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JHL Tsu Division of Urology Pamela Youde Nethersole Eastern Hospital. Practical Management of Post-Irradiation Haemorrhagic Cystitis. Background. Haemorrhagic cystitis Acute or insidious onset diffuse bladder inflammation with haemorrhage Aetiologies Radiation Chemical eg. cyclophosphamide

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jhl tsu division of urology pamela youde nethersole eastern hospital

JHL TsuDivision of UrologyPamela Youde Nethersole Eastern Hospital

Practical Management of Post-Irradiation Haemorrhagic Cystitis

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

radiotherapy
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
slide5

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

general measures
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

specific treatment options
Specific Treatment Options

1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

specific treatment options1
Specific Treatment Options

1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

electrocautery
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
specific treatment options2
Specific Treatment Options

1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

specific treatment options3
Hydrodistension (Helmstein balloon)

Silver nitrate

Alum

Formalin

Phenol

Prostaglandins

Epsilon Amino Caproic Acid (EACA)

Specific Treatment Options

2. Intravesical therapy

intravesical silver nitrate
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

intravesical silver nitrate1
Intravesical Silver Nitrate

Pros

  • Well tolerated
  • Local anaesthesia procedure at bedside

Cons

  • Temporary haemostasis
  • May need repeated instillations
intravesical alum
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

intravesical alum1
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

intravesical formalin
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

intravesical formalin1
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

intravesical formalin2
Intravesical Formalin

Pros

  • Most studied intravesical agent
  • Time-tested method of haemostasis

Cons

  • Requires anaesthesia
  • Potentially severe complications
    • Mostly with 10% solution
specific treatment options4
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

hyperbaric oxygen
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

hyperbaric oxygen1
Hyperbaric Oxygen

Pros

  • Alters pathophysiology of the disease
  • No anaesthesia required

Cons

  • Limited access
  • Not suitable for critical patients
  • Often prolonged treatment required
specific treatment options5
Specific Treatment Options

1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

e mbolization
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

surgery
Surgery
  • Surgical options
    • Urinary diversion
      • Bilateral nephrostomies
      • Cutaneous ureterostomy
      • Ileal conduit

Efficacy : 87.5% durable response

    • Salvage cystectomy

Pomer BJU 1983

surgery1
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
to bring home
To bring home
  • Post-irradiation haemorrhagic cystitis….
    • A particularly difficult clinical problem of haemostasis for urologist
    • …. the practical management of which involves…..
slide28

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

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