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Medical Expulsion Therapy for Ureteral Calculi

Medical Expulsion Therapy for Ureteral Calculi. Brian Peters Assistant Professor of Urology Health Sciences Center April 22, 2010. Conflicts of Interest. None. Outline. Ureteral Anatomy Natural History of Ureteral Calculi Different forms of MET Results for CCB and α -blockers.

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Medical Expulsion Therapy for Ureteral Calculi

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  1. Medical Expulsion Therapy for Ureteral Calculi Brian Peters Assistant Professor of Urology Health Sciences Center April 22, 2010

  2. Conflicts of Interest • None

  3. Outline • Ureteral Anatomy • Natural History of Ureteral Calculi • Different forms of MET • Results for CCB and α-blockers

  4. Common locations for stone impaction

  5. Anatomical segments of the Ureter

  6. Natural History • Ueno and colleagues (1977) • 520 patients with ureteral stones • 4 mm 80% • 4 to 6 mm 59% • larger than 6 mm 21% • Morse and Resnick (1991) • Proximal 22% • Middle 46% • Distal 71%

  7. Factors to Consider • Patient • Anatomy • Symptoms • Infection • Level / degree of obstruction • Renal function • Stone • Size • Location • Burden

  8. What therapies have been applied to improve spontaneous passage of Ureteral Calculi?

  9. -NSAIDS included nonselective cyclooxygenase (COX) inhibitors or COX-2 inhibitors decrease ureteral contractions-Don’t affect stone expulsion rates in doubleblind, placebo-controlled trials LaerumE,Ommundsen OE, Grønseth JE, Christiansen A, Fagertun HE.Oral diclofenac in the prophylactic treatment of recurrent renal colic:a double-blind comparison with placebo. Eur Urol 1995;28:108–11. Phillips E, Hinck B, Pedro R. Celecoxib in the management of acute renal colic: a randomized controlled clinical trial. J Endourol 2008;22(Suppl 1):A197.

  10. -Antimuscarinics might relax genitourinary smooth muscle, reducing colic pain and thought to possibly aid in stone passage-Randomised, placebo-controlled trial of Buscopan’s effect on opioid requirement in renal colic showed no favourable effect • Holdgate A, Pollock T. Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. BMJ 2004;328:1401.

  11. Ku¨hn R, U¨ ckert S, Stief CG, et al. Relaxation of human ureteralsmooth muscle in vitro by modulation of cyclic nucleotide-dependentpathways. Urol Res 2000;28:110–5. -Phosphodiesterase (PDE) regulates intracellular cyclic nucleotide turnover, influencing smooth muscle tension -Ureteral smooth muscle relaxing effects of PDE type 4 inhibitor (PDE4-I) and PDE type 5 inhibitor (PDE5-I) in vitro have been reported. -Results similar to those reported for tamsulosin, suggesting the potential for treatment of ureteral colic -Has to be assessed in controlled studies.

  12. -Corticosteroids with anti-inflammatory action reported to facilitate stone expulsion-One randomised trial (published as an abstract) supports a significant effect of methylprednisolone on distal ureteral stone expulsion-Publications in peer-reviewed journals are necessary-No further evidence confirming whether corticosteroids alone are capable of facilitating stone expulsion. • Salehi M, Fouladi Mehr M, Shiery H, et al. Does methylprednisolone acetate increase the success rate of medical therapy for passing distal ureteral stones? Eur Urol Suppl 2005;4(3):25 (abstract 92).

  13. Calcium channel blockers inhibit endogenous prostaglandin synthesis and calcium influx, reducing spontaneous rhythmic contractions of the human ureter • α-blockers inhibit contractions of ureteral musculature, reduce basal tone, and decrease peristaltic frequency and colic pain • Possibly facilitates ureteral stone expulsion and suggesting abeneficial effect for MET

  14. Studies on Flomax and Nifedipine

  15. Randomized Trials with Flomax 0.4mg

  16. Analgesia, hospital visits and days off work for Flomax

  17. Randomized Trials with Nifedipine 30mg

  18. Analgesia, hospital visits and days off work for Nifedipine

  19. MET has greatest efficacy over placebo for stones >5mm, • Below 5mm, study results are mixed, many suggesting no effect • Data on stones >10mm is sparse but MET unlikely to be benefitial

  20. Studies mixed with respect to concomitant steroid use • Some series have reported improved success with addition of corticosteroid • Few people apply this in clinical practice

  21. Flomax vs. Nifedipine • 3 studies • 1 showed no sig. difference • 2 studies have shown superiority of Flomax over Nifedipine in both stone passage rates and time to passage -Dellabella M, Milanese G, Muzzonigro G. Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones. J Urol 2003;170:2202–5. -Porpiglia F, Ghignone G, Fiori C, Fontana D, Scarpa RM. Nifedipine versus tamsulosin for the management of lower ureteral stones. J Urol 2004;172:568–71. -Keshvary M, Taghavi R, Arab D. The effect of tamsulosin and nifedipine in facilitating juxtavesical stones’ passage. Med J Mashhad University Med Sci 2006;48:425–30.

  22. Side effects • Overall mild • Has resulted in minimal dropout in studies

  23. Summary • α-blockers and Nifedipine have been shown to have a clinically significant benefit in stone passage rates • Flomax appears to be superior to Nifedipine in time to passage and overall passage rates • MET works best for stones 5-10mm

  24. Questions?

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