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Observation Versus Active Treatment

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Clinical Management of Urolithiasis

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Abstract

Observation vs. active treatment for upper urinary tract stones is discussed in this chapter. Stone-depending factors, anatomical conditions, and patient-depending factors all contribute to the decision to follow an observational approach aiming at an uneventful spontaneous stone expulsion vs. active treatment. Indications and contraindications for each approach are presented. Influential factors for spontaneous stone expulsion and for medical expulsive therapy (MET) are outlined. The pathophysiology and indications for MET are included regarding stone size, location, class effects, combination with corticosteroids, and its adjuvant application together with shock wave lithotripsy (SWL) and ureterorenoscopy (URS). Finally, cost-effectiveness and the dissemination of MET outside urology is discussed.

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References

  • Agarwal MM, Naja V, Singh SK, Mavuduru R, Mete UK, Kumar S, Mandal AK (2009) Is there an adjunctive role of tamsulosin to extracorporeal shockwave lithotripsy for upper ureteric stones: results of an open label randomized nonplacebo controlled study. Urology 74(5):989–992

    Article  PubMed  Google Scholar 

  • Ahmad M, Chaughtai MN, Khan FA (1991) Role of prostaglandin synthesis inhibitors in the passage of ureteric calculus. J Pak Med Assoc 41(11):268–270

    PubMed  CAS  Google Scholar 

  • Ahmed AF, Al-Sayed AY (2010) Tamsulosin versus alfuzosin in the treatment of patients with distal ureteral stones: prospective, randomized, comparative study. Korean J Urol 51(3):193–197

    Article  PubMed  Google Scholar 

  • Al-Ansari A, Al-Naimi A, Alobaidy A, Assadiq K, Azmi MD, Shokeir AA (2010) Efficacy of tamsulosin in the management of lower ureteral stones: a randomized double-blind placebo-controlled study of 100 patients. Urology 75(1):4–7

    Article  PubMed  Google Scholar 

  • Autorino R, De Sio M, Damiano R, Di Lorenzo G, Perdonà S, Russo A, Quarto G, Cosentino L, D’Armiento M (2005) The use of tamsulosin in the medical treatment of ureteral calculi: where do we stand? Urol Res 33(6):460–464

    Article  PubMed  Google Scholar 

  • Aydogdu O, Burgu B, Gucuk A, Suer E, Soygur T (2009) Effectiveness of doxazosin in treatment of distal ureteral stones in children. J Urol 182(6):2880–2884

    Article  PubMed  CAS  Google Scholar 

  • Bensalah K, Pearle M, Lotan Y (2008) Cost-effectiveness of medical expulsive therapy using alpha-blockers for the treatment of distal ureteral stones. Eur Urol 53(2):411–418

    Article  PubMed  Google Scholar 

  • Bhagat SK, Chacko NK, Kekre NS, Gopalakrishnan G, Antonisamy B, Devasia A (2007) Is there a role for tamsulosin in shock wave lithotripsy for renal and ureteral calculi? J Urol 177(6):2185–2188

    Article  PubMed  CAS  Google Scholar 

  • Borghi L, Meschi T, Amato F, Novarini A, Giannini A, Quarantelli C, Mineo F (1994) Nifedipine and methylprednisolone in facilitating ureteral stone passage: a randomized, double-blind, placebo-controlled study. J Urol 152(4):1095–1098

    PubMed  CAS  Google Scholar 

  • Brede C, Hollingsworth JM, Faerber GJ, Taylor JS, Wolf JS (2010) Medical expulsive therapy for ureteral calculi in the real world: targeted education increases use and improves patient outcome. J Urol 183(2):585–589

    Article  PubMed  Google Scholar 

  • Chau LH, Tai DC, Fung BT, Li JC, Fan CW, Li MK (2011) Medical expulsive therapy using alfuzosin for patient presenting with ureteral stone less than 10 mm: a prospective randomized controlled trial. Int J Urol 18(7):510–514

