Treatment Strategies of Ureteral Stones



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eau-ebu update series 4 (2006) 184 190 available at www.sciencedirect.com journal homepage: www.europeanurology.com Treatment Strategies of Ureteral Stones Stefanos Papadoukakis a, Jens-Uwe Stolzenburg b, Michael C. Truss a, * a Department of Urology, Klinikum Dortmund, Dortmund, Germany b Department of Urology, University of Leipzig, Leipzig, Germany Article info Keywords: Urolithiasis Ureteral stones Ureteroscopy Lithotripsy Abstract Urinary stone disease is a major health care problem due to its high prevalence and incidence. There are different therapeutic approaches for ureteral stones depending on stone size, location and anatomical variations of the urogenital tract. Watchful waiting with concomitant medication (i.e., analgetics, anti-inflammatory agents, alpha-blockers) is considered an option for smaller stones (<6 mm) that have a high probability for spontaneous passage. Extracorporeal shock wave lithotripsy is a minimally invasive therapeutic approach which has been widely used through the past 20 years. It is a standardized procedure which results in stone free rates between 59% and 100% depending on the size and the location of the stone as well as the type of the lithotriptor. However, more than one session are frequently needed and ureteral stenting is still a matter of debate. Ureteroscopy results in stone free rates of almost 95% in a single session. Stone removal may be achieved with forceps and baskets and with or without intraureteral stone disintegration with various lithotripsy devices. Treatment approaches should be individualized in order to achieve optimum outcomes. # 2006 European Association of Urology and European Board of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Klinikum Dortmund ggmbh, Münsterstr. 240, D-44145 Dortmund. Tel. +49 231 953 18700; Fax: +49 231 953 18790. E-mail address: Michael.truss@klinikumdo.de (M.C. Truss). 1. Introduction, epidemiology and stone composition Urinary stones are the third most common affliction of the urinary tract, exceeded only by urinary tract infections and pathologic conditions of the prostate (BPH and prostate cancer). Stone disease has been a major problem afflicting human population ever since the antiquity. Early reports of the disease can be found in the Aphorisms of Hipparchos and even in Hippocrates. The disease is both very common 1871-2592/$ see front matter # 2006 European Association of Urology and European Board of Urology. Published by Elsevier B.V. All rights reserved. among men and women with estimated prevalence among the population of 2 3% and an estimated lifetime risk of 12% for white males [1] and 5 6% for white females [2]. The life time recurrence rate is approximately 50% [3]. The interval between recurrences is variable, with approximately 10% within one year, 35% within five years, and 50% within 10 years [2]. The increased incidence of urinary stones in the industrialized world is associated with improved standards of living (mainly including the high dietary intake of proteins and minerals) as well doi:10.1016/j.eeus.2006.07.004

eau-ebu update series 4 (2006) 184 190 185 as with race, ethnicity and region of residence [4]. A seasonal variation is also seen, with high urinary calcium oxalate saturation in men during summer and in women during early winter [5]. Stones form twice as often in men as in women. The peak age in men is 30 years; women have a bimodal age distribution, with peaks at 35 and 55 years. The composition of the urinary stones can vary considerably (calcium oxalate, calcium phosphate, uric acid, ammonium urate, sodium urate, magnesium ammonium phosphate, carbonate apatite, cystine, xanthine, sulphonamide and indinavir stones). Many theories have been proposed for the pathogenesis of urolithiasis, including nucleation theory, the crystal inhibitor theory or even the crystal retention theory. Moreover there are a number of diseases associated with stone formation (i.e., hyperparathyroidism, renal tubular acidosis, cystinuria, hyperoxaluria, intestinal malabsorptive conditions) as well as medications (i.e., calcium supplements, vitamin D, triamterene, indinavir). Predisposing factors for stone formation also include anatomical abnormalities (i.e., ureteral strictures, vesico-ureteral reflux, ureteropelvic stenosis, extrinsic ureteral compression and ureterocele among others). Most of the urinary stones pass through the renal calyces to the pelvis and subsequently to the ureter. Primary stone formation in the ureter requires an already existing obstructed urinary flow. Despite an improved understanding of the mechanisms of stone formation it is obvious that ureteral stones are still a problem afflicting an increasing number of patients worldwide. Advances in technology have led to a wide armamentarium for the treatment of the urinary stones. 