Cryothermic and hyperthermic treatments of human leiomyomata and adjacent myometrium and their implications for laparoscopic surgery.
OBJECTIVE
To evaluate the effects and feasibility of direct cryothermic and hyperthermic therapy on leiomyomata and adjacent myometrium, and to contribute to evidence-based treatment thresholds based on measurements of direct cell injury.


METHODS
Experimental study (Canadian Task Force classification II-2).


METHODS
University hospital.


METHODS
Leiomyoma and myometrium tissue from 10 women undergoing total abdominal hysterectomy with or without bilateral salpingo-oophorectomy.


METHODS
In vitro cryothermic or hyperthermic therapy was performed with representative leiomyoma and myometrium tissue samples. Using a directional solidification stage to simulate cryothermic therapy, 10 leiomyoma and 6 myometrium specimens were cooled in vitro at a rate of -5 degrees C/minute to end temperatures of -20 degrees, -40 degrees, -60 degrees, and -80 degrees C with a 15-minute hold period and then rapidly thawed to 21 degrees C. Hyperthermic therapy was simulated using a preheated 45 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, and 80 degrees C constant temperature copper heating block with a 10-minute treatment period. In conjunction with tissue culturing and control tissues, cell death was assessed with routine histology and viability dyes (ethidium homodimer/Hoechst).


RESULTS
In cryothermic results, leiomyomata cell death (LCD) increased from 12% to 27% by histology and 26% to 38% by viability dye assay over the thermal range from -20 degrees to -80 degrees C, respectively. Myometrial cell death (MCD) increased from 10% to 12% and 4% to 20% for the same measurements, respectively. Whereas MCD appeared relatively stable from -40 degrees to -80 degrees C, it was significantly less than LCD over this range (p <0.05). For hyperthermic results, LCD increased from 17% to 88% by histology with progressive temperature increase from 45 degrees to 80 degrees C, respectively. The MCD showed a similar increase from 16% to 91% by histology over this temperature range. Hyperthermic histology and dye assay results were similar for LCD and MCD.


CONCLUSIONS
In comparison with myometrium, leiomyomata showed greater direct cryothermic and equal hyperthermic cell injury. Whereas cell death increased up to 70 degrees C and down to -80 degrees C, the interval increases in cell injury diminished with more extreme temperatures. In vivo studies of combined direct and ischemic vascular injury thresholds have yet to be performed, but direct LCD matrixes determined in this study will help provide guidelines for minimally invasive surgical techniques for the treatment of leiomyomata.
Rupp
Christopher C
CC
Department of Pathology, Robert C. Byrd Health Science Center of West Virginia University, P.O. Box 9203, Morgantown, WV 26506-2903, USA.
Nagel
Theodore C
TC
Swanlund
David J
DJ
Bischof
John C
JC
Coad
James E
JE
D000328:Adult; D000368:Aged; D002470:Cell Survival; D017679:Cryotherapy / Q000009:adverse effects* / Q000379:methods; D046508:Culture Techniques; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects* / Q000379:methods; D007044:Hysterectomy / Q000379:methods; D007150:Immunohistochemistry; D010535:Laparoscopy / Q000009:adverse effects* / Q000379:methods; D007889:Leiomyoma / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology* / Q000601:surgery; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D014594:Uterine Neoplasms / Q000473:pathology* / Q000601:surgery