{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:33:22Z","timestamp":1792643602541,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Surg."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Radiation cystitis (RC) is a well\u2013recognized complication of pelvic irradiation, manifesting as symptoms and signs such as hematuria, pain during urination, chronic pelvic pain, urgency and incontinence, which negatively impact patients' quality of life. We conducted a retrospective observational clinical investigation to evaluate the effect of bladder instillation with Adelmidrol (ADM) and sodium hyaluronate (HA) in patients with symptomatic RC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected data from the patients' clinical records for all patients treated in our hospital with a diagnosis of RC and undergoing a cycle of 8 weekly 60 min bladder instillations with 50 mL a solution of 2% ADM\u2009+\u20090.1% HA. We evaluated the presence of pain (measured with the VAS score), urinary urgency\/frequency, macroscopic hematuria and incontinence (all registered as a dichotomous variable present\/absent) before and at the end of the treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pelvic pain, evaluated by Visual Analogue Scale (VAS), improved in 66.7% of patients, significantly decreasing from a mean score of 3.8\u2009\u00b1\u20090.47\u20131.1\u2009\u00b1\u20090.3 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.0001). Gross hematuria and urgency, presented by 83.3% and 90.0% of patients, were reported by 6.7% and 33.3%, respectively, after the end of treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.0001). Incontinence, at first reported by 43.3% of the considered patients, disappeared in 16.7% of the subjects (n.s.).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results suggest the beneficial effect of ADM + HA intravesical instillations in managing RC symptoms, especially pain, gross hematuria and urgency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fsurg.2025.1735532","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:49:57Z","timestamp":1769528997000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of bladder instillations with adelmidrol and sodium hyaluronate for the treatment of symptomatic radiation cystitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Francesco M.","family":"Bracco","sequence":"first","affiliation":[{"name":"Urology Clinic, Department of Surgical Sciences, A.O.U. Citt\u00e0 Della Salute e Della Scienza di Torino, University of Turin","place":["Turin, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Ammirati","sequence":"additional","affiliation":[{"name":"Neuro-Urology, CTO-Spinal Cord Unit, Citt\u00e0 Della Salute e Della Scienza di Torino","place":["Turin, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giamm\u00f2","sequence":"additional","affiliation":[{"name":"Neuro-Urology, CTO-Spinal Cord Unit, Citt\u00e0 Della Salute e Della Scienza di Torino","place":["Turin, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gontero","sequence":"additional","affiliation":[{"name":"Urology Clinic, Department of Surgical Sciences, A.O.U. Citt\u00e0 Della Salute e Della Scienza di Torino, University of Turin","place":["Turin, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s11764-015-0481-8","article-title":"Effects of radiation therapy on the structure and function of the pelvic floor muscles of patients with cancer in the pelvic area: a systematic review","volume":"10","author":"Bernard","year":"2016","journal-title":"J Cancer Surviv"},{"key":"B2","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.semradonc.2017.04.010","article-title":"Pelvic radiation and normal tissue toxicity","volume":"27","author":"Nicholas","year":"2017","journal-title":"Semin Radiat Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"346812","DOI":"10.1155\/2015\/346812","article-title":"A narrative review on the pathophysiology and management for radiation cystitis","volume":"2015","author":"Browne","year":"2015","journal-title":"Adv Urol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1748-717X-9-44","article-title":"Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance","volume":"9","author":"Sveistrup","year":"2014","journal-title":"Radiat Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/cells10010021","article-title":"Chronic inflammation and radiation-induced cystitis: molecular background and therapeutic perspectives","volume":"10","author":"Helissey","year":"2020","journal-title":"Cells"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.urology.2018.07.017","article-title":"Urologic complications following pelvic radiotherapy","volume":"122","author":"Lobo","year":"2018","journal-title":"Urology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.4240\/wjgs.v7.i11.279","article-title":"Pelvic radiation therapy: between delight and disaster","volume":"7","author":"Al Morris","year":"2015","journal-title":"World J Gastrointest Surg"},{"key":"B8","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.urology.2024.04.035","article-title":"Incidence and management of radiation cystitis after pelvic radiotherapy for prostate cancer: analysis from a national database","volume":"191","author":"Bologna","year":"2024","journal-title":"Urology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nrurol.2010.23","article-title":"Management of radiation cystitis","volume":"7","author":"Smit","year":"2010","journal-title":"Nat Rev Urol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.urology.2015.11.001","article-title":"Modeling and treatment of radiation cystitis","volume":"88","author":"Zwaans","year":"2016","journal-title":"Urology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1007\/s11884-019-00538-3","article-title":"Radiation cystitis: a contemporary review","volume":"14","author":"Alazem","year":"2019","journal-title":"Curr Bladder Dysfunct Rep"},{"key":"B12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5772\/intechopen.111698","article-title":"Radiation cystitis","volume-title":"Cystitis\u2014Updates and Challenges","author":"Levi D\u2019ancona","year":"2023"},{"key":"B13","doi-asserted-by":"publisher","first-page":"152736","DOI":"10.1016\/j.cej.2024.152736","article-title":"Amelioration of radiation cystitis by tetrahedral framework nucleic acid nanostructures functionalized with quercetin","volume":"493","author":"Wang","year":"2024","journal-title":"Chem Eng J"},{"key":"B14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.bcp.2016.09.001","article-title":"Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation","volume":"119","author":"Impellizzeri","year":"2016","journal-title":"Biochem Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.phrs.2018.05.013","article-title":"Adelmidrol\u2009+\u2009sodium hyaluronate in IC\/BPS or conditions associated to chronic urothelial inflammation. A translational study","volume":"134","author":"Ostardo","year":"2018","journal-title":"Pharmacol Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.34057\/PPj.2023.42.01.2023-1-2","article-title":"Adelmidrol\u2009+\u2009hyaluronic acid in the treatment of symptoms associated with intravesical anticancer therapy in non-muscle invasive bladder cancer. An observational retrospective investigation","volume":"42","author":"Canepa","year":"2023","journal-title":"Pelviperineology"},{"key":"B17","first-page":"99","article-title":"Prevenzione con adelmidrol\u2009+\u2009acido ialuronico dei sintomi indotti da terapia oncologica endovescicale per il trattamento del carcinoma uroteliale non muscolo-invasivo: risultati a lungo termine","volume":"42","author":"Canepa","year":"2023","journal-title":"Pelviperineologia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.29011\/2575-8241.001346","article-title":"Adelmidrol protects hyaluronic acid against oxidative degradation and improves the outcome in patients with adhesive capsulitis of the shoulder managed by physical therapy. In vitro evidence and two case reports","volume":"9","author":"Cavallaro","year":"2024","journal-title":"J Orthop Res Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1021\/bm050867v","article-title":"Degradative action of reactive oxygen species on hyaluronan","volume":"7","author":"Solt\u00e9s","year":"2006","journal-title":"Biomacromolecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ctro.2022.10.009","article-title":"Investigation of the physiological response of radiation-induced cystitis patients using hyperbaric oxygen","volume":"38","author":"Gulli","year":"2023","journal-title":"Clin Transl Radiat Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"9068","DOI":"10.3390\/ijms24109068","article-title":"Revolutionizing radiotoxicity management with mesenchymal stem cells and their derivatives: a focus on radiation-induced cystitis","volume":"24","author":"Helissey","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.freeradbiomed.2016.12.036","article-title":"Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model","volume":"103","author":"Oscarsson","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0090-4295(01)01129-3","article-title":"Mast cell involvement in interstitial cystitis: a review of human and experimental evidence","volume":"57","author":"Theoharides","year":"2001","journal-title":"Urology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1600-065X.2007.00528.x","article-title":"The essential role of mast cells in orchestrating inflammation","volume":"217","author":"Kinet","year":"2007","journal-title":"Immunol Rev"},{"key":"B25","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1159\/000087569","article-title":"Role of oxidants in mast cell activation","volume":"87","author":"Suzuki","year":"2005","journal-title":"Chem Immunol Allergy"},{"key":"B26","doi-asserted-by":"publisher","first-page":"6219","DOI":"10.1038\/s41598-024-56655-5","article-title":"The effect of myeloablative radiation on urinary bladder mast cells","volume":"14","author":"Smith","year":"2024","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3312","DOI":"10.1098\/rstb.2011.0391","article-title":"Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide","volume":"367","author":"Skaper","year":"2012","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00709-010-0112-1","article-title":"Formation and maintenance of blood-urine barrier in urothelium","volume":"246","author":"Kreft","year":"2010","journal-title":"Protoplasma"},{"key":"B29","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.suc.2016.02.007","article-title":"Diagnosis and management of hematuria","volume":"96","author":"Avellino","year":"2016","journal-title":"Surg Clin N Am"},{"key":"B30","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.ajpath.2012.10.020","article-title":"MiR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome","volume":"182","author":"Monastyrskaya","year":"2013","journal-title":"Am J Pathol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1152\/ajpregu.00367.2009.