    Article  PubMed  CAS  Google Scholar 

  • Collins JW, Keeley FX (2002) Is there a role for prophylactic shock wave lithotripsy for asymptomatic calyceal stones? Curr Opin Urol 12(4):281–286

    Article  PubMed  Google Scholar 

  • Cooper JT, Stack GM, Cooper TP (2000) Intensive medical management of ureteral calculi. Urology 56(4):575–578

    Article  PubMed  CAS  Google Scholar 

  • Davenport K, Timoney AG, Keeley FX (2006) A comparative in vitro study to determine the beneficial effect of calcium-channel and alpha(1)-adrenoceptor antagonism on human ureteric activity. BJU Int 98(3):651–655

    Article  PubMed  CAS  Google Scholar 

  • Davenport K, Timoney AG, Keeley FX (2007) Effect of smooth muscle relaxant drugs on proximal human ureteric activity in vivo: a pilot study. Urol Res 35(4):207–213

    Article  PubMed  CAS  Google Scholar 

  • Dellabella M, Milanese G, Muzzonigro G (2003) Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones. J Urol 170(6 Pt 1):2202–2205

    Article  PubMed  CAS  Google Scholar 

  • Dellabella M, Milanese G, Muzzonigro G (2005a) Medical-expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life. Urology 66(4):712–715

    Article  PubMed  Google Scholar 

  • Dellabella M, Milanese G, Muzzonigro G (2005b) Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi. J Urol 174(1):167–172

    Article  PubMed  CAS  Google Scholar 

  • Glowacki LS, Beecroft ML, Cook RJ, Pahl D, Churchill DN (1992) The natural history of asymptomatic urolithiasis. J Urol 147(2):319–321

    PubMed  CAS  Google Scholar 

  • Gravas S, Tzortzis V, Karatzas A, Oeconomou A, Melekos MD (2007) The use of tamsulozin as adjunctive treatment after SWL in patients with distal ureteral stone: do we really need it? Results from a randomised study. Urol Res 35(5):231–235

    Article  PubMed  CAS  Google Scholar 

  • Gravina GL, Costa AM, Ronchi P, Galatioto GP, Angelucci A, Castellani D, Narcisi F, Vicentini C (2005) Tamsulosin treatment increases clinical success rate of single extracorporeal shock wave lithotripsy of renal stones. Urology 66(1):24–28

    Article  PubMed  Google Scholar 

  • Han M, Park Y, Shim B (2006) Effect of tamsulosin on the ecpectant treatment of lower ureteral stones. Korean J Urol 47:708–711

    Article  Google Scholar 

  • Hermanns T, Sauermann P, Rufibach K, Frauenfelder T, Sulser T, Strebel RT (2009) Is there a role for tamsulosin in the treatment of distal ureteral stones of 7 mm or less? Results of a randomised, double-blind, placebo-controlled trial. Eur Urol 56(3):407–412

    Article  PubMed  Google Scholar 

  • Hertle L, Nawrath H (1984a) Calcium channel blockade in smooth muscle of the human upper urinary tract. I. Effects on depolarization-induced activation. J Urol 132(6):1265–1269

    PubMed  CAS  Google Scholar 

  • Hertle L, Nawrath H (1984b) Calcium channel blockade in smooth muscle of the human upper urinary tract. II. Effects on norepinephrine-induced activation. J Urol 132(6):1270–1274

    PubMed  CAS  Google Scholar 

  • Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, Minneman KP, Ruffolo RR (1995) International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update. Pharmacol Rev 47(2):267–270

    PubMed  CAS  Google Scholar 

  • Holdgate A, Oh CM (2005) Is there a role for antimuscarinics in renal colic? A randomized controlled trial. J Urol 174(2):572–575, discussion 575

