Practical Management of Post-Irradiation Haemorrhagic Cystitis

							 Practical Management of Post-
Irradiation Haemorrhagic Cystitis

                JHL Tsu
          Division of Urology
Pamela Youde Nethersole Eastern Hospital
                     Background

• Haemorrhagic cystitis
      Acute or insidious onset diffuse bladder
       inflammation with haemorrhage


• Aetiologies
        Radiation
        Chemical eg. cyclophosphamide
        Viral infection
        Secondary bladder amyloidosis
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                       Incidence

• No uniformly quoted incidence in literature
      7-9% of patients with pelvic irradiation
                                      Ram Proc R Soc Med 1970



• Overall incidence G3-4 bladder toxicity
      RT to Ca prostate     2-9%
      RT to Ca cervix       2-5%
      RT to Ca bladder      2-12%


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                    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


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                  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
                                                      Haematuria
    poor compliance
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                    General Measures
                                                             Toomey

• General
    Resuscitation
    Transfusion
    Evacuation of clots
                                            Silver cannula
         • Manual (bedside)
         • Endoscopic (operating theatre)
         • Continuous NS bladder irrigation afterwards


• Often not enough to achieve haemostasis

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             Specific Treatment Options
                    1. Electrocautery

                  2. Intravesical therapy


                   3. Systemic therapy

                     4. Embolization

                        5. Surgery

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             Specific Treatment Options
                    1. Electrocautery

                  2. Intravesical therapy


                   3. Systemic therapy

                     4. Embolization

                        5. Surgery

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                   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

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             Specific Treatment Options
                    1. Electrocautery

                  2. Intravesical therapy


                   3. Systemic therapy

                     4. Embolization

                        5. Surgery

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             Specific Treatment Options


                  2. Intravesical therapy

       Hydrodistension              Formalin
        (Helmstein balloon)          Phenol
       Silver nitrate               Prostaglandins
       Alum                         Epsilon Amino
                                      Caproic Acid (EACA)

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                  Intravesical Silver Nitrate
• Silver Nitrate
      Organic salt that coagulates protein on contact,
       achieving haemostasis


• Efficacy : 68-70%           Jenkins J Urol 1986
                              Vijan J Urol 1988


• Toxicity
      Bilateral obstructive uropathy
      (Crystallisation of AgNO3 salt inside ureters)
                                                    Raghavaiah J Urol 1977
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                  Intravesical Silver Nitrate

Pros
      Well tolerated
      Local anaesthesia procedure at bedside


Cons
      Temporary haemostasis
      May need repeated instillations



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                  Intravesical Alum
• Alum
      Aluminium potassium sulfate
      Industrial chemical to purify
       water


• Reported efficacy :67-100%           Kennedy BJU 1986
                                       Arrizabalaga BJU 1987
                                       Goel J Urol 1985

• Mechanism
      Precipitates protein over bleeding vessels, causing
       vasoconstriction and haemostasis
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                     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

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                  Intravesical Formalin

• Formalin
      Industrial chemical as tissue
       fixative and embalming agent


• Efficacy : 80-92% complete haemostasis
                                          Brown Med J Aust 1969
                                          Kumar J Urol 1975
                                          Shah J Urol 1973
• Intravesical Formalin
      Cross-links proteins and precipitates it over
       mucosal surfaces, sealing off bleeding vessels
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                  Intravesical Formalin

• Toxicity
      75% major complications using 10% solution
      Minimal complications but similar efficacy using
       lower concentrations (1-2%)
                                          Fair Urology 1974
                                          Donahue J Urol 1989

      Minor : fever, dysuria
      Major : contracted bladder, vesico-ureteral reflux,
               ureteric stricture, vesico-vaginal fistula
                                           Donohue J Urol 1989


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                  Intravesical Formalin

Pros
      Most studied intravesical agent
      Time-tested method of haemostasis


Cons
      Requires anaesthesia
      Potentially severe complications
           • Mostly with 10% solution


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             Specific Treatment Options
                        1. Electrocautery

                      2. Intravesical therapy


                       3. Systemic therapy
                     iv Pentosanpolysulphate
                          oral Epsilon Amino
                      iv /4. Embolization
                      Caproic Acid (EACA)
                     iv Vasopressin
                            5. Surgery
                     Hyperbaric Oxygen (HBO)
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Hyperbaric Oxygen

• Delivery of 100%
  oxygen at hyperbaric
  condition (> 1 atm.)

• Mechanism
   Hyperbaria increases plasma O2 concentration
   Promotes angiogenesis, neovascularization and
    granulation into hypoxic tissue


 Efficacy : 82-100% complete response
                           Feldmeier Undersea Hyperb Med 2002
 JHSGR Sept 2006           Corman J Urol 2003, Bevers Lancet 1995
                  Hyperbaric Oxygen

Pros
      Alters pathophysiology of the disease
      No anaesthesia required


Cons
      Limited access
      Not suitable for critical patients
      Often prolonged treatment required

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             Specific Treatment Options
                    1. Electrocautery

                  2. Intravesical therapy


                   3. Systemic therapy

                     4. Embolization

                        5. Surgery

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                    Embolization
• Internal iliac artery embolization
      Efficacy : 90-92%
                              McIvor Clin Radiol 1982


Pros
      Local anaesthesia procedure

Cons
      Requires IR expertise
      Haematuria recurs when collateral develops
      Ischaemia and necrosis of pelvic organs, gluteus
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                            Surgery

• Surgical options
      Urinary diversion
           • Bilateral nephrostomies
           • Cutaneous ureterostomy
           • Ileal conduit


           Efficacy : 87.5% durable response
                                          Pomer BJU 1983


      Salvage cystectomy

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                         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



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   Agent          Mechanism              Pros            Cons                Cx
                                                     Anaesthesia,         Bladder
Electrocautery    Electric Cautery     Available
                                                     May not work        perforation
                                                                         Obstructive
   AgNO3         Chemical Cautery     Bedside, LA    Bleeding recurs
                                                                          uropathy

                                                     Contraindicated      Aluminium
    Alum         Chemical Cautery     Bedside, LA
                                                       in uraemia       toxicity, Death

                                                                           Bladder
                 Chemical Cautery,
  Formalin                              Effective     Anaesthesia      contracture…etc,
                   fixative effect
                                                                            Death
                                                                         Barotrauma,
    HBO          Neovascularization   Chamber, NA     Not available
                                                                        claustrophobia

                                                       Radiology           Bladder
Embolization         Ischaemia        XR suite, LA
                                                       expertise           necrosis

                 Urinary diversion
   Surgery                             Last resort    Anaesthesia           Death
                    Cystectomy
                    To bring home

• Post-irradiation haemorrhagic cystitis….

      A particularly difficult clinical problem of
       haemostasis for urologist

      …. the practical management of which involves…..




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    General measures      Usually fails

       Electrocautery     Haemostasis may not last

   Intravesical therapy   Works but beware of Cx

   Hyperbaric Oxygen      Not always available

       Embolization       Possible if radiologist around

           Surgery        Last resort
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                  Thank you




JHSGR Sept 2006