Discussion
Our patient developed grade 3 CTCAE HC, which resolved completely with
supportive care. Chemotherapy-induced HC generally resolves upon
withdrawal of the offending agent, along with the treatments described
above. It has a favourable prognosis when compared to HC caused by
pelvic radiotherapy, which can recur for many months post-treatment.
Complications are rare in chemical-induced HC but can include acute
kidney injury requiring dialysis, urinary tract obstruction/infection,
bladder perforation and death4. Long-term effects
include bladder and upper tract fibrosis as well as reduced bladder
capacity. In paediatric patients, increased mortality is linked to
catheterisation, need for dialysis and presence of
BKV9.
Infective agents were ruled out in this case. Urine culture was negative
with no evidence of pus or white cells/organisms on microscopy. The
absence of pyuria has a negative predictive value of near
90%11. BKV, adenovirus and CMV have been implicated
in the pathogenesis of HC12,13 and serology for all
was negative.
Pelvic radiotherapy is a known cause of HC. Proton beam therapy, which
is increasingly used for medulloblastoma in a paediatric population,
allows for more precise treatment than traditional photon radiotherapy
due to the Bragg peak phenomenon14 and therefore
reduces the damage done to adjacent organs and tissues. Craniospinal
irradiation is carried out to the level of L1 vertebrae and is therefore
sufficiently removed from the bladder to rule out. There is no evidence
in the literature that HC can be caused by distant radiotherapy.
A literature review regarding each of the medications the patient was
taking (levomepromazine, omeprazole, ondansetron and paracetamol)
revealed one unrelated result when searched with HC on Pubmed.
Accidental administration of cyclophosphamide was excluded after
thorough investigation by pharmacy and nursing staff.
It is possible that the chemotherapy agents the patient received before
HC developed are culprits. Vincristine is mostly hepatically
metabolised15 and is commonly used in many
chemotherapeutic regimes and is therefore unlikely to be the cause.
Lomustine is metabolised renally, but does not typically cause any renal
issues, unless used for a prolonged period16.
Cisplatin is a platinum-based alkylating agent used for many
malignancies and is well documented to cause nephrotoxicity due to
accumulation in renal tubules17. The co-transporter
protein OCT-2 has been identified as a key protein for the uptake of
cisplatin into renal cells, and cisplatin competitively inhibits other
substrates that are normally taken up via OCT-2. Inside the cell, there
are a myriad of mechanisms whereby cisplatin can cause
apoptosis/necrosis of the cell, including upregulation of
p5318. OCT-2 receptors are also found in the
urothelium19, so it follows that cisplatin could be
taken up in a similar way in the bladder and cause inflammation and
necrosis, leading to HC. In addition, carboplatin, a similar akylating
agent, which can be substituted with cisplatin in the CCLG treatment
guideline, has been mentioned in one paper as a potential
cause3. Another case reports HC following combination
chemotherapy with bleomycin, vinblastine, cisplatin and
etoposide20.
Given the number of causes for HC, it is possible that cisplatin-induced
HC has been underreported. Adenovirus is common among the general
population and it is not hard to imagine a rare patient with
cisplatin-induced HC being co-infected with adenovirus and the condition
being falsely attributed to the known cause.