Sterile Water Versus Glycine in Transurethral Resection of Bladder Tumors—Immunogenic and Clinical Implications

Haim Herzberg*, Roi Babaoof, Ron Marom, Yotam Veredgorn, Ziv Savin, Karin Lifshitz, Shmulik Noefeld, Rinat Lasmanovitz, Shayel Bercovich, Tomer Lamhoot, Sharon Amir, Avi Beri, David Margel, Jack Baniel, Roy Mano, Ofer Yossepowitch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background and objective: We compared the oncologic outcomes of patients with non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TUBRT) using sterile water vs glycine irrigation. The tumoricidal and immunogenic effects of these solutions on urothelial cancer cell lines were investigated. Methods: The medical records of 530 consecutive patients who underwent TURBT using sterile water or glycine irrigation for NMIBC were reviewed. Recurrence and progression rates were evaluated using time dependent analyses.Bladder cancer cell lines (RT4, T24 and 5637) were treated with glycine and sterile water. Cell viability was evaluated with the XTT assay. Cell membrane calreticulin levels were evaluated with flow cytometry. Extracellular high mobility group box 1 (HMGB1) and heat shock 70 (HSP70) protein levels were evaluated using western blots. Key findings and limitations: After propensity score matching each study arm comprised 161 patients. Median follow-up was 13.6 months (IQR 6.2, 24.5). The 2-year recurrence free survival was significantly lower in the sterile water vs glycine group (43% vs 71%, respectively, p<0.0001). Similarly, the 2-years progression free survival was significantly lower in the sterile water vs glycine group (85% vs 94%, respectively, p<0.014). Sterile water treatment resulted in the lowest number of viable cells. Early and late immunogenic cell death markers were markedly elevated in cells treated with glycine. Conclusions and clinical implications: Sterile water compared to glycine irrigation during TURBT for NMIBC was associated with higher recurrence and progression rates. Possible explanation for these findings is the diminished immune response associated with sterile water reflected in a comparatively lesser expression of immune response inducers. Patient summary: We compared two irrigation fluids in non–muscle-invasive bladder cancer surgery: glycine and sterile water. Glycine outperformed sterile water in cancer recurrence, possibly boosting immunogenicity over sterile water.

Original languageEnglish
Pages (from-to)796-804
Number of pages9
JournalEuropean Urology Focus
Volume10
Issue number5
DOIs
StatePublished - Sep 2024
Externally publishedYes

Keywords

  • Immunogenic cell death
  • Non–muscle-invasive bladder cancer
  • Recurrence
  • Transurethral resection of bladder tumor

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