    Article  PubMed  Google Scholar 

  • Hollingsworth JM, Rogers MA, Kaufman SR, Bradford TJ, Saint S, Wei JT, Hollenbeck BK (2006) Medical therapy to facilitate urinary stone passage: a meta-analysis. Lancet 368(9542):1171–1179

    Article  PubMed  Google Scholar 

  • Hollingsworth JM, Wolf JS, Faerber GJ, Roberts WW, Dunn RL, Hollenbeck BK (2010) Understanding the barriers to the dissemination of medical expulsive therapy. J Urol 184(6):2368–2372

    Article  PubMed  Google Scholar 

  • Holmlund D, Hassler O (1965) A method of studying the ureteral reaction to artificial concrements. Acta Chir Scand 130(4):335–343

    PubMed  CAS  Google Scholar 

  • Hübner W, Porpaczy P (1990) Treatment of caliceal calculi. Br J Urol 66(1):9–11

    Article  PubMed  Google Scholar 

  • Hübner WA, Irby P, Stoller ML (1993) Natural history and current concepts for the treatment of small ureteral calculi. Eur Urol 24(2):172–176

    PubMed  Google Scholar 

  • Irving SO, Calleja R, Lee F, Bullock KN, Wraight P, Doble A (2000) Is the conservative management of ureteric calculi of >4 mm safe? BJU Int 85(6):637–640

    Article  PubMed  CAS  Google Scholar 

  • Itoh Y, Kojima Y, Yasui T, Tozawa K, Sasaki S, Kohri K (2007) Examination of alpha 1 adrenoceptor subtypes in the human ureter. Int J Urol 14(8):749–753

    Article  PubMed  CAS  Google Scholar 

  • Itoh Y, Okada A, Yasui T, Hamamoto S, Hirose M, Kojima Y, Tozawa K, Sasaki S, Kohri K (2011) Efficacy of selective α1A adrenoceptor antagonist silodosin in the medical expulsive therapy for ureteral stones. Int J Urol 18(9):672–674

    PubMed  CAS  Google Scholar 

  • John TT, Razdan S (2010) Adjunctive tamsulosin improves stone free rate after ureteroscopic lithotripsy of large renal and ureteric calculi: a prospective randomized study. Urology 75(5):1040–1042

    Article  PubMed  Google Scholar 

  • Kaneko T, Matsushima H, Morimoto H, Tsuzaka Y, Homma Y (2010) Efficacy of low dose tamsulosin in medical expulsive therapy for ureteral stones in japanese male patients: a randomized controlled study. Int J Urol 17(5):462–465. Epub 2010 Feb 25

    Google Scholar 

  • Keeley FX, Tilling K, Elves A, Menezes P, Wills M, Rao N, Feneley R (2001) Preliminary results of a randomized controlled trial of prophylactic shock wave lithotripsy for small asymptomatic renal calyceal stones. BJU Int 87(1):1–8

    Article  PubMed  Google Scholar 

  • Keshvary M, Taghavi R, Arab D (2006) The effect of tamsulosine and nifedipine in facilitating juxtavesical stones passage. Med J Mashhad Univ Med Sci 48:425–430

    Google Scholar 

  • Kim T, Oh S, Moon Y (2008) The effect of tamsulosin on expulsion of ureteral stones after extracorporeal shock wave lithotripsy. Korean J Urol 49:1100–1104

    Article  Google Scholar 

  • Küpeli B, Irkilata L, Gürocak S, Tunç L, Kiraç M, Karaoğlan U, Bozkirli I (2004) Does tamsulosin enhance lower ureteral stone clearance with or without shock wave lithotripsy? Urology 64(6):1111–1115

    Article  PubMed  Google Scholar 

  • Laerum E, Ommundsen OE, Grønseth JE, Christiansen A, Fagertun HE (1995) Oral diclofenac in the prophylactic treatment of recurrent renal colic. A double-blind comparison with placebo. Eur Urol 28(2):108–111

