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Technology Reviews

Adjuvant Approaches to Enhance Cryosurgery

[+] Author and Article Information
Raghav Goel

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455

Kyle Anderson, Joel Slaton

Medical School Department of Urologic Surgery, University of Minnesota, Minneapolis, MN 55455

Franz Schmidlin

 Clinic des Grangettes, Chemin des Grangettes 7, Chêne-Bougeries, Geneva 1224, Switzerland

Greg Vercellotti, John Belcher

Department of Medicine, University of Minnesota, Minneapolis, MN 55455

John C. Bischof1

Department of Biomedical Engineering, Department of Mechanical Engineering, and Medical School Department of Urologic Surgery, University of Minnesota, Minneapolis, MN 55455bischof@umn.edu

1

Corresponding author.

J Biomech Eng 131(7), 074003 (Jul 28, 2009) (11 pages) doi:10.1115/1.3156804 History: Received January 08, 2009; Revised May 14, 2009; Published July 28, 2009

Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue.  This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions.  Two important motivations for adjuvant use are:  (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site).  This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo.  The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including:  thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators.  The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.

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Copyright © 2009 by American Association of Physics Teachers
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Figures

Grahic Jump Location
Figure 1

Outcome of a cryosurgical procedure. Complete tissue destruction is usually obtained at temperatures less than −40°C. Direct cell injury, vascular injury, and immune injury mechanisms compete in defining the edge of destruction above −40°C.

Grahic Jump Location
Figure 2

Mechanisms of cryosurgical injury. Tissue destruction is achieved by (a) direct cell injury, (b) vascular injury, and (c) immunological injury (modified from Ref. 1).

Grahic Jump Location
Figure 3

Improvements in a cryosurgical procedure by the use of adjuvants

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