Renal and Genito-Urinary
Bladder
Childhood cancer survivors are at risk for hydronephrosis and bladder dysfunction.
Different treatment factors are responsible:
- Surgery
- Pelvic
- Central nervous system
- Radiation therapy (RT)
- Pelvic
- RT can cause spinal cord damage
- Chemotherapy
- alkylating agent
Problems can be:
- Severe:
- necessitating reconstructive surgery
- significant associated risk of renal failure
- Mild to moderately severe, but chronic and affecting the quality of life:
- urinary frequency and urgency
- incontinence
Hemorrhagic Cystitis (HC)
Irritation of the lining of the bladder leads to exposure of the submucosal blood vessels and bleeding.
Causes:
- Chemotherapy
- Oxazophorine alkylating agents
- Cyclophosphamide and ifosfamide
- Radiation therapy (RT) to the bladder
Patients who receive both chemotherapy and RT are at the highest risk
Chemotherapy related:
- Mediator of bladder injury in HC following cyclophosphamide chemotherapy is acrolein
- Acrolein:
- hepatic breakdown product of ifosfamide and cyclophosphamide
- excreted in the urine
- Most HC occurs acutely during cancer therapy, but can become chronic for as long as 20 years after completion of therapy
- Incidence of HC has been reported to be 15% in Ewing sarcoma patients treated with cyclophosphamide
Radiation related:
- Acute
- Chronic
- Due to endarteritis that leads to tissue hypoxia, ischemia, and necrosis.
- Associated with Radiation doses >30 Gy to the whole bladder or >60 Gy to a portion of the bladder
- Due to endarteritis that leads to tissue hypoxia, ischemia, and necrosis.
- Radiomimetic chemotherapeutic agents (such as the anti-tumor antibiotics dactinomycin and doxorubicin) in combination with RT may increase the risk
Symptoms:
HC is often painless, although patients may have:
- Urinary urgency
- Frequency
- Dysuria
- Suprapubic pain
- Occasional bladder spasms
Blood loss is variable and life-threatening hemorrhage very rare.
Infection with adenovirus or BK virus may contribute to the risk of HC.
Prevention:
Drugs that bind to acrolein and limit its damage:
- N-acetylcysteine (Mucomyst)
- 2-mercaptoethane sodium sulfonate (Mesna)
- Incidence of HC is decreased in patients whom receive mesna during cyclophosphamide therapy
- Mesna administration is now the standard of care for most pediatric cancer protocols utilizing high dose cyclophosphamide
Other methods used to prevent of treatment-induced HC:
- Vigorous hydration
- catheter drainage
- continuous bladder irrigation.
Bladder scarring and contraction:
The long term effect of scarring and fibrosis as a result of the primary tumor, surgery and RT is usually a small contracted bladder with decreased bladder capacity, reduced compliance and reduced contractility.
The etiology is most likely vascular ischemia (reduced blood supply) to the muscular wall.
RT contributes significantly to this damage. The bladder is far more likely to be severely scarred if the dose of RT is high and the great majority of the bladder was in the treatment field.
If the entire bladder receives 50 Gy then subsequent severe scarring, contraction and bladder dysfunction are very likely.
Scarring within the RT field with subsequent development of stricture can also affect the ureters and urethra.
