The effect of starvation on blood stream cancer cell metastasis to the liver in rat after laparotomy.
BACKGROUND
Preoperative malnutrition worsens the prognosis of cancer patients. However, it is not certain how preoperative malnutrition affects postoperative hematogenous metastasis. We examined the influence of preoperative starvation on liver metastasis in rats using intra-vascular injection of AH109A hepatoma cells.


METHODS
Male donryu rats were divided into Fasting and Control groups. Rats received laparotomy and (125)I-iodo-deoxyuridine labeled AH109A hepatoma cells were inoculated via superior mesenteric vein. Radioactivity in the organs, macroscopic liver metastasis, white blood cell count, leukocyte count, NK cell activity, endogenous serum corticosterone and ACTH concentration and mRNA expression of cytokine in the liver and brain were evaluated at certain time points.


RESULTS
48hours preoperative starvation reduced body weight and induced a state of malnutrition. Accumulation of radioactivity in the liver was more than 4 times higher, and the number of liver metastases was 3.5 times higher in the Fasting than in the Control group. Preoperative starvation caused an almost 2 fold increase in plasma endogenous corticosterone levels and a 66% reduction in white blood cell and lymphocyte counts. Postoperative hypothalamus pituitary adrenal axis response was preserved. In addition, inflammatory cytokine expression in the liver was suppressed in the starved animals, suggesting that preoperative starvation led to a state of cellular immunosuppression, which would be an important factor for liver metastasis.


CONCLUSIONS
Preoperative malnutrition by 48 hours starvation reduced inflammatory cytokine response and cellular immunity, resulting in an increase in hematogenous liver metastasis.
Department of Surgery, Kurume University School of Medicine.
Tatsuya
T
Muraoka
Kazuo
K
Shirouzu
Hiroyuki
H
Ozasa
Yousuke
Y
Oka
Kazuya
K
Momosaki
Nobutaka
N
Iwakuma
Katsuaki
K
Tanaka
Nobuya
N
Ishibashi
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D015850:Interleukin-6 / Q000097:blood; D007694:Killer Cells, Natural / Q000166:cytology; D007813:Laparotomy / Q000379:methods*; D007958:Leukocyte Count; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D044342:Malnutrition; D009362:Neoplasm Metastasis; D010913:Pituitary-Adrenal System; D051381:Rats; D013217:Starvation; D013997:Time Factors
D016207:Cytokines; D015850:Interleukin-6; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone