CUA BPR 2019: Pediatric hemorrhagic cystitis

Question 1

What is the most common cause of hemorrhagic cystitis in children?

Answer 1

Immediate and late effects of stem cell and or bone marrow transplantation for malignant and benign diseases
rare causes: resperidone, ataxia telangectasia

Question 2

what are chemotherapy agents implicated in causing HC?

Answer 2

alkylating agents( cyclophosphamide, ifosfamide, busulfan) bc they yield acrolein( causes bladder mucosal inflammation sloughing and thinning)

Question 3

What is the cause of late onset HC?

Answer 3

immune related, reactivation of BKV(most common) , CMV, JC, adenovrius, SV40

Question 4

what are some risk factors for HC?

Answer 4

allogenic transplant, conditioning regiment(alkylating agent), XRT, development of acute GVHD, CMV reactivations, age less than 5 protective

Question 5

what are some preventative measures for HC?

Answer 5

1) hyperhydration/forced diuresis
2) CBI( start prior to chemo and continue for 48 hours after)
3) Mesna
4) Pain control
5) bladder spasm management
6) hematological optimization ( transfusion if indicated)

Question 6

how does mesna work

Answer 6

deactivates acolein through binding of mesna with it, it is given IV.

Question 7

What is recommended for patients who are proven to have a positive urine viral culture or PCR as cause of HC?

Answer 7

treatment with IV or intravesical antivirals is recommended as a relatively low-risk treatment (cidofovir), leflunomide–> to treat BKV, ribavarin–> adenovirus

Question 8

what is the mechanism of action of pentosan polysulfate?

Answer 8

PPS is semisynthetic glycosaminoglycan, its proposed mechanism of action is through adherence to the bladder wall glcyosaminoglycan layer and replacement of already damaged areas in order to protect bladder from irritants.

Question 9

What is the recommendation for PPS?

Answer 9

it is given oral, there is limited evidence on its positive benefits, more studies are needed but there is some evidence.

Question 10

what are non-invasive options for management of Grade I-II HC?

Answer 10

PPS, Estrogen, antivirals, hyperbaric oxygen therapy

Question 11

what are invasive options for management of grade I-II HC?

Answer 11

intravesical Alum, hyaluronic acid, PGE, Antivirals

Question 12

what is the recommendations re estrogen?

Answer 12

There is conflicting evidence regarding benefit vs harm, additional studies are needed.

Question 13

how does hyperbaric oxygen therapy help with HC>

Answer 13

It is thought to assist in the resolution of HC by inducing neovascularity and permanent tissue healing in the damaged bladder tissue

Question 14

HOT has been proven to be safe, effective,
and relatively low-risk in treating pediatric patients
with HC. Its widespread use, however, may be limited due to cost and access to facilities with HOT

Answer 14

YES correct, HOT= hyperbaric oxygen therapy

Question 15

what is the initial recommended treatment for high grade (III-IV) HC?

Answer 15

cysto clot evac followed by

• fulguration, fibrin glue, intravesical irrigation
• or intravesical irrigation(diffuse bleeding), formalin

Question 16

What is the treatment for high grade refractory pediatric HC?

Answer 16

Stable patient:
- PNTs(Nephrostomy tubes) , Vesicostomy +/- packing, cystectomy
Unstable
- selective angioembolization 
- PNTs

Question 17

What is recommended regarding use of PGE1/2 for management of HC?

Answer 17

PGs (prostaglandins) may be of modest benefit as an
intravesical therapy in pediatric patients with HC with urethral catheters, although additional studies are needed to clarify its efficacy and if sedation or general anesthesia is needed to administer the therapy due to concerns for its potential to cause painful bladder spasms

Question 18

Can hyaluronic acid be used in management of HC?

Answer 18

yes, HA intravesical therapy may be of benefit in treating HC via bladder instillation, although repeated applications may be required and, thus, more robust evidence is required to demonstrate its efficacy

Question 19

how does alum work?

Answer 19

Alum is thought to work by adhering to raw protein surfaces, resulting in decreased vascular permeability, vasoconstriction, and reduced inflammation

Question 20

what is recommended regarding use of alum in HC?

Answer 20

Alum bladder irrigation is effective in treating pediatric HC, although the patient’s bladder must be fully cleared of blood clots prior to initiation of therapy. Patients must also be monitored closely for potential aluminum toxicity, particularly in the setting of renal failure

Question 21

what is recommended regarding use of cystoscopy+ fulguration for management of HC?

Answer 21

cystoscopy, clot evacuation, and fulguration of bleeding are a mainstay of therapy in management of pediatric HC for their capacity to diagnose and treat HC, as well as provide symptom relief from patients in clot retention( as mentioned earlier particularly for grade III, IV)

Question 22

What is recommended regarding use of fibrin glue for HC?

Answer 22

in the studies they used 24-F scope, wont be able to fit that in most kids, no CBI post application. Intravesical fibrin glue application is a promising treatment option in patients undergoing cystoscopy with clot evacuation, as it can be applied focally or diffusely to hemorrhagic areas. Additional research is needed to expand its applicability, as current recommendations for large-caliber cystoscopes limits its use in children

Question 23

what is the mechanism of action of formalin?

Answer 23

The proposed mechanism of action of formalin, much like its derivative formaldehyde, is to precipitate proteins by reducing amino acids and fixing blood vessels, thus achieving hemostasis

Question 24

what is the recommendation for use of formalin or silver nitrate in pediatric HC>

Answer 24

Although effective, the need for anesthesia
with formalin instillation and the potential long-term
compromise of bladder function must be heavily considered when resorting to this therapeutic option for children with HC. 1,2,4% use have been reported in kids, do VCUG to rule out reflux, if reflux present use flugratty catheters to obstruct upper tracts

Question 25

what is the rationale for using NTs in management of HC>

Answer 25

other than improving renal function they think urokinase bathes the bladder wall and clot and prevents hemostasis by breaking up fibrin( it is fibrinolytic) so by diverting it you just let it clot off.

Question 26

SVAE offers modest control of HC refractory to conservative therapy, however, outside of unstable patients, the appropriate time point for its use along the HC treatment pathway and the long-term safety of its application require further investigation

Answer 26

YES

SVAE: supra-selective bilateral vesical artery embolization

Question 27

what is recommended regarding use of cutaneous vesicostomy in pediatric HC population ?

Answer 27

Despite a lack of high-quality studies, cutaneous vesicostomy in the terminal or refractory pediatric patient offers potentially reversible direct bladder access for clot evacuation and application of topical therapies, while also allowing for possible removal of painful urethral catheters

Question 28

what is the last line in management of HC patient who is somewhat stable?

Answer 28

Cystectomy is reserved as a treatment option when all other efforts to control HC have failed. Long-term implications of this option must be considered in the pediatric population, as well as the fitness and hemodynamic stability of the patient for whom it is chosen

Question 29

Due to the experimental nature of therapies such as recombinant human keratinocyte growth factor, epidermal growth factor, placenta-derived stromal cells, adoptive transfer of viral-specific T cells, factor VII, factor XIII, and mesenchymal stem cells, their therapeutic use to treat HC is not recommended until further robust trials demonstrate safety and benefit

Answer 29

CORRECT