    PubMed  CAS  Google Scholar 

  • Liatsikos EN, Katsakiori PF, Assimakopoulos K, Voudoukis T, Kallidonis P, Constantinides C, Athanasopoulos A, Stolzenburg JU, Perimenis P (2007) Doxazosin for the management of distal-ureteral stones. J Endourol 21(5):538–541

    Article  PubMed  CAS  Google Scholar 

  • Mastrangelo D, Wisard M, Rohner S, Leisinger H, Iselin CE (2000) Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. Urol Res 28(6):376–382

    Article  PubMed  CAS  Google Scholar 

  • Micali S, Grande M, Sighinolfi MC, De Stefani S, Bianchi G (2007) Efficacy of expulsive therapy using nifedipine or tamsulosin, both associated with ketoprofene, after shock wave lithotripsy of ureteral stones. Urol Res 35(3):133–137

    Article  PubMed  CAS  Google Scholar 

  • Mikkelsen AL, Meyhoff HH, Lindahl F, Christensen J (1988) The effect of hydroxyprogesterone on ureteral stones. Int Urol Nephrol 20(3):257–260

    Article  PubMed  CAS  Google Scholar 

  • Miller OF, Kane CJ (1999) Time to stone passage for observed ureteral calculi: a guide for patient education. J Urol 162(3 Pt 1):688–690, discussion 690–1

    Article  PubMed  CAS  Google Scholar 

  • Mohseni MG, Hosseini SR, Alizadeh F (2006) Efficacy of terazosin as a facilitator agent for expulsion of the lower ureteral stones. Saudi Med J 27(6):838–840

    PubMed  Google Scholar 

  • Ohgaki K, Horiuchi K, Hikima N, Kondo Y (2010) Facilitation of expulsion of ureteral stones by addition of α1-blockers to conservative therapy. Scand J Urol Nephrol 44(6):420–424

    Article  PubMed  CAS  Google Scholar 

  • Pedro RN, Hinck B, Hendlin K, Feia K, Canales BK, Monga M (2008) Alfuzosin stone expulsion therapy for distal ureteral calculi: a double-blind, placebo controlled study. J Urol 179(6):2244–2247, discussion 2247

    Article  PubMed  Google Scholar 

  • Phillips E, Hinck B, Pedro R, Makhlouf A, Kriedberg C, Hendlin K, Monga M (2009) Celecoxib in the ­management of acute renal colic: a randomized controlled clinical trial. Urology 74(5):994–999

    Article  PubMed  Google Scholar 

  • Porpiglia F, Destefanis P, Fiori C, Fontana D (2000) Effectiveness of nifedipine and deflazacort in the management of distal ureter stones. Urology 56(4):579–582

    Article  PubMed  CAS  Google Scholar 

  • Porpiglia F, Destefanis P, Fiori C, Scarpa RM, Fontana D (2002) Role of adjunctive medical therapy with nifedipine and deflazacort after extracorporeal shock wave lithotripsy of ureteral stones. Urology 59(6):835–838

    Article  PubMed  CAS  Google Scholar 

  • Porpiglia F, Ghignone G, Fiori C, Fontana D, Scarpa RM (2004) Nifedipine versus tamsulosin for the management of lower ureteral stones. J Urol 172(2):568–571

    Article  PubMed  CAS  Google Scholar 

  • Porpiglia F, Vaccino D, Billia M, Renard J, Cracco C, Ghignone G, Scoffone C, Terrone C, Scarpa RM (2006) Corticosteroids and tamsulosin in the medical expulsive therapy for symptomatic distal ureter stones: single drug or association? Eur Urol 50(2):339–344

    Article  PubMed  CAS  Google Scholar 

  • Preminger GM, Tiselius HG, Assimos DG, Alken P, Buck AC, Gallucci M, Knoll T, Lingeman JE, Nakada SY, Pearle MS, Sarica K, Türk C, Wolf JS, American Urological Association Education and Research Ic, Urology EAo (2007a) 2007 Guideline for the management of ureteral calculi. Eur Urol 52(6):1610–1631

