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Intravesical instillation of high molecular weight sodium hyaluronate in radiation-induced cystitis: a prospective pilot study

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World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

To assess the efficacy and safety of intravesical instillation of high molecular weight sodium hyaluronate (HMW-HA) for the treatment of radiation-induced cystitis.

Methods

This prospective cohort study was conducted in seven centers in France. Eligible patients with radiation-induced cystitis were recruited between April 2020 and March 2021. A sterile disposable 50 ml prefilled solution containing 0.16% (80 mg/50 mL) HMW-HA (INSTYLAN) was instilled weekly into the bladder. The treatment consisted of 6 sessions (V1 to V6). Outcomes were assessed 1 week (V7) and 4 weeks (V8) after the last session and were compared with baseline (V0). The primary endpoint was bladder pain, evaluated by a Questionnaire with 5 closed-ended response options. Secondary endpoints included changes from baseline for hematuria, urinary frequency, and the effect of urgencies on Quality of Life (QoL). Adverse events (AEs) were graded according to the CTCAE 3.0 classification.

Results

A total of 30 participants were enrolled. The Intent-to-Treat analysis showed a significant reduction in pelvic pain intensity (− 45.81%, p < 0.001), hematuria (− 26.87%, p = 0.008), total 24 h voids (− 23.92%, p < 0.001) and the effect of urgencies on QoL (− 33.92%, p < 0.001) at V7. The improvement for each outcome remained stable during the post-therapeutic period between V7 and V8. Bladder instillation therapy was well-tolerated: two treatment-related AEs (6.6%) were reported corresponding to two grade 1 hematuria.

Conclusions

Intravesical instillation of HMW-HA appears to be effective in the treatment of radiation-induced cystitis. Further comparative studies with longer follow-up are needed to confirm our preliminary results.

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Availability of data and materials

Data are available upon request to the corresponding author.

Code availability

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References

  1. Matz EL, Hsieh MH (2017) Review of advances in uroprotective agents for cyclophosphamide- and ifosfamide-induced hemorrhagic cystitis. Urology 100:16–19

    Article  Google Scholar 

  2. Payne H, Adamson A, Bahl A et al (2013) Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. BJU Int 112:885

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Fransson P, Widmark A (1999) Late side effects unchanged 4–8 years after radiotherapy for prostate carcinoma: a comparison with age-matched controls. Cancer 85:678–688

    Article  CAS  Google Scholar 

  4. Mendenhall WM, Henderson RH, Costa JA et al (2015) Hemorrhagic radiation cystitis. Am J Clin Oncol 38(3):331–336

    Article  CAS  Google Scholar 

  5. Ribeiro de Oliveira TM, Carmelo Romao AJ, Gamito Guerreiro FM, Matos Lopes TM (2015) Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. Int J Urol 22:962–966

    Article  CAS  Google Scholar 

  6. Oscarsson N, Müller B, Rosén A et al (2019) Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial. Lancet Oncol 20(11):1602–1614

    Article  Google Scholar 

  7. Zwaans BM, Chancellor MB, Lamb LE (2016) Modeling and treatment of radiation cystitis. Urology 88:14–21

    Article  Google Scholar 

  8. Browne CD, Davis NF, Mac Craith E et al (2015) A narrative review on the pathophysiology and management for radiation cystitis. Adv Urol 2015:346812

    Article  CAS  Google Scholar 

  9. Pascoe C, Duncan C, Lamb BW et al (2019) Current management of radiation cystitis: a review and practical guide to clinical management. BJU Int 123(4):585–594

    Article  Google Scholar 

  10. Shao Y, Lu GL, Shen ZJ (2012) Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis. BJU Int 109(5):691–694

    Article  Google Scholar 

  11. Lazzeri ML, Hurle R, Casale P et al (2016) Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence. Ther Adv Urol 8:91–99

    Article  CAS  Google Scholar 

  12. Wyndaele JJJ, Riedl C, Taneja R, Lovász S, Ueda T, Cervigni M (2019) GAG replenishment therapy for bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 38(2):535–544

    Article  Google Scholar 

  13. Morales A, Emerson L, Nickel JC (1997) Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. Urology 49:111–113

    Article  CAS  Google Scholar 

  14. Shao Y, Shen ZJ, Rui WB, Zhou WL (2010) Intravesical instillation of hyaluronic acid prolonged the effect of bladder hydrodistention in patients with severe interstitial cystitis. Urology 75:547–550

    Article  Google Scholar 

  15. Ahmad I, Sarath Krishna N, Meddings RN (2008) Sequential hydrodistension and intravesical instillation of hyaluronic acid under general anaesthesia for treatment of refractory interstitial cystitis: a pilot study. Int Urogynecol J Pelvic Floor Dysfunct 19(4):543–546

    Article  Google Scholar 

  16. Sommariva ML, Sandri SD, Ceriani V (2010) Efficacy of sodium hyaluronate in the management of chemical and radiation cystitis. Minerva Urol Nefrol 62(2):145–150

