AUA 2010/2011 Guidelines for Diagnosis and Therapy of BPS/IC

1. AUA 2010/2011 Guidelinesfor Diagnosis and Therapy of BPS/IC • Primary approach: diet, physiotherapy, stress and life management

2. AUA 2010/2011 Guidelinesfor Diagnosis and Therapy of BPS/IC • Primary approach: diet, physiotherapy, stress and life management • first-line treatments include the oral medicines amitriptyline, hydroxyzine or cimetidine, pentosan polysulfate (Elmiron) and bladder instillation therapy.

3. AUA 2010/2011 Guidelinesfor Diagnosis and Therapy of BPS/IC • Primary approach: diet, physiotherapy, stress and life management • first-line treatments include the oral medicines amitriptyline, hydroxyzine or cimetidine, pentosan polysulfate (Elmiron) and bladder instillation therapy. • Pain management is important!

4. What happens in the BPS/IC bladder ??? TISSUE PERMEABILITY BARRIER URINE

5. BLADDER WALL STRUCTURE Small blue circles represent bound water molecules, and wavy lines represent the protein Backbone (core proteins). (Julius F. Metts, 2001).

6. Adrenergic system Intravesical vascular system C/P nervous system Urothelium PERMEABILITY GAG-LAYER

7. INSTILLATION THERAPY Heparin Hyaluronan Chondroitin Sulfate Pentosan Polysulfate DMSO Corticosteroids

8. HYALURONAN & Bladder Pain Syndrome 32 publications (9 Radiation cystitis, 6 rec.UTI)

9. HYALURONAN • GAG-Layer restitution • reduction of leukocytic and immunologic effects inside the bladder wall (via specific receptors) • improved tissue regeneration • neutralization of oxygen radicals (O2-) • suburothelial barrier 

10. MECHANISM OF HA THERAPY • In human bladder cell culture • inflammation induced by TNF-α • GAG-synthesis enhancement (p<0.05) • reduction of cytokines (IL-6, IGF-1) and histamine • original cell morphology maintained Hüther et al., Eur.Conference on Biomaterials, 2011

11. HYALURONAN THERAPY Morales, 1996 - 25 pts. / uncontrolled / 6 months - 71% improvement of symptoms Kallestrup, 2005 - 20 pts. / uncontrolled / 3 years - 65% improvement rate

12. Symptom improvement  2 (VAS) 126 patíents, modified potassium test + • (A) 87.4 % after instillation therapy • (B) 82.5 % confirmed benefit for QOL • average 11.6 instillations • > 50 % no need for further therapy! Riedl et al. Int.J.Urogynecol., 2008

13. A positive modified potassium test identifies a group of BPS/IC patients that has a > 80 % chance of symptom remission / improvement with GAG substitution therapy. To our experience, patients with negative test do rarely benefit from GAG substitution.

14. Long-term efficacy of hyaluronan instillation therapy in BPS/IC 45/70 pts. evaluated after an average of 5 years post instillation therapy pretherapeutic VAS 8,22 Posttherapeutic VAS 3,93 VAS 5 years later 2,34 Complete Symptom Remission 50% (22/45) Stable Disease with HA Maintenance 33% (17/45) No Success 17% (6/45) Engelhart, P.F., Morakis, N., Riedl, C.R.: Syndrom/Interstitieller Zystitis (BPS/IC). Int.Urogynecol.J.., 2011

15. Long-term efficacy of hyaluronan instillation therapy in BPS/IC • With intravesical hyaluronan therapy, besides a high initial response rate, > 50% stay of patients free of symptoms for 5 years and longer (no additional therapy necessary) • One third of patients needs maintenance of hyaluronan instillations in a monthly schedule to stay free of symptoms Engelhart, P.F., Morakis, N., Riedl, C.R.: Jint.Urolgynecol.J.., 2011

16. GAG-SUBSTITUTION THERAPY IN BPS/IC - BASICS • Instillation times > 2 hours • Hydrophilic catheters • Antibiotic prophylaxis on instillation days • (e.g.Nitrofurantoin 50 mg) • STD exclusion (20% ureaplasma infections in IC patients!) • VAS Score for documentation of treatment success • No abrupt termination of instillation • -extension of instillations intervals (2-3-4 weeks)

17. How to test the urine-tissue-barrier ???

18. I am a Potassionist Modified potassium testing gives the advantage of identifying vesical reactions beyond the purely mechanistic effects of bladder distension

19. Original & Modified PST

20. Modified Potassium Test = Comparative Assessment of Maximal Bladder Capacity > 30 % Urgency BPS/IC patients NaCl 0.9% 0.2M KCl Daha, Riedl et al., J.Urol.2003

21. Modified Potassium Test = Comparative Assessment of Maximal Bladder Capacity Normal controls NaCl 0.9% 0.2M KCl Daha, Riedl et al., J.Urol.2003

22. Modified Potassium Test

23. MODIFIED POTASSIUM TEST EVALUATION OF URINE-TISSUE- BARRIER-DYSFUNCTION TISSUE PERMEABILITY URINE Increased potassium sensitivity is a consequence to simple or complex dysfunction of urothelium, intravesical vascular system, adrenergic system and neuronal structures

24. THE MODIFIED POTASSIUM TEST IN CLINICAL PRACTICE: RESULTS

25. A positive modified potassium test does not indicate BPS/IC or an isolated GAG-deficiency, but rather is a sign for simple or complex dysfunction of the urine-tissue barrier, that is commonly found in BPS/IC patients and may be cured by GAG substitution.

26. Posttherapeutic Changes in theModified Potassium Test ?L.K.Daha, C.Riedl

27. 23 Patients 13 Responders 10 Nonresponders

28. Results of the visual analogue scale symptom score (0 – 10)

29. Results of comparative assessment of maximal bladder capacity with 0.9% NaCl and 0.2 M KCl before and after GAG substitution therapy Bladder capacity NaCl NaCl KCl KCl Daha et al., Scand J.Urol.2008

30. CISTIC