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57th Annual Meeting Abstracts


Poster 12

Abstract Title

Exploiting Hypotonicity In The Treatment Of Peritoneal Carcinomatosis

 

Author Block

Matthew J. Furman, MD, Barur R. Rajeshkumar, PhD, Gamze Ayata, MD, Donald H. Lambert, PhD, MD, Giles F. Whalen, MD, Laura A. Lambert, MD 

University of Massachusetts MedicalCenter, Worcester, MA

 

 

Abstract Body

Background: Hypotonic chemotherapy solutions used in regional therapy are more cytotoxic than isotonic chemotherapy. However, hypotonic solutions are rarely used due to concerns over increased systemic toxicity. This study illustrates the relative cytotoxicity of hypotonic solutions as compared with clinically relevant doses of oxaliplatin and discusses the potential role of hypotonic solutions in intraperitoneal chemotherapy.

Methods: MTT and clonogenic assays were used to determine the impact of hypotonic solutions and 0.25mM oxaliplatin in 5% dextrose (Ox) on colon cancer cells (DLD) and normal epithelial cells (MCF10A). The impact of exposure of peritoneal nodules from mouse xenographs to water or Ox were compared by H&E. Comparisons among groups were analyzed using two-sided t-test. p<0.05 was significant.

Results: There was a dose-dependent increase in cytotoxicity after exposure of cell lines to decreasing concentration of dextrose (0-5%). There was a time-dependent increase in cytotoxicity after exposure of the cell lines to water or Ox. There was no difference in cell viability after 25 min exposure to either water or oxali with almost complete cell death. Cancer cells were more sensitive to hypotonic dextrose solutions than MCF10A epithelial cells. Ox and water were equally cytotoxic to peritoneal nodules.

Conclusion: Hypotonic solutions are cytotoxic and can potentially enhance the efficacy of intraperitoneal therapies. Given concerns over the increased systemic toxicity of hypotonic intraperitoneal chemoperfusion, one option would be to perfuse the peritoneal cavity with a hypotonic solution after the chemoperfusion. In vivo studies are indicated to determine the optimal way to exploit the cytotoxicity of hypotonicity.

 

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