-NGF","article-title":"Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function","volume":"298","author":"Schnegelsberg","year":"2010","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12894-015-0046-1","article-title":"Sodium hyaluronate and chondroitin sulfate replenishment therapy can improve nocturia in men with post-radiation cystitis: results of a prospective pilot study","volume":"15","author":"Gacci","year":"2015","journal-title":"BMC Urol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1159\/000365711","article-title":"Intravesical therapies for radiation cystitis","volume":"8","author":"Giannitsas","year":"2015","journal-title":"Curr Urol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.31925\/farmacia.2019.1.7","article-title":"The efficiency of hyaluronic acid in the management of radiation induced cystitis","volume":"67","author":"Marcu","year":"2019","journal-title":"Farmacia"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e108299","DOI":"10.5812\/ijcm.108299","article-title":"Intravesical instillation of sodium hyaluronate (cystistat\u00ae) for the treatment of patients with radiation cystitis-randomized clinical trial","volume":"13","author":"Allameh","year":"2020","journal-title":"Int J Cancer Manag"},{"key":"B36","doi-asserted-by":"publisher","first-page":"18","DOI":"10.4172\/jbb.1000174","article-title":"Use of hyaluronic acid (cystistat) for the treatment of late radiation induced cystitis in patients after prostate irradiation","volume":"6","author":"Vasssilis","year":"2014","journal-title":"J Bioequivalence Bioavailab"},{"key":"B37","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1464-410X.2011.10550.x","article-title":"Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis","volume":"109","author":"Shao","year":"2012","journal-title":"BJU Int"},{"key":"B38","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1177\/1721727X1401200117","article-title":"Intravesical hyaluronic acid and chondroitin sulphate improve symptoms and quality of life in patients with late radiation tissue cystitis: an investigative pilot study","volume":"12","author":"Sommariva","year":"2014","journal-title":"Eur J Inflamm"},{"key":"B39","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00345-021-03837-9","article-title":"Intravesical instillation of high molecular weight sodium hyaluronate in radiation-induced cystitis: a prospective pilot study","volume":"40","author":"Baboudjian","year":"2022","journal-title":"World J Urol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3390\/antiox12040824","article-title":"Hyaluronan and reactive oxygen species signaling\u2014novel cues from the matrix?","volume":"12","author":"Berdiaki","year":"2023","journal-title":"Antioxidants"},{"key":"B41","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S0022-5347(05)64750-7","article-title":"Mast cell activation triggers a urothelial inflammatory response mediated by tumor necrosis factor-\u03b1","volume":"168","author":"Batler","year":"2002","journal-title":"J Urol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.urology.2006.08.1109","article-title":"The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis","volume":"69","author":"Sant","year":"2007","journal-title":"Urology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s12031-016-0774-z","article-title":"Effects of CYP-induced cystitis on growth factors and associated receptor expression in micturition pathways in mice with chronic overexpression of NGF in urothelium","volume":"59","author":"Girard","year":"2016","journal-title":"J Mol Neurosci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.4049\/jimmunol.1300825","article-title":"Nerve growth factor downregulates inflammatory response in human monocytes through TrkA","volume":"192","author":"Prencipe","year":"2014","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s00281-018-0674-0","article-title":"Role of neurogenic inflammation in local communication in the visceral mucosa","volume":"40","author":"Birder","year":"2018","journal-title":"Semin Immunopathol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.clgc.2016.01.016","article-title":"Bladder instillation therapy with hyaluronic acid and chondroitin sulfate improves symptoms of postradiation cystitis: prospective pilot study","volume":"14","author":"Gacci","year":"2016","journal-title":"Clin Genitourin Cancer"},{"key":"B47","doi-asserted-by":"publisher","first-page":"344.e19","DOI":"10.1016\/j.urolonc.2022.02.013","article-title":"Intravesical instillation with glycosaminoglycan replacement treatment in patients suffering radiation-induced haemorrhagic cystitis: when and which patients can benefit most from it?","volume":"40","author":"Sanguedolce","year":"2022","journal-title":"Urol Oncol"}],"container-title":["Frontiers in Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2025.1735532\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:49:58Z","timestamp":1769528998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2025.1735532\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":47,"alternative-id":["10.3389\/fsurg.2025.1735532"],"URL":"https:\/\/doi.org\/10.3389\/fsurg.2025.1735532","relation":{},"ISSN":["2296-875X"],"issn-type":[{"value":"2296-875X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"article-number":"1735532"}}