments after extracorporeal lithotripsy monotherapy for infection stones. J Urol 145: 6 –10, 1991. 10. Buchholz NP, Meier-Padel S, and Rutishauser G: Minor 23
residual fragments after extracorporeal shockwave lithotripsy: spontaneous clearance or risk factor for recurrent stone formation? J Endourol 11: 227–232, 1997. 11. Fialkov JM, Hedican SP, and Fallon B: Reassessing the efficacy of the Dornier MFL-5000 lithotriptor. J Urol 164: 640 – 643, 2000. 12. Zanetti G, Seveso M, Montanari E, et al: Renal stone fragments following shock wave lithotripsy. J Urol 158: 352– 355, 1997. 13. Psihramis KE, Jewett MA, Bombardier C, et al, for the Toronto Lithotripsy Associates: The first 1,000 patients. J Urol 147: 1006 –1009, 1992. 14. Moon YT, and Kim SC: Fate of clinically insignificant residual fragments after extracorporeal shock wave lithotripsy with EDAP LT-01 lithotripter. J Endourol 7: 453– 456, 1993. 15. Mays N, Petruckevitch A, and Burney PG: Results of one and two year follow-up in clinical comparison of extracorporeal shockwave lithotripsy and percutaneous nephrolithotomy in the treatment of renal calculi. Scand J Urol 26: 43– 49, 1992. 16. Sampaio FJB, and Aragao AHM: Limitations of extracorporeal shockwave lithotripsy for lower calyceal stone: anatomic insight. J Endourol 8: 241–247, 1994. 17. Rassweiller J, Kohrmann KU, and Alken P: ESWL, including imaging. Curr Opin Urol 2: 291–299, 1992. 18. Chen RN, and Streem SB: Extracorporeal shockwave lithotripsy for lower pole calculi: long-term radiographic and clinical outcome. J Urol 156: 1572–1575, 1996. 19. Pak CYC, and Resnick MI: Medical therapy and new approaches to management of nephrolithiasis. Urol Clin North Am 27: 243–253, 2000. 20. Krings F, Turek CH, Steinkogler I, et al: Extracorporeal shockwave lithotripsy retreatment (stir-up) promotes discharge of persistent calyceal stone fragments after primary extracorporeal shock wave lithotripsy. J Urol 148: 1040 – 1042, 1992. 21. Liedle B, Jocham D, Schuster C, et al: Long-term results
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