Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats

Shahar Bar-Yosef, Rivka Melamed, Gayle G. Page, Guy Shakhar, Keren Shakhar, Shamgar Ben-Eliyahu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

250 Scopus citations


Background: The perioperative period is characterized by a state of immunosuppression, which was shown in animal studies to underlie the promotion of tumor metastasis by surgery. As this immunosuppression is partly ascribed to the neuroendocrine stress response, the authors hypothesized that spinal blockade, known to attenuate this response, may reduce the tumor-promoting effect of surgery. Methods: Fischer-344 rats were subjected to a laparotomy during general halothane anesthesia alone or combined with either systemic morphine (10 mg/kg) or spinal block using bupivacaine (50 μg) with morphine (10 μg). Control groups were either anesthetized or undisturbed. Blood was drawn 5 h after surgery to assess number and activity of natural killer cells, or rats were inoculated intravenously with MADB106 adenocarcinoma cells, which metastasize only to the lungs. Metastatic development was assessed by quantifying lung retention of tumor cells 24 h after inoculation or by counting pulmonary metastases 3 weeks later. Results: Laparotomy conducted during general anesthesia alone increased lung tumor retention up to 17-fold. The addition of spinal block reduced this effect by 70%. The number of metastases increased from 16.7 ± 10.5 (mean ± SD) in the control group to 37.2 ± 24.4 after surgery and was reduced to 10.5 ± 4.7 during spinal block. Systemic morphine also reduced the effects of surgery, but to a lesser degree. Natural killer cell activity was suppressed to a similar extent by surgery and by anesthesia alone. Conclusions: The addition of spinal blockade to general halothane anesthesia markedly attenuates the promotion of metastasis by surgery.

Original languageEnglish
Pages (from-to)1066-1073
Number of pages8
Issue number6
StatePublished - 2001


FundersFunder number
National Cancer InstituteR01CA073056


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