Elicitation of macroscopic metastases via surgery: various forms of surgical intervention differ in their induction of metastatic outgrowth.

Surgical removal of a primary tumor implant established in a hind limb frequently gives rise to the emergence of macroscopic lymph node metastases. The present work, utilizing various kinds of surgical intervention, sets out to assess the extent to which surgery itself and/or the associated trauma were responsible for the enhancement of secondary tumor growth. The findings show that a hind limb control amputation did not affect the frequency, size or location of metastases. In contrast, comparable amputation of the tumor-bearing limb resulted in a marked increase in the incidence of macroscopic metastases. These and other findings make it likely that the more frequent and enhanced outgrowth of metastases occurring upon removal of the primary tumor implant is not the result of the operative procedure as such. Additional findings, showing that in animals bearing primary tumor implants on the limb, partial hepatectomy resulted in an enhanced outgrowth of macroscopic metastases developing in diverse locations, are more difficult to interpret. Possibly the often enhanced growth of the primary tumor implant may well favor the spread and the establishment of neoplastic cells at secondary sites; alternatively, putative growth-promoting agents, released by the regenerating liver, may stimulate primary and secondary tumor growth. The present findings diminish the likelihood that nonspecific operative stress is a major contributory factor in the enhancement of metastatic tumor growth following certain types of surgical intervention; they indicate, however, that in certain special situations of the host, such as after hepatectomy, both primary and secondary tumor growth may be enhanced.