cf8ea253ea6411c2432fdcad6386b067 306323.pdf c5a42c5dab102913e482d62d66b2bd5bf874e739 306323.pdf 723a4783fbb8594a840d2d47559cf88085453721c41d9bd7cf21a5a85c54dd96 306323.pdf Title: Treating BCG-Induced Cystitis with Combined Chondroitin and Hyaluronic Acid Instillations in Bladder Cancer Subject: In non-muscle invasive bladder cancer, Bacillus Calmette–Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations. 40pt Keywords: BCG; bladder cancer; cystitis; hyaluronic acid; chondroitin; intravesical instillations Author: Renate Pichler, Johannes Stäblein, Andrea Mari, Luca Afferi, David D’Andrea, Gautier Marcq, Francesco del Giudice, Francesco Soria, Jorge Caño-Velasco, José Daniel Subiela, Andrea Gallioli, Karl H. Tully, Keiichiro Mori, Achim Herms, Benjamin Pradere, Marco Moschini, Laura S. Mertens and Martin Thurnher Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Apr 3 09:52:06 2024 CEST ModDate: Wed Apr 3 09:55:59 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 7 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 6814988 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 KPNHET+VnURWPalladioL Type 1 Custom yes yes yes 16 0 OWOLSU+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 JAOSVM+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 LIPRVQ+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 51 0 RJDPUF+EURM10 Type 1 Builtin yes yes yes 68 0 FEFKCA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 80 0 FEFKCB+PalatinoLinotype CID TrueType Identity-H yes yes yes 83 0 FEFKCC+PalatinoLinotype TrueType WinAnsi yes yes no 89 0 FEFKCE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 92 0 FEFKKC+PalatinoLinotype TrueType MacRoman yes yes no 95 0 DVCMRV+CMSY10 Type 1 Builtin yes yes yes 115 0 FEFKCA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 127 0 FEFKCC+PalatinoLinotype TrueType WinAnsi yes yes no 130 0 FEFKCE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 133 0 FEFKKC+PalatinoLinotype TrueType MacRoman yes yes no 136 0 FEFKCA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 167 0 FEFKCB+PalatinoLinotype CID TrueType Identity-H yes yes yes 170 0 FEFKCC+PalatinoLinotype TrueType WinAnsi yes yes no 176 0 FEFKCE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 179 0 FEFKKC+PalatinoLinotype TrueType MacRoman yes yes no 182 0 FEHJHH+Cambria CID TrueType Identity-H yes yes yes 185 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-01-23 02:39:19 CET RepresentationInformation: 306323.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-22 14:02:35 CET Size: 6814988 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 299 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: T Helper (Th) Cells in BCG-Induced Antitumor Effects and Bladder Inflammation and Repair Destination: section.2 Item: Title: Physiological Function of the GAG Layer and the Rationale of Treating BCG-Induced Cystitis with Intravesical Instillations of GAG Components Destination: section.3 Item: Title: Methods Destination: section.4 Item: Title: Results Destination: section.5 Item: Title: Limitations Destination: section.6 Item: Title: Conclusions and Future Perspectives Destination: section.7 Item: Title: References Destination: section.8 Info: Title: Treating BCG-Induced Cystitis with Combined Chondroitin and Hyaluronic Acid Instillations in Bladder Cancer Author: Renate Pichler, Johannes Stäblein, Andrea Mari, Luca Afferi, David D’Andrea, Gautier Marcq, Francesco del Giudice, Francesco Soria, Jorge Caño-Velasco, José Daniel Subiela, Andrea Gallioli, Karl H. Tully, Keiichiro Mori, Achim Herms, Benjamin Pradere, Marco Moschini, Laura S. Mertens and Martin Thurnher Subject: In non-muscle invasive bladder cancer, Bacillus Calmette Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. 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