    Article  PubMed  Google Scholar 

  • Preminger GM, Tiselius HG, Assimos DG, Alken P, Buck C, Gallucci M, Knoll T, Lingeman JE, Nakada SY, Pearle MS, Sarica K, Türk C, Wolf JS, Panel EANG (2007b) 2007 Guideline for the management of ureteral calculi. J Urol 178(6):2418–2434

    Article  PubMed  Google Scholar 

  • Quan W, Wu Z, Li HY, Liang ZH, Wang LM (2007) Alpha1-adrenergic blockers treatment increases clinical success rate of single extracorporeal shock wave lithotripsy of renal and ureteral calculi. J Clin Urol (China) 22:210–2

    Google Scholar 

  • Sahin A, Erdemli I, Bakkaloglu M, Ergen A, Basar I, Remzi D (1993) The effect of nifedipine and verapamil on rhythmic contractions of human isolated ureter. Arch Int Physiol Biochim Biophys 101(5):245–247

    Article  PubMed  CAS  Google Scholar 

  • Saita A, Bonaccorsi A, Marchese F, Condorelli SV, Motta M (2004) Our experience with nifedipine and prednisolone as expulsive therapy for ureteral stones. Urol Int 72(Suppl 1):43–45

    Article  PubMed  CAS  Google Scholar 

  • Sayed MA, Abolyosr A, Abdalla MA, El-Azab AS (2008) Efficacy of tamsulosin in medical expulsive therapy for distal ureteral calculi. Scand J Urol Nephrol 42(1):59–62

    Article  PubMed  CAS  Google Scholar 

  • Schlotmann A, Clorius JH, Clorius SN (2009) Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery. Eur J Nucl Med Mol Imaging 36(10):1665–1673

    Article  PubMed  Google Scholar 

  • Schneider T, Fetscher C, Krege S, Michel MC (2004) Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther 309(3):1148–1153

    Article  PubMed  CAS  Google Scholar 

  • Seitz C, Fajkovic H (2011) Medikamentöse Passageer­leichterung von Uretersteinen: eine Metaanalyse. Der Urologe 50(Suppl 1):20 (V5.2)

    Google Scholar 

  • Seitz C, Liatsikos E, Porpiglia F, Tiselius HG, Zwergel U (2009) Medical therapy to facilitate the passage of stones: what is the evidence? Eur Urol 56(3):455–471

    Article  PubMed  Google Scholar 

  • Singh SK, Pawar DS, Griwan MS, Indora JM, Sharma S (2011) Role of tamsulosin in clearance of upper ureteral calculi after extracorporeal shock wave lithotripsy: a randomized controlled trial. Urol J 8(1):14–20

    PubMed  Google Scholar 

  • Sun X, He L, Ge W, Lv J (2009) Efficacy of selective alpha1D-blocker naftopidil as medical expulsive therapy for distal ureteral stones. J Urol 181(4):1716–1720

    Article  PubMed  CAS  Google Scholar 

  • Türk C, Knoll T, Petrik A, Sarica K, Straub M, Seitz C (2011) Guidelines on urolithiasis vol. Presented at 26th EAU congress, Vienna, Austria, 18–22 Mar 2011

    Google Scholar 

  • Uberti MA, Hall RA, Minneman KP (2003) Subtype-specific dimerization of alpha 1-adrenoceptors: effects on receptor expression and pharmacological properties. Mol Pharmacol 64(6):1379–1390

    Article  PubMed  CAS  Google Scholar 

  • Vincendeau S, Bellissant E, Houlgatte A, Doré B, Bruyère F, Renault A, Mouchel C, Bensalah K, Guillé F, Group TS (2010) Tamsulosin hydrochloride vs placebo for management of distal ureteral stones: a multicentric, randomized, double-blind trial. Arch Intern Med 170(22):2021–2027

