Radiation Cystitis - Role Radiation Cystitis - Role of Minimally invasive of Minimally invasive

Procedures Procedures JHGR 15/9/2007JHGR 15/9/2007

UCHUCHChau Hin LysanderChau Hin Lysander

Case ScenarioCase Scenario

• 65/F65/F• HT, DM with renal impairmentHT, DM with renal impairment• Ca cervix with THSBO + RTCa cervix with THSBO + RT• History of intestinal obstruction with small History of intestinal obstruction with small

bowel resection donebowel resection done• Presented with RT cystitis with recurrent aPresented with RT cystitis with recurrent a

dmission due to haematuria dmission due to haematuria

Incidence of intractable haematuriaIncidence of intractable haematuria

• Reported as 6.5% in a series of 1784 patients with carcinoma of the cervix treated with both intracavitary and external beam radiotherapy

• Median interval to developing haematuria after completing therapy was 35.5 months.

Levenback C, Gynecologic Oncol 1994; 55: 206–10

• 3-5% for prostate cancer with RT

Choong SKS, BJU Int 2000; 86: 951–9

Pathogenesis Pathogenesis • Chronic phase of the radiation-induced submucosal dam

age:– Necrosis of the vascular endothelium– Vessel wall thickening – Obliterative endarteritis

• Hypoxia, hypovascularity and ischaemia.

• Neovascularization which are fragile and prone to bleed

Stewart FA, Br J Cancer 1986; 7 (Suppl): 280–91

Initial ManagementInitial Management

• Resusicitation +/- blood transfusion• Clot evacuation and continuous bladder irrig

ation • Diathermy coagulation

– Excellent immediate results– High recurrence rate– More ischaemia => more neovascularization

Definitive ManagementDefinitive Management

• Cystectomy and urinary diversion– Major operation for benign condition– Major impact to patient’s QOL– Co-morbidities limitation

Any things we can do before that?

Treatment optionsTreatment options• Intravesical alum irrigation• Hyperbaric oxygen for radiation cystitis• Embolization• Sodium pentosanpolysulphate• Endoscopic laser/argon beam coagulation

• Intravesical formalin• Hydrostatic pressure• ………

Choong SKS, BJU Int 2000; 86: 951–9

Intravesical alum irrigationIntravesical alum irrigation• First introduced by Floyd Csir to Ostroff and Chenault in 1982

Ostroff EB, J Urol 1982; 128: 929–30

• Alum (either aluminium ammonium sulphate or aluminium potassium sulphate)

• Reduced capillary permeability, contraction of intercellular space, vasoconstriction, hardening of the capillary endothelium and a reduction in oedema, inflammation and exudate

Arrizabalaga M, Br J Urol 1987; 60: 223–6

• Using a 1% alum solution; 50 g of alum is dissolved in 5 L sterile water and used to irrigate the bladder at 250–300 mL/h

• Bleeding stopped within 4 days and well tolerated

Kennedy C, Br J Urol 1984; 56: 673–5

Hyperbaric oxygen therapyHyperbaric oxygen therapy

• First described in the 1980s

Bevers RFM, Lancet 1995; 346: 803–5

• The rationale of hyperbaric oxygen treatment is to reverse the vascular radiation-induced pathophysiology through increased oxygen tension

Noordzij JW, Int Urogynecol J 1993; 4: 160–7Kindwall EP, Clin Plast Surg 1993; 20: 589–92

• Prospective study • 40 patients with biopsy-confirmed radiation cystitis and severe

haematuria

• Results:– 30 (75%) had no haematuria for at least 3 months after hyperbaric oxyg

en therapy– 7 (17%) had occasional slight haematuria – 3 (7.5%) did not respond to the treatment– The recurrence rate was 0.12%/year– The bladder was preserved (cystectomy avoided) in 36 patients (90%)

