Progressive microvascular injury in liver and colorectal liver metastases following laser induced focal hyperthermia therapy.
OBJECTIVE
Focal hyperthermia by laser or radiofrequency is currently the preferred method for local ablation of liver tumors. The underlying mechanism of action of focal hyperthermia, in particular the relationship between the microvascular and tissue effect is uncertain and was investigated in a murine model.


METHODS
Focal hyperthermia produced by a Neodymium-Yttrium-Aluminium-Garnet laser (wavelength 1,064 nm) was applied to the normal liver and colorectal cancer liver metastases in inbred male CBA strain mice at 2 W for 50 seconds (100 J). Tissue injury was assessed at 0, 24, 48, 72, 120, and 168 hours following therapy by measurements of necrosis in tissue sections stained for nicotinamide adenine dinucleotide (NADH) diaphorase activity. Characteristics of microvascular injury were assessed at the various time points by scanning electron microscopy (SEM) of vascular resin casts, Laser Doppler flowmetry, and confocal in vivo microscopy.


RESULTS
Focal hyperthermia produced progressive tissue and vascular injury. There was an initial reduction in blood flow and increased vascular permeability in the microcirculation of both tumor and liver tissue immediately following heat application as assessed by laser Doppler flowmetry and confocal in vivo microscopy, respectively. SEM of vascular casts showed heterogeneous regions of microvascular injury immediately following heat application. The extent of initial vascular disruption or occlusion on SEM of vascular resin casts (mean+/-SE) was significantly less than the tissue necrosis in liver (1.9+/-0.1 mm vs. 3.0 mm+/-0.2 mm P<0.001), but was equivalent to the tissue injury in tumor tissue (3.5 mm+/-0.2 mm vs. 3.6 mm+/-0.1 mm P = 0.907). This was followed by a progressive increase in both microvascular and tissue injury in liver and tumor that peaked by 72 hours following treatment. The peak microvascular injury and tissue damage in liver (6.6 mm+/-0.2 and 6.3 mm+/-0.2 mm, respectively) was significantly greater than the extent of microvascular and tissue damage in tumors (4.8 mm+/-0.2 mm and 4.5 mm+/-0.2 mm, respectively) (P<0.001). The progression of microvascular injury in liver and tumor at times preceded the tissue injury.


CONCLUSIONS
Focal hyperthermia produces both progressive microvascular and tissue damage in liver and colorectal liver metastases. An increase in tissue injury following focal hyperthermia may be a direct result of progressive microvascular damage. Tumor vessels appear more susceptible to direct focal hyperthermia destruction than liver sinusoids. The liver sinusoids are however more susceptible to progressive damage or occlusion following the initial laser thermal stimulus.
Nikfarjam
Mehrdad
M
Department of Surgery, University of Melbourne, Austin Hospital, Lance Townsend Building Level 8, Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia.
Muralidharan
Vijayaragavan
V
Malcontenti-Wilson
Caterina
C
Christophi
Christopher
C
D000818:Animals; D001808:Blood Vessels / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000628:therapy*; D018450:Disease Progression; D006979:Hyperthermia, Induced / Q000379:methods; D053685:Laser Therapy / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000528:radiation effects*; D008113:Liver Neoplasms / Q000098:blood supply / Q000628:therapy*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000628:therapy; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000528:radiation effects; D023421:Models, Animal