{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T08:20:19Z","timestamp":1781943619694,"version":"3.54.5"},"reference-count":23,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Intravesical chemotherapy may cause chemical cystitis and related lower urinary tract symptoms (LUTS). The aims of this study were to evaluate the efficacy and safety of an oral preparation of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin (Ialuril\u00ae Soft Gels) to reduce the severity of LUTS in patients with a history of bladder cancer (BCa) undergoing intravesical chemotherapy. We designed a monocentric, randomized, double-blind, placebo-controlled pilot trial. Patients referred to our institute between November 2016 and March 2018 were enrolled. All subjects had non-muscle-invasive BCa and received intravesical chemotherapy with mitomycin C (MMC). Patients were randomized 1:1 in two groups (intervention vs. control). All subjects underwent oral administration (Ialuril\u00ae Soft Gels or placebo) starting one week before the first weekly instillation and ending 30 days after the last one, subsequently starting one week before each monthly instillation and ending 14 days after it. International prostate symptom score (IPSS) and 0-100 visual analogue scale (VAS) were used to assess the efficacy of the treatment. Adverse events were also described. Patients were evaluated at baseline and after 1, 4, 7, and 13 months of intravesical chemotherapy. A total of 34 patients were enrolled. The median IPSS score was significantly lower in the intervention group compared to the control group at 4 (13 vs. 17 points; p = 0.038), 7 (10 vs. 18 points; p &lt; 0.001), and 13 (10 vs. 17 points; p = 0.002) months. The median VAS score was significantly lower in the intervention group compared to the control group at 7 (22 vs. 37 points; p = 0.021) and 13 (20 vs. 35 points; p = 0.024) months. No AE specifically related to supplement or placebo was recorded. Oral formulation of HA, CS, quercetin, and curcumin could be an effective and safe supportive therapy against chemical cystitis in patients receiving intravesical chemotherapy for BCa.<\/jats:p>","DOI":"10.3390\/pathophysiology29030028","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:12:40Z","timestamp":1657757560000},"page":"365-373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Oral Preparation of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin (Ialuril\u00ae Soft Gels) for the Prevention of LUTS after Intravesical Chemotherapy"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9706-8516","authenticated-orcid":false,"given":"Celeste","family":"Manfredi","sequence":"first","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Spirito","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6340-4403","authenticated-orcid":false,"given":"Francesco Paolo","family":"Calace","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Balsamo","sequence":"additional","affiliation":[{"name":"Urology Unit, AORN Ospedali dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Terribile","sequence":"additional","affiliation":[{"name":"Urology Unit, Clinica Trusso, 80044 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Stizzo","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Romano","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Califano","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Maria","family":"Fusco","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Rosati","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Quattrone","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Sciorio","sequence":"additional","affiliation":[{"name":"Department of Urology, ASST Lecco, Ospedale Alessandro Manzoni, 23900 Lecco, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-3330","authenticated-orcid":false,"given":"Massimiliano","family":"Creta","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Longo","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"De Sio","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5282-2335","authenticated-orcid":false,"given":"Davide","family":"Arcaniolo","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"ref_1","unstructured":"IARC (2022, May 25). 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