Bevers RFM, Lancet 1995; 346: 803–5

Short term resultsShort term results

Long term resultsLong term results

• 11 patients treated with 28–64 HBO treatments

• Mean follow up of 5.1 years. • 8/11 patients were asymptomatic with mea

n follow-up of 2.5 years

Del Pizzo, J Urol 1998; 160: 731–3

• Cystoscopy after hyperbaric oxygen therapy showed a decrease in haemorrhagic sites and telangiectasias

Rijkmans BG, Eur Urol 1989; 16: 354–6

““Potential side-effects caused by barometric pressure changes or toxicity may Potential side-effects caused by barometric pressure changes or toxicity may be associated with hyperbaric oxygen treatment, but be associated with hyperbaric oxygen treatment, but serious complications serious complications such as CNS toxicity and decompression sickness are clinically rare in such such as CNS toxicity and decompression sickness are clinically rare in such low-pressure and brief oxygen-inhalation treatments”low-pressure and brief oxygen-inhalation treatments”

Neheman A, BJU International. 96(1)(pp 107-109), 2005

EmbolizationEmbolization• Therapeutic embolization for the control of bla

dder haemorrhage was first reported in 1974 by Hald and Mygiand

Hald T, J Urol 1974; 112: 60–3

• Therapeutic embolization has been achieved by completely occluding the internal iliac artery with blood clot, Tachotop™, Gelfoam™, Histoacryl™ or isobutyl-2-cyanoacrylate

ComplicationsComplications

• Gluteal pain (the commonest)• Gangrene of the bladder • Neurological defect affecting one or both l

ower limbs

Selective EmbolizationSelective Embolization

• To embolize the superior and inferior vesical arteries with Gelfoam on one side, after catheterizing from the ipsilateral femoral artery

Kobayashi T, Radiology 1980; 136: 345–8

• At 12-months follow-up, cystoscopy demonstrated the disappearance of all teleangectatic dilatations, with perfect resolution of the clinical pattern. (Case report)

De Berardinis E, International Journal of Urology. 12(5):503-5, 2005 May.

Superior vesical artery

Inferior vesical artery

Pre-embolization: increased vascularity in the pelvic area

Post-embolization

Oral sodium pentosanpolysulphateOral sodium pentosanpolysulphate

• Exact mechanism unknown• SPP replaces surface glycosaminoglycans

and reverses the damage to the surface• 51/60 patients • Duration of treatment 180 days• Mean interval between completing treatme

nt and developing haematuria was 4.5years

Sandhu S.S., BJU International. 94(6)(pp 845-847),

Endoscopic laser coagulationEndoscopic laser coagulation• LA • Neodymium:YAG laser• 39 patients received one session• 2 patients received two sessions

• Results:– No complication– Recurrence of bleeding not seen at a mean follow-up

period of 14 months

Ravi R, Lasers Surg Med 1994; 14: 83–7

Argon-beam coagulatorArgon-beam coagulator

• 7 patients with radiation cystitis• 6 received one session• Successfully treated with mean follow up

of 15 months

Wines MP, BJU International. 98(3):610-2, 2006 Sep

DiscussionDiscussion

• Denton AS reviewed all non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis.

• Cochrane Database of Systematic Reviews. (3):CD001773, 2002.

Among 79 studies……Among 79 studies……• 2 RCTs but excluded as they addressed the treat

ment or prevention of acute radiation cystitis

• 2 studies were controlled but not randomised

• 3 prospective case series and 59 retrospective case series only mentioned briefly in the results section. No detailed analysis. Not randomised or controlled.

• The remainder were reviews

• Studies were graded according to the criteria used by the NHS executive for quality of research

• Most are level IIC and level IIIC evidence

ConclusionsConclusions

• There may be difficulties in identifying enough cases to participate in a randomised controlled trial

• Although the results were impressive, it is of a low level of evidence to influence current trends in clinical practice

• Selection of treatment options should be based on availability, toxicity and surgeon’s preferrence

The EndThe EndThank YouThank You