Usefulness of metyrapone treatment to suppress cancer metastasis facilitated by surgical stress.
BACKGROUND
One causative factor of tumor metastasis enhanced by surgical stress is thought to be hypersecretion of endogenous glucocorticoids. This study evaluated the effectiveness of metyrapone treatment and adrenalectomy in preventing the harmful effects of glucocorticoids in the enhancement of tumor metastasis resulting from surgical stress.


METHODS
The effect of dexamethasone on pulmonary metastasis of MRMT-1 cells and on the number of peripheral lymphocytes was evaluated in rats. To evaluate the suppressive effect of adrenalectomy and metyrapone treatment on operation-induced enhancement of metastasis, several parameters such as induction of pulmonary metastasis, serum corticosterone levels, and the number of blood lymphocytes and apoptotic thymocytes were determined.


RESULTS
With dexamethasone treatment, the number of peripheral lymphocytes rapidly decreased; in contrast, pulmonary metastasis increased. The serum corticosterone level was doubled at 1 hour, apoptotic thymocyte numbers were increased about sevenfold at 3 hours and about fourfold at 6 hours, and blood lymphocyte numbers were decreased at 3 hours after laparotomy, which facilitated about a 10-fold increase in the pulmonary metastasis. These changes were almost completely suppressed by preoperative adrenalectomy and metyrapone treatment.


CONCLUSIONS
Preoperative metyrapone treatment, which suppresses hypersecretion of endogenous glucocorticoids as a result of operation, modulates the enhancement of cancer metastases and may be an effective treatment.
Deguchi
M
M
Department of Surgery I, Fukui Medical University, Japan.
Isobe
Y
Y
Matsukawa
S
S
Yamaguchi
A
A
Nakagawara
G
G
D000315:Adrenalectomy; D000818:Animals; D017209:Apoptosis; D003345:Corticosterone / Q000097:blood; D005260:Female; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D018655:Lymphocyte Count; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008797:Metyrapone / Q000627:therapeutic use*; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013950:Thymus Gland / Q000473:pathology
D003345:Corticosterone; D008797:Metyrapone