JHL Tsu Division of Urology Pamela Youde Nethersole Eastern Hospital

1. JHL TsuDivision of UrologyPamela Youde Nethersole Eastern Hospital Practical Management of Post-Irradiation Haemorrhagic Cystitis

2. Background • Haemorrhagic cystitis • Acute or insidious onset diffuse bladder inflammation with haemorrhage • Aetiologies • Radiation • Chemical eg. cyclophosphamide • Viral infection • Secondary bladder amyloidosis

3. Incidence • No uniformly quoted incidence in literature • 7-9% of patients with pelvic irradiation • Overall incidence G3-4 bladder toxicity • RT to Ca prostate 2-9% • RT to Ca cervix 2-5% • RT to Ca bladder 2-12% Ram Proc R Soc Med 1970

4. Radiotherapy • Used in primary, adjuvant or palliative setting for various pelvic malignancies • Urinary bladder is irradiated • Intentionally eg. Ca bladder • Incidentally eg. Ca prostate, Ca cervix

5. Radiation induced endothelial damage Subendothelial intimal proliferation Endarteritis obliterans Ischaemia to mucosa and detrusor Focal / diffuse ischaemic necrosis Chronically hypoxic mucosa Progressive fibroblast proliferation in submucosa & detrusor Ulceration & poor healing Contracted bladder with poor compliance Haematuria

6. General Measures Toomey • General • Resuscitation • Transfusion • Evacuation of clots • Manual (bedside) • Endoscopic (operating theatre) • Continuous NS bladder irrigation afterwards • Often not enough to achieve haemostasis Silver cannula

7. Specific Treatment Options 1. Electrocautery 2. Intravesical therapy 3. Systemic therapy 4. Embolization 5. Surgery

8. Specific Treatment Options 1. Electrocautery 2. Intravesical therapy 3. Systemic therapy 4. Embolization 5. Surgery

9. Electrocautery • Achieves haemostasis cystoscopically • First line of treatment Pros • Can be done right after cystoscopic clot evacuation Cons • Often not possible due to diffuse bleeding

10. Specific Treatment Options 1. Electrocautery 2. Intravesical therapy 3. Systemic therapy 4. Embolization 5. Surgery

11. Hydrodistension (Helmstein balloon) Silver nitrate Alum Formalin Phenol Prostaglandins Epsilon Amino Caproic Acid (EACA) Specific Treatment Options 2. Intravesical therapy

12. Intravesical Silver Nitrate • Silver Nitrate • Organic salt that coagulates protein on contact, achieving haemostasis • Efficacy : 68-70% • Toxicity • Bilateral obstructive uropathy • (Crystallisation of AgNO3 salt inside ureters) Jenkins J Urol 1986 Vijan J Urol 1988 Raghavaiah J Urol 1977

13. Intravesical Silver Nitrate Pros • Well tolerated • Local anaesthesia procedure at bedside Cons • Temporary haemostasis • May need repeated instillations

14. Intravesical Alum • Alum • Aluminium potassium sulfate • Industrial chemical to purify water • Reported efficacy :67-100% • Mechanism • Precipitates protein over bleeding vessels, causing vasoconstriction and haemostasis Kennedy BJU 1986 Arrizabalaga BJU 1987 Goel J Urol 1985

15. Intravesical Alum Pros • Relatively well tolerated • Can be instillated under local anaesthesia Toxicity • Aluminium toxicity • Manifested as obtundation, encephalopathy, seizure • Systemic absorption in patients with renal impairment • 2 deaths attributed to this Kavoussi J Urol 1986 Modi Am J Kidney Dis 1988 Seear Urology 1990

16. Intravesical Formalin • Formalin • Industrial chemical as tissue fixative and embalming agent • Efficacy : 80-92% complete haemostasis • Intravesical Formalin • Cross-links proteins and precipitates it over mucosal surfaces, sealing off bleeding vessels Brown Med J Aust 1969 Kumar J Urol 1975 Shah J Urol 1973

17. Intravesical Formalin • Toxicity • 75% major complications using 10% solution • Minimal complications but similar efficacy using lower concentrations (1-2%) • Minor : fever, dysuria • Major : contracted bladder, vesico-ureteral reflux, ureteric stricture, vesico-vaginal fistula Fair Urology 1974 Donahue J Urol 1989 Donohue J Urol 1989

18. Intravesical Formalin Pros • Most studied intravesical agent • Time-tested method of haemostasis Cons • Requires anaesthesia • Potentially severe complications • Mostly with 10% solution

19. Specific Treatment Options 1. Electrocautery • iv Pentosanpolysulphate • iv / oral Epsilon Amino Caproic Acid (EACA) • iv Vasopressin • Hyperbaric Oxygen (HBO) 2. Intravesical therapy 3. Systemic therapy 4. Embolization 5. Surgery

20. Hyperbaric Oxygen • Delivery of 100% oxygen at hyperbaric condition (> 1 atm.) • Mechanism • Hyperbaria increases plasma O2 concentration • Promotesangiogenesis, neovascularization and granulation into hypoxic tissue • Efficacy : 82-100% complete response Feldmeier Undersea Hyperb Med 2002 Corman J Urol 2003, Bevers Lancet 1995

21. Hyperbaric Oxygen Pros • Alters pathophysiology of the disease • No anaesthesia required Cons • Limited access • Not suitable for critical patients • Often prolonged treatment required

22. Specific Treatment Options 1. Electrocautery 2. Intravesical therapy 3. Systemic therapy 4. Embolization 5. Surgery

23. Embolization • Internal iliac artery embolization • Efficacy : 90-92% Pros • Local anaesthesia procedure Cons • Requires IR expertise • Haematuria recurs when collateral develops • Ischaemia and necrosis of pelvic organs, gluteus McIvor Clin Radiol 1982

24. Surgery • Surgical options • Urinary diversion • Bilateral nephrostomies • Cutaneous ureterostomy • Ileal conduit Efficacy : 87.5% durable response • Salvage cystectomy Pomer BJU 1983

25. Surgery Pros • Last resort when all else fails Cons • May not be feasible as patient too ill already • Significant complication rates • High perioperative mortality rate

27. To bring home • Post-irradiation haemorrhagic cystitis…. • A particularly difficult clinical problem of haemostasis for urologist • …. the practical management of which involves…..

28. General measures Usually fails Haemostasis may not last Works but beware of Cx Not always available Possible if radiologist around Last resort Electrocautery Intravesical therapy Hyperbaric Oxygen Embolization Surgery

29. Thank you