2. Watchful waiting The initial step of any adequate management of the ureteral stones should be considered the relief of pain. Pain relief may be achieved by the administration of various agents through different routes. Diclofenac sodium, indomethacine, ibuprofen, methamizol, tramadol, pentazocine and hydromorphone with atropine sulphate are among the most frequently used agents. Comparative studies between diclofenac and other agents proved diclofenac to be superior to narcotic analgetics [6] (showing fewer side effects), while on the other hand showed no difference compared to Ketoprofen [7]. Moreover it has been speculated that diclofenac may be able to prevent recurrent episodes of renal colic if given on a regular basis (50 mg t.i.d) [8]. Table 1 Stone size, location and spontaneous passage rate [10,13] Stone size, location Stone passage rate <4 mm 80% <7 mm proximal ureter 25% <7 mm mid ureter 45% <7 mm distal ureter 70% The treatment strategy of watchful waiting with ultrasound follow-up is an appealing and efficacious approach for ureteral stones with a diameter of 7 mm. Ureteral stones of less than 4 mm in diameter have a chance of over 80% to pass spontaneously [9]. On the contrary, most stones with a diameter >8 mm will ultimately necessitate intervention. The spontaneous passage rate depends on the stone burden as well as its location. The overall passage rate is 25% for the proximal ureter stones, 45% for the mid ureter stones and 70% for the distal ureter stones, provided that the mean diameter does not exceed 7 mm (Table 1). Time to spontaneous passage also depends on stone size and location. In one study the mean passage time was between 5 days (for smaller distal stones) and 59 days (for larger proximal stones) [10]. Therefore conservative management within a watchful waiting strategy of 4 to 6 weeks may be reasonable for smaller distal stones if the patient remains asymptomatic. However the presence of an acute infection, the decreased renal function or the persistence of the symptoms despite the analgesic therapy could be among the contraindications for such an approach (Table 2). Recently a number of studies investigated the effect of various drugs on spontaneous stone expulsion of distal ureteral stones. These drugs included analgetics, anti-inflammatory drugs, calcium antagonists such as nifedipine and alphablockers such as tamsulosin. Of the above mentioned agents tamsulosin seems to be especially promising in preliminary studies [11]. Table 2 Contraindications for watchful waiting approach [13] Containdications for watchful waiting approach of ureteral stones Stone diameter >7 mm Inadequate pain relief Concomitant infection Risk of pyonephrosis or sepsis Bilateral obstruction, or unilateral obstruction in single kidneys

186 eau-ebu update series 4 (2006) 184 190 3. Extracorporeal shock wave lithotripsy (ESWL) ESWL has been established as a major therapeutic and minimally invasive option for the treatment of renal stones the last twenty years. Initially, there was uncertainty about the efficacy in the treatment of ureteral stones. There were major concerns due the mobility of ureteral stones, the possible affection of organs outside the urinary tract as well as the applied energy. With increased expertise it has been shown that ESWL is safe and effective in the treatment of ureteral stones. Some early studies reported success and stone free rate after ESWL in up to 90% [12]. It could have been shown that ureteral stones may be treated with ESWL without regional or general anaesthesia and with low complication rate or side effects. The most common side effects of ESWL are local pain, edema of the ureteral mucosa with subsequent mild obstruction and hydronephrosis. The stone free rate is depending on the study, the type of the lithotriptor used, the size of the stone and its location within the ureter. It has been estimated that a mean stone free rate of 77.4% (range 63 100) is achievable for proximal ureter stones, with a retreatment rate of 10%. Data for mid ureteral stones are 80.3%(range 60 98) and 8.2% and for distal ureteral stones 77.9 (range 59 100) and 9.4%, respectively [13] (Table 3). The rather wide range of the above mentioned rates is attributed to the different types of equipment used in each study, the size and the composition of the stone as well as the degree of the impaction and the prior shockwave sessions. In a remarkable study from the United States, 18.825 patients were treated with one to three sessions of ESWL for ureteral stones of variable location and size. All patients were treated within a 6 year follow up period (1988 1993). The mean stone free rate was 83.8% (ranging from 67.9% for stones larger than 20 mm, to 85.8% for stones smaller than 10 mm). The retreatment rate was 10.8% [14]. In the majority of studies only a minor percentage of patients required a previously inserted DJ stent. The vast majority (>80%) was treated with ESWL in Table 3 Stone free rate and retreatment rate after ESWL for ureteral stones Stone location Stone free rate Retreatment rate Proximal ureter 77.4% (63 