    CAS  PubMed  Google Scholar 

  17. Miodosky M, Abdul-Hai A, Tsirigotis P et al (2006) Treatment of post-hematopoietic stem cell transplantation hemorrhagic cystitis with intravesicular sodium hyaluronate. Bone Marrow Transplant 38(7):507–511

    Article  CAS  Google Scholar 

  18. Constantinides C, Manousakas T, Nikolopoulos P, Stanitsas A, Haritopoulos K, Giannopoulos A (2004) Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study. BJU Int 93(9):1262–1266

    Article  CAS  Google Scholar 

  19. Cardinal J, Slade A, McFarland M et al (2018) Scoping review and meta-analysis of hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis. Curr Urol Rep 19:38

    Article  Google Scholar 

  20. Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M (2012) Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis. Eur Urol 62(5):816–830

    Article  CAS  Google Scholar 

  21. Redorta JP, Sanguedolce F, Pardo GS et al (2021) Multicentre international study for the prevention with iAluRil of radio-induced cystitis (MISTIC): a randomised controlled study. Eur Urol Open Sci 23(26):45–54

    Article  Google Scholar 

  22. Westerman ME, Boorjian SA, Linder BJ (2016) Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation. Int Braz J Urol 42:1144–1149

    Article  Google Scholar 

  23. Phelps KR, Naylor K, Brien TP et al (1999) Encephalopathy after bladder irrigation with alum: case report and literature review. Am J Med Sci 318:181–185

    Article  CAS  Google Scholar 

  24. Shah BC, Albert DJ (1973) Intravesical instillation of formalin for the management of intractable hematuria. J Urol 110:519–520

    Article  CAS  Google Scholar 

  25. Lojanapiwat B, Sripralakrit S, Soonthornphan S (2002) Intravesicle formalin instillation with a modified technique for controlling haemorrhage secondary to radiation cystitis. Asian J Surg 25:232–235

    Article  CAS  Google Scholar 

  26. Dewan AK, Mohan GM, Ravi R (1993) Intravesical formalin for hemorrhagic cystitis following irradiation of cancer of the cervix. Int J Gynaecol Obstet 42:131–135

    Article  CAS  Google Scholar 

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Funding

The study was funded by LIDDE Therapeutics SAS.

Author information

Authors and Affiliations

  1. Department of Urology and Kidney Transplantation, La Conception Hospital, Aix-Marseille University, APHM, Marseille, France

    Michael Baboudjian & Bastien Gondran-Tellier

  2. Department of Urology, CH Aix-Pertuis, Aix-en-Provence, France

    Marc Fourmarier

  3. Department of Urology, Clinique Rhône Durance, Avignon, France

    Christophe Clement

  4. Department of Urology, Clinique du Val d’Ouest, Ecully, France

    Arnaud Cherasse

  5. Department of Urology, Clinique Mutualiste de la Porte de L’Orient, Lorient, France

    Jean-Pierre Graziana

  6. Department of Urology, CH Jean Rougier, Cahors, France

    Youssef Bentaleb

  7. Department of Urology, Clinique Saint George, Nice, France

    Yohann Rouscoff

  8. Department of Urology, CH Notre Dame de la Miséricorde, Ajaccio, France

    Sylvain Ducrocq

  9. Department of Urology, NHC, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Christian Saussine

Authors
  1. Michael Baboudjian
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  2. Marc Fourmarier
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  3. Christophe Clement
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  4. Arnaud Cherasse
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  5. Jean-Pierre Graziana
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  6. Youssef Bentaleb
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  7. Yohann Rouscoff
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  8. Sylvain Ducrocq
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  9. Bastien Gondran-Tellier
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  10. Christian Saussine
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Contributions

Study concept and design: MF. Acquisition of data: MF, CC, AC, J-PG, YB, YR, SD, CS. Analysis and interpretation of data: MB, BG-T, and MF. Drafting of the manuscript: MB, MF, and CS. Critical revision of the manuscript for important intellectual content: MF and CS. Statistical analysis: BG-T.

Corresponding author

Correspondence to Michael Baboudjian.

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Conflict of interest

The authors report no conflict of interest.

Ethics approval

The study protocol and amendments were approved by the Committee for the Protection of Persons: CPP Sud-Est VI—Clermont Ferrand.

Consent to participate

Patient’s written information and participation agreement was obtained and signed from all patients.

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All authors approve the submission.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

We would like to pay tribute to the memory of Mr. Francois Schutz, chairman of LIDDE Therapeutics.

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Baboudjian, M., Fourmarier, M., Clement, C. et al. Intravesical instillation of high molecular weight sodium hyaluronate in radiation-induced cystitis: a prospective pilot study. World J Urol 40, 141–146 (2022). https://doi.org/10.1007/s00345-021-03837-9

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  • DOI: https://doi.org/10.1007/s00345-021-03837-9

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