ABSTRACT
Cryosurgery relies on rapid freezing, slow thawing, and repetition of the freeze-thaw cycle. As the temperature drops, extracellular water crystallizes and forms a hyperosmotic extracellular environment that draws water out of the cell. Extracellular ice crystals grow and compress the dehydrating cell membranes, resulting in severe damage. This effect of cell dehydration and solution concentration is called solutioneffect injury. Up to this point, the damage is reversible. The process is irreversible when there is intracellular ice formation; this is usually associated with rapid freezing (several degrees centigrade per minute). Pure water begins to freeze at 0C, and extracellular ice forms at approximately 8C; by 15C, intracellular ice begins to form, and, by 50C, all metabolic processes cease. Faster freezing rates and lower end temperatures have the most deleterious effects on tissue. The cooling rate should be as fast as possible, but the thawing rate, and the coldest tissue temperature reached are the principal destructive factors, and thawing should be as slow as possible. Repetition of the freeze-thaw cycle is important for effective therapy.7 Cryosurgery kills cells and destroys tissue by mechanisms that feature direct cell injury from ice crystal formation and related deleterious effects and vascular stasis caused by microcirculatory failure.8 Recently a third mechanism of cell death associated with cryosurgery has been identified. This mechanism, apoptosis or gene-regulated cell death, is additive with the direct ice-related cell damage that occurs during the operative freeze-thaw intervals and coagulative necrosis that occurs in the following days post-treatment.9,10
FINDINGS: HISTOPATHOLOGIC
Histopathologic results are considered by most to be the best absolute method for determining the extent of ablation within the prostate. Cryosurgical ablation results in
substantial tissue destruction of benign and malignant cells and there appear to be little or no differential effects on epithelium or stroma; virtually all tissue contained within the ablative zone is destroyed. Following cryosurgery, the thin rim of viable surviving tissue of the prostate shows typical features of repair, including marked stromal fibrosis and hyalinization, basal cell hyperplasia with ductal and acinar regeneration, squamous metaplasia, urothelial metaplasia, stromal hemorrhage (Figure 3.1) and hemosiderin deposition (Figure 3.2).11-15 Coagulative necrosis with devitalization is observed up to 30 weeks after therapy (Figure 3.3), but patchy chronic inflammation is more common in the late stages (Figure 3.4). The radius of necrosis was 6.0mm around a single cryoprobe after a double freeze. An array of cryprobes must be placed in the prostate to create adequate temperatures to ablate large areas of tissue. It is crucial to measure temperatures by thermocouple at the periphery and within the
prostate to ensure adequate ablation. Tissue damage extends about 1.5mm beyond the edge of the necrosis, and is characterized by squamous metaplasia and hemorrhage, as reported in patients who underwent initial cryosurgery followed by radical retropubic prostatectomy 2-3 weeks later.16 Focal granulomatous inflammation may also occur with epithelial disruption due to corpora amylacea. Dystrophic calcification is infrequent, and usually appears in areas with the greatest reparative response.