100%) 10% Mid ureter 80.3% (60 98%) 8.2% Distal ureter 77.9% (59 100%) 9.4% situ without a stent. Interestingly, complication and retreatment rates were not affected by ureteral stents [14]. The introduction of the 2nd generation lithotriptors that use electro hydraulic energy has improved single session stone free rates. The technical development of the latest 3rd generation lithotripters that use electromagnetic energy also led to a reduction of retreatment rates, increased the stone free rate up to 88.5% and reduced treatment time per session to 54(32)min [16]. The fact that ESWL is a minimal invasive procedure that may be applied without local, regional or general anesthesia has made it an attractive alternative in the treatment of ureteral stones. However, stone free rates after a single treatment session still remain still higher with ureteroscopy. 4. Ureteroscopy What started as a therapeutic approach in selected centres has become the standard therapeutic option for the past decade. Ureteroscopy has changed our perception and eventually our treatment strategies of ureteral stones. Ureteroscopy was first described from one of the pioneers in Urology, Hugh Hampton Young back in 1912 [17], but it has not been until the late 70 s that it became a standardized procedure [18]. Alone in the USA the ureteroscopic procedures have increased by 83% in the past 10 years [19]. The ureteroscopic approach has been standardized through the years [20]. The procedure is performed under general or regional anaesthesia in an operative room with fluoroscopic equipment with the patient in the lithotomy position. Prior stenting of the ureter remains a debatable issue. It is not indicated on a routine basis, but only occasionally depending on the size and the shape of the stone, the size of the ureteroscope and the diameter of the ureter. The ultimate goal is the retrievement of the stone, either as one piece (if <10 mm) or in more pieces after its disintegration within the ureter. Indications for an ureteroscopy can be any stone within the ureter, irrespective distal or proximal. If there is a suspicion of any other pathology beside urolithiasis ureteroscopy is the only modality that can actually establish a diagnosis. The clinical outcome of ureteroscopy has been improved considerably over the years. The stone free rates used to be 72% and 90% for proximal and distal ureteral calculi till 1996 [34]. The review of the latest literature shows that the stone free rates with the use of semi rigid or flexible ureteroscopes have

eau-ebu update series 4 (2006) 184 190 187 Table 4 Stone free rate after ureteroscopic extraction Stone location Stone free rate Proximal ureter 74% Distal ureter 90 100% increased to 90 100% for the distal ureteral calculi and to 74% for proximal ureteral stones [35] (Table 4). Moreover an impressive 95% of the patients were stone free after a single procedure [30]. The instruments that are used are either rigid ureteroscopes (9.5 11 F), or semi rigid (6.0 8.5 F) or even flexible ureteroscopes inserted through a 10 13 F sheath. Stone removal is easier with a rigid or a semi rigid instrument, while stone fragmentation with laser may be more feasible with a flexible instrument. The expanded use of flexible ureteroscopes has enabled us to reach stones even within the renal pelvis and calices that have been considered unreachable with rigid ureteroscopes. The miniaturisation of the instruments allows easier access within the ureter without prior dilatation in more than 50% of the patients and easier approach of the proximal ureter [24]. On the other hand, if a stone is localized in the distal ureter, a rigid ureteroscope should be used due to the superior visualisation and therefore better efficacy. Through the working channel of a rigid instrument a variety of tools can be introduced in order to remove the stone in total (if the size is adequate). For smaller distal stones the grasper or the forceps is better since it allows better control in manipulation within the ureter. The ureteroscopic removal of the stone with a basket is a fast approach with minimal morbidity [21]. This approach seems more suitable for small distal ureteral stones and many variable type of baskets (such as nitinol tipples basket) have been developed through the past few years to enable the urologist to remove the stone with minimal or no trauma to the ureteral mucosa and a maximum of intraluminar mobility [22]. Stone disintegration through a rigid ureteroscope can be achieved with in situ lithotripsy. The spectrum of lithotripters includes ultrasonic lithotripsy, electro hydraulic lithotripsy, ballistic lithotripsy, pneumatic lithotripsy, and laser lithotripsy. Good vision throughout the procedure is facilitated with a flow control unit. Laser lithotripsy is a reliable method of stone disintegration irrespective of the stone composition and hardness. It is carried out through all types of ureteroscopes [25]. The Holmium-YAG Laser 365 mm fibre is recommended and