    Article  PubMed  CAS  Google Scholar 

  • Wang CJ, Huang SW, Chang CH (2008) Efficacy of an alpha1 blocker in expulsive therapy of lower ureteral stones. J Endourol 22(1):41–46

    Article  PubMed  Google Scholar 

  • Wang CJ, Huang SW, Chang CH (2009) Adjunctive medical therapy with an alpha-1A-specific blocker after shock wave lithotripsy of lower ureteral stones. Urol Int 82(2):166–169

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Liu K, Ji Z, Li H (2010) Effect of alpha1-adrenergic antagonists on lower ureteral stones with extracorporeal shock wave lithotripsy. Asian J Surg 33(1):37–41

    Article  PubMed  CAS  Google Scholar 

  • Worster A, Richards C (2005) Fluids and diuretics for acute ureteric colic. Cochrane Database Syst Rev (3): CD004926

    Google Scholar 

  • Yamaguchi K, Minei S, Yamazaki T, Kaya H, Okada K (1999) Characterization of ureteral lesions associated with impacted stones. Int J Urol 6(6):281–285

    Article  PubMed  CAS  Google Scholar 

  • Ye Z, Yang H, Li H, Zhang X, Deng Y, Zeng G, Chen L, Cheng Y, Yang J, Mi Q, Zhang Y, Chen Z, Guo H, He W (2011) A multicentre, prospective, randomized trial: comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy for distal ureteric stones with renal colic. BJU Int 108(2):276–279

    Article  PubMed  CAS  Google Scholar 

  • Yencilek F, Erturhan S, Canguven O, Koyuncu H, Erol B, Sarica K (2010) Does tamsulosin change the management of proximally located ureteral stones? Urol Res 38(3):195–199

    Article  PubMed  Google Scholar 

  • Yilmaz E, Batislam E, Basar MM, Tuglu D, Ferhat M, Basar H (2005) The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones. J Urol 173(6):2010–2012

    Article  PubMed  CAS  Google Scholar 

  • Zehri AA, Ather MH, Abbas F, Biyabani SR (2010) Preliminary study of efficacy of doxazosin as a medical expulsive therapy of distal ureteric stones in a randomized clinical trial. Urology 75(6):1285–1288

    Article  PubMed  Google Scholar 

  • Zheng S, Liu LR, Yuan HC, Wei Q (2010) Tamsulosin as adjunctive treatment after shockwave lithotripsy in patients with upper urinary tract stones: a systematic review and meta-analysis. Scand J Urol Nephrol 44(6):425–432

    Article  PubMed  CAS  Google Scholar 

  • Zheng W, Beiko DT, Segura JW, Preminger GM, Albala DM, Denstedt JD (2002) Urinary calculi in aviation pilots: what is the best therapeutic approach? J Urol 168(4 Pt 1):1341–1343

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, St. John of God Hospital, Academic Teaching Hospital of the Medical University of Vienna, Vienna, Austria

    Christian Seitz FEBU

  2. Department of Urology, General Hospital St. Pölten, St. Pölten, Austria

    Harun Fajkovic

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  1. Christian Seitz FEBU
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Correspondence to Christian Seitz FEBU .

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  1. Klinik für Urologie, Klinikum Sindelfingen-Böblingen, Arthur-Gruber-Str. 70, Sindelfingen, 71065, Baden-Württemberg, Germany

    Thomas Knoll

  2. Center, Department of Urology, UT Southwestern Medical, 5323 Harry Hines, Blvd, Dallas, 75390, Texas, USA

    Margaret S. Pearle

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Seitz, C., Fajkovic, H. (2013). Observation Versus Active Treatment. In: Knoll, T., Pearle, M. (eds) Clinical Management of Urolithiasis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28732-9_4

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