Effect of interstitial laser hyperthermia in a murine model of colorectal liver metastases.
Interstitial laser hyperthermia (ILH) is an in situ ablative technique used for the treatment of colorectal liver metastases. At present, few data exist concerning the optimum power settings required to maximize tissue necrosis. The aim of this study was to establish the dose-response relationship between the laser power setting and the extent of tissue necrosis produced in liver and tumor tissue, as well as the pattern of necrosis in a murine model of liver metastases. An intrasplenic induction model of liver metastases in 4- to 6-week-old male inbred CBA mice was used. Laser hyperthermia was applied to liver and tumor tissue using a bare optical quartz fiber from a Laserex SLY500 Nd:YAG surgical laser generator. Two-watt and 5-watt power settings were used at specific time intervals. The livers were then excised, fixed in formalin, and the extent and degree of necrosis were measured. Results were expressed as mean +/- standard deviation and were normally distributed. Analysis of variance was performed, and the least significant difference was used for post hoc tests. A P value of less than 0.05 was considered significant. Interstitial laser hyperthermia at 5 watts of power produced larger diameters of necrosis than did 2 watts for specific exposure times in normal liver tissue. However, when the total energy applied was compared, there was no significant difference in the diameters of tissue necrosis produced by the two power settings. The diameter of tissue necrosis in the normal liver increased from 2 mm at 10 joules to 8 mm at 600 joules of energy. Within tumor tissue, ILH at 2 and 5 watts produced similar diameters of necrosis for specific exposure times. When amounts of total energy applied were compared, ILH at the lower power setting (2 watts) produced a significantly larger diameter of necrosis than the higher power setting (5 watts). The diameter of necrosis achieved in tumor tissue was significantly larger than that in normal liver tissue at both power settings, for an equivalent amount of applied energy. The difference was more pronounced when ILH was performed at the lower power setting. The maximum diameter of necrosis achieved was 6.8 +/- 0.7 mm in normal liver tissue and 7.7 +/- 0.8 mm in tumor tissue. Charring of the fiber tip was delayed when the lower power setting was used, occurring after 20 seconds of exposure, compared to 5 seconds at the higher power setting. Similarly, cavitation occurred initially at 50 seconds at 5 watts of power and was delayed until 90 seconds of exposure at 2 watts of power. Histopathologic findings revealed an elliptical area of homogeneous necrosis, with a central acellular coagulum surrounded by intact but non-viable tissue. ILH is capable of producing highly reproducible, uniform, and complete tissue necrosis. The diameter of necrosis is related to the total energy applied. At low-power settings at any given amount of applied energy, a significantly larger diameter of tissue necrosis was achieved in tumor tissue compared to normal liver tissue.
Muralidharan
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Department of Surgery, Monash University, Alfred Hospital, Prahran, Australia. Vijayaragavan.Muralidharan@med.monash.edu.au
Malcontenti-Wilson
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Christophi
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D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced / Q000379:methods; D017075:Laser Coagulation / Q000009:adverse effects / Q000379:methods*; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary* / Q000601:surgery*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015999:Multivariate Analysis; D009336:Necrosis; D011336:Probability