used for the treatment of ureteral stones, while the 200 mm fibre is indicated only for intrarenal stones [26]. The Neodymium YAG Laser is also used, with less success, especially in harder stones (i.e., cystine stones), but it remains a cost effective alternative option [27]. The ballistic lithotriptors with probes of 2.4 F are introduced through semi rigid ureterorenoscopes. They are less expensive compared to laser fibres, and provide a fragmentation rate of 90 96% [29]. They are mostly indicated for distal ureteral calculi, because their use in the proximal ureter may lead to stone migration into the renal pelvis and calyces. Using laser lithotriptors the trauma to the urethelial mucosa is usually less compared to the other lithotripters [28]. Comparative studies of the two lithotripsy sources have shown that the Holmium YAG laser seems to give superior stone free rates (97% vs. 87%) [30] (Table 5). For stones <15 mm a ballistic lithotripsy can be regarded as a standard, because of its better efficacy and shorter operative time, while for stones >15 mm a laser lithotripsy should be advised because of its minimal risk of uereteral injury. Post-ureteroscopy stenting has been a matter of debate for the past decade without a final consensus [31]. It is accepted that a DJ stent after a procedure eliminates the risk of hydronephrosis due to mucosal edema. On the other hand ureteral stenting itself is associated with some degreee of morbidity, including stent encrustation, ureteral mucosa erosion, flank pain and irritative voiding symptoms. Recent comparative studies have shown that procedural costs can be reduced by 30% if postoperative stenting is avoided [32,33]. Currently most urologists avoid stenting as long as ureteroscopy was uncomplicated and no dilatation was necessary. Acute intraoperative complications of ureteroscopy have been reported with a rate of 9% and 11% for distal and proximal stones, respectively [34], including ureteral avulsion, intussusception, perforation, false passage, mucosal abrasion, extravasation, thermal injury, equipment malfunction, and bleeding [36]. Postoperative complications Table 5 Stone free rate after various ureteroscopic approaches Ureteroscopic approach Stone free rate Extraction (grasper, basket) 75 95% Ballistic lithotripsy 87% Laser lithotripsy 97%

188 [1] Menon M, Parulkar BC, Drash GW, et al. Urinary lithiasis: etiology, diagnosis, diagnosis and management. In: Walsh PC, editor. Campbell s Urology. 7th edition, Philadelphia: Saunders; 1998. p. 2661 733. [2] Wilkinson H. Clinical investigation and management of patients with renal stones. Ann Clin Biochem 2001;38: 180 7. [3] Bihl G, Meyers A. Recurrent renal stone disease advances in pathogenesis and clinical management. Lancet 2001;358:651 6. [4] Stamatelou KK, Francis ME, Jones CA, Nyberg Jr LM, Curhan GC. Time trends in reported prevalence of kidney stones in the United States: 1976 1994. Kidney Int 2003; 63:1817 23. [5] Parks JH, Barsky R, Coe FL. Gender differences in seasonal variation of urine stone risk factors. J Urol 2003;170: 384 8. [6] Lundstam SO, Leissner KH, Wahlander LA, Kral KG. Prostaglandin-synthetase inhibition of diclofenac sodium in the treatment of renal colic: comparison with use of a narcotic analgesic. Lancet 1982;1096 7. [7] Walden M, Lahtinen J, Elvander E. Analgesic effect and tolerance of ketoprofen and diclofenacc in acute ureteral colic. Scand J Urol Nephrol 1993;27:323 5. [8] Cohen E, Hafner R, Rotenberg Z, Garty M. Comparison of ketorolac and diclofenac in treatment of renal colic. Eur J Clin Pharmacol 1998;54:455 8. [9] Ibrahim Al, Shelty SD, Awad RM, Patel KP. Prognostic factors in the conservative treatment of ureteric stones. Br J Urol 1991;67:358 61. [10] Miller OF, Kane CJ. Time to stone passage for observed ureteral calculi: a guide for patient education. J Urol 1999;162:688 91. [11] Dellabella M, Milanese J, Muzzonigro G. Randomised trial of the efficacy of Tamsulosin, Nifedipin and Phloroglycieau-ebu update series 4 (2006) 184 190 are rather rare (1%) and include urinary retention [15], ureteral strictures, vesicoureteral reflux, and postoperative steinstrasse along with ureteral obstruction [36]. Most of the intraoperative complications are handled with a prolonged postoperative stenting of the ureter [37]. The only exception to this approach is the avulsion of the ureter which requires an immediate operative intervention (i.e., autologous transplantation or ureteral reconstruction with small bowel) [38]. Finally, miniaturization of instruments continues, as shown with the introduction of a 4.5 F ureteroscope [23]. 