Does surgical stress cause tumor metastasis?
The purpose of this study was to test the validity of our working hypothesis that the stress of radical surgery may affect the prognosis of a cancer patient by precipitating hematogenous tumor metastasis, and that enhancement of this type of tumor metastasis is mediated by an increase of glucocorticoid activity that is induced in a cancer patient by surgical stress. Practically, we looked for the presence of glucocorticosteroid excess in cervical cancer patients in the course of radical surgery, and also tested the possible impact of glucocorticoid excess on the development of tumor metastasis in mice with i.v. inoculated Ehrlich ascites clone 1 tumor cells. The results obtained indicated that: 1) a state of glucocorticoid excess was observed in cancer patients at an early stage of postoperative convalescence. 2) Development of lung metastasis of blood-borne Ehrlich ascites tumor cells was facilitated in mice by hydrocortisone pretreatment--a substitute for surgical stress conditioning. 3) In the enhancement of lung metastasis, the hormone was found to induce constriction of the lung capillary lumen on the one hand, and acceleration of microvillus growth of the tumor cell surface on the other hand two morphological changes that may facilitate intrapulmonary retention of tumor cells. 4) Cyclophosphamide, as tested in a series of adjuvant chemotherapy experiments, was effective in either retarding or arresting the progress of tumor metastasis in hydrocortisone-conditioned mice. The possible impact of surgical stress on the spread of blood-borne tumor cells to the lung and liver, as well as on the therapeutic effect of cyclophosphamide for the prevention of postoperative micrometastasis, is discussed in the light of glucocorticoid actions on its target tissues.
Kodama
M
M
Kodama Research Institute of Preventive Medicine, Laboratory of Service Section, Nagoya, Japan.
Kodama
T
T
Nishi
Y
Y
Totani
R
R
D000818:Animals; D002196:Capillaries / Q000648:ultrastructure; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006728:Hormones / Q000652:urine*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007044:Hysterectomy / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary* / Q000648:ultrastructure; D008593:Menopause; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009362:Neoplasm Metastasis / Q000473:pathology*; D013256:Steroids / Q000652:urine*; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*; D002583:Uterine Cervical Neoplasms / Q000601:surgery* / Q000652:urine
D006728:Hormones; D013256:Steroids; D003520:Cyclophosphamide; D006854:Hydrocortisone