Practical Management of Post-Practical Management of Post-Irradiation Haemorrhagic Irradiation Haemorrhagic

CystitisCystitisJHL TsuJHL Tsu

Division of UrologyDivision of UrologyPamela Youde Nethersole Eastern HospitalPamela Youde Nethersole Eastern Hospital

JHSGR Sept 2006

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

• 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

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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

Progressive fibroblast proliferationin submucosa & detrusor

Chronically hypoxic mucosa

Contracted bladder withpoor compliance

Haematuria

Ulceration & poor healing

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General Measures

• General Resuscitation Transfusion Evacuation of clots

• Manual (bedside)• Endoscopic (operating theatre)• Continuous NS bladder irrigation afterwards

• Often not enough to achieve haemostasis

Silver cannula

Toomey

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1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

Specific Treatment Options

JHSGR Sept 2006

1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

Specific Treatment Options

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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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1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

Specific Treatment Options

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2. Intravesical therapy

Specific Treatment Options

Hydrodistension (Helmstein balloon)

Silver nitrate Alum

Formalin Phenol Prostaglandins 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%

• Toxicity Bilateral obstructive uropathy (Crystallisation of AgNO3 salt inside ureters)

Jenkins J Urol 1986Vijan J Urol 1988

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%

• Mechanism Precipitates protein over bleeding vessels,

causing vasoconstriction and haemostasis

Kennedy BJU 1986Arrizabalaga BJU 1987Goel J Urol 1985

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Intravesical AlumPros

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

• Intravesical Formalin Cross-links proteins and precipitates it over

mucosal surfaces, sealing off bleeding vessels

Brown Med J Aust 1969Kumar J Urol 1975

Shah J Urol 1973

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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 1974Donahue J Urol 1989

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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1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

Specific Treatment Options

iv Pentosanpolysulphate iv / oral Epsilon Amino

Caproic Acid (EACA) iv Vasopressin 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 2002Corman J Urol 2003, Bevers Lancet

1995

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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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1. Electrocautery

2. Intravesical therapy

3. Systemic therapy

4. Embolization

5. Surgery

Specific Treatment Options

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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

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Surgery

• Surgical options Urinary diversion

• Bilateral nephrostomies• Cutaneous ureterostomy• Ileal conduit

Efficacy : 87.5% durable response

Salvage cystectomy

Pomer BJU 1983

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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

Agent Mechanism Pros Cons CxElectrocaute

ryElectric Cautery Available

Anaesthesia, May not work

Bladder perforation

AgNO3Chemical Cautery

Bedside, LABleeding recurs

Obstructive uropathy

AlumChemical Cautery

Bedside, LAContraindicated in uraemia

Aluminium toxicity, Death

FormalinChemical

Cautery, fixative effect

Effective AnaesthesiaBladder

contracture…etc, Death

HBONeovascularizati

onChamber, NA Not available

Barotrauma, claustrophobi

a

Embolization

Ischaemia XR suite, LARadiology expertise

Bladder necrosis

SurgeryUrinary

diversion Cystectomy

Last resort Anaesthesia Death

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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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Electrocautery

Intravesical therapy

Hyperbaric Oxygen

Embolization

Surgery

Usually fails

Haemostasis may not last

Works but beware of Cx

Not always available

Possible if radiologist around

Last resort

General measures

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Thank you