5. ESWL vs. ureteroscopy There is no real debate or rivalry between those two methods. Both are accepted as the main therapeutic approaches to ureteral stones. ESWL is a minimally invasive method that requires no anesthesia and in most cases no hospitalization of the patient. On the other hand its success rate for distal ureteral calculi is still somewhat less favorable compared to ureteroscopy and in many cases one single session might not be sufficient. Ureteroscopy is an operative procedure with specific indications, extremely high stone free rate and minimal complication rate. Most of the comparative studies between the two methods are not conclusive and sometimes ambiguous. While some studies are in favor of ESWL [15], others concluded that ureteroscopy is the preferable approach [39 41]. 6. Alternative strategies The major treatment strategies for the ureteral stones are the three above mentioned. Nevertheless, chemolysis may also be indicated especially for uric acid stones. One should never forget other conventional techniques, such as open or laparoscopic ureterolithotomy as these options may be indicated in rare circumstances. 7. Conclusion Urinary stone disease is a major health problem that concerns millions of patients worldwide, since it affects 2 3% of the population with a high recurrence rate of almost 50%. The treatment strategies have been altered throughout the years, with the introduction of new technological modalities. The current trends in approaching a ureteral stone depend mostly on the stone size and location in the ureter. A watchful waiting approach, with concomitant medication (pain relief, tamsulosin) is indicated for relative small (<7 mm) stones, localized at the distal ureter. The stone fragmentation using extracorporeal lithotripsy shows good results even in bigger stones, both in the proximal and distal ureter, and remains a less invasive option. The ureteroscopic approach with simultaneous extraction or intraureteral stone fragmentation using various lithotripsy devices is an efficacious single session treatment. There are certain indications, limitations, advantages and disadvantages for each of the above mentioned approaches. The final therapeutic decision should be individualized in every patient (regarding preferences, age, and coexisting comorbidity factors). References

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J Endourol 1992;I-2:46. [24] Puppo P, Riccioti G, Bozzo W, Intoini C. Primary endoscopic treatment of ureterci calculi. A review of 378 cases. Eur Urol 1999;36:48 52. [25] Tawfiek ER, Bagley DH. Management of upper urinary tract calculi with ureteroscopic techniques. Urology 1999;53:25 32. [26] Gould DL. Holmium:YAG Laser and its use in the treatment of urolithiasis: our first 160 cases. J Endourol 1998;12:23 6. [27] Delvechio FC, Auge BK, Brizuela RM, Weizer AZ, Zong P, Preminger GM. In vitro analysis of the stone fragmentation ability of the FREDDY laser. J Endourol 2003;17:177 9. [28] Scarpa RM, De Lisa A, PorruD, Usai E. Holmium YAG laser ureterolithotripsy. Eur Urol 1999;35:233 8. [29] Tan PK, Tan SM, Consigliere D. Ureteroscopic lithoclast lithotripsy: a cost effective option. J Endourol 1998;12: 341 4. [30] Teichman JM, Rao RD, Rogenes VJ, Harris JM. Ureteroscopic management of ureteral calculi: electrohydraulic versus holmium:yag laser lithotripsy. J Urol 1997; 158:1358 61. 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[37] Ferraro RF, Abraham VE, Cohen TD, Preminger GM. A new generation of semirigid fiberoptic ureteroscopes. J Endourol 1999;13:35 40. [38] Martin X, Ndoye A, Konan PG, Feitosa LC, Gelet A, Dawahra M, et al. Hazards of lumbar ureteroscopy: a propos of 4 cases of avulsion of the ureter. Prog Urol 1998;8:358 62. [39] Peschel R, Janetschek G, Bartsch G. Extracorporeal shockwave lithotripsy versus ureteroscopy for distal ureteral calculi: A Prospective randomized study. J Urol 1999;162:1909 12. [40] Turk T, Jenkins A. A comparison of ureteoscopy to in situ extracorporeal schockwave lithotripsy for the treatment of distal ureteral calculi. J Urol 1999;161:45 7. [41] Lotan Y, Gettman M, Roehrborn C, Cadeddu G, Pearle M. Management of ureteral calculi: A cost comparison decision making analysis. J Urol 2002;167:1621 9. CME questions Please visit www.eu-acme.org/europeanurology to answer these CME questions on-line. The CME credits will then be attributed automatically. 1. Which of the following antiviral agents is considered a causative factor for upper urinary tract lithiasis A. Acyclovir B. Gancyclovir C. Indinavir D. Oseltamivir 2. Stone disease recurrence rate is A. 10% for the first 5 years B. 30% for the first year C. 30% life time risk D. 50% for the first 10 years

190 eau-ebu update series 4 (2006) 184 190 3. Which of the following agents, initially introduced for the treatment of BPH/LUTS, has been shown to facilitate ureteral stone passage in preliminary studies. A. Tamsulosin B. Terazosin C. Finasteride D. Serenoa Repens 4. The 3rd generation lithotriptors use A. Electro-hydraulic energy B. Electromagnetic energy C. Ultrasound wave energy D. Laser energy 5. Stone free rates after single session ureteroscopy, reaches A. 95% B. 100% C. 72% D. 80% 6. Which of the following lasers have been widely used in the ureteroscopic disintegration of ureteral stones A. Neodymium YAG laser B. Erbium YAG laser C. Holmium-yttrium laser D. Thulium laser