Interstitial laser hyperthermia for colorectal liver metastases: the effect of thermal sensitization and the use of a cylindrical diffuser tip on tumor necrosis.
OBJECTIVE
Our aim in this study was to investigate the characteristics of a diffuser-tipped optical fiber in producing tumor necrosis, compared to a standard bare-tipped fiber. The potential synergistic effect between thermal sensitization by metronidazole and interstitial laser hyperthermia (ILH)-induced tumor necrosis is also evaluated.


BACKGROUND
ILH is a minimally invasive technique for the treatment of colorectal liver metastases. One of the major limitations is the size of tissue necrosis achieved by a single optical fiber. Use of cylindrical diffuser-tipped fibers and thermal sensitization of tumor cells by metronidazole may increase the size of tumor necrosis achieved by a single optical fiber.


METHODS
A model of colorectal cancer liver metastases in male inbred CBA mice was used. Laser hyperthermia was applied to tumor tissue using either a bare optical quartz fiber or a cylindrical diffuser-tipped fiber from a Medilas fibertom 4100 Nd:YAG surgical laser generator. Six hundred joules of energy was applied at two power settings, 5 and 10 watts, using bare- and diffuser-tipped fibers, respectively. The extent of necrosis was assessed by histological techniques. A similar study with three experimental groups was treated with 300 J of applied energy. Extent of immediate tumor necrosis was compared to that seen 24 h after ILH treatment. The third group, which had been treated with intraperitoneal metronidazole prior to ILH, was also assessed for tumor necrosis after 24 h and results compared with both the previous groups.


RESULTS
ILH delivered using a cylindrical diffuser-tipped fiber resulted in a significantly larger diameter of tumor necrosis when compared to a bare-tipped fiber, for a given amount of applied energy. The differences were more significant at higher power settings. Six hundred joules of energy applied by ILH using a bare-tipped fiber at 5 and 10 watts produced 6.7 +/- 1.1 mm and 5.9 +/- 0.6 mm diameter of tumor necrosis, respectively. At equivalent settings, the diffuser-tipped fiber produced 7.7 +/- 1.0 mm and 8.1 +/- 0.6 mm diameter of tumor necrosis (p = 0.02 and p < 0.001). Using a diffuser-tipped fiber and an applied energy of 300 J delivered at 5 watts power, mean diameter of tumor necrosis immediately after treatment was 6.7 +/- 1.1 mm and after 24 h 7.9 +/- 1.3 mm (p = 0.006). Mean diameter of tumor necrosis 24 h after ILH in animals treated with metronidazole was 8.3 +/- 1.9 mm (p = 0.11).


CONCLUSIONS
Diffuser-tipped optical fiber appears to significantly increase the diameter of ILH-induced tumor necrosis compared to the bare fiber. In contrast to the bare fiber, it enables the application of laser energy using higher power settings without compromising the diameter of tumor necrosis achieved. In animals treated with metronidazole, a trend towards increased tumor destruction at the tumor-host interface was seen on histolopathology. In addition, a trend towards increased diameter of tumor necrosis was also seen; however, statistical significance was not achieved.
Department of Surgery, Monash University, Alfred Hospital, Prahran, Australia. Vijayaragavan.Muralidharan@med.monash.edu.au
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Muralidharan
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Malcontenti-Wilson
Chris
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Christophi
D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D006979:Hyperthermia, Induced / Q000379:methods*; D053685:Laser Therapy; D008114:Liver Neoplasms, Experimental / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D009336:Necrosis
D008795:Metronidazole