Surgical operations have been shown to cause a variety of immunological disturbances in man both in vivo and in vitro. With few exceptions the overall picture is one of a generalized state of immunodepression in the postoperative period. The implications of these observations are that host defences may be compromised by surgical procedures, thus providing a 'fertile soil' for bacterial invasion and tumour cell metastasis at the very time when risks from invading pathogens and viable tumour cells are maximal. We have studied the effects of surgical operations on the immune system in 35 patients with benign disease. Surgical procedures were classified as either minor (n = 15) or major (n = 20). A panel of monoclonal antibodies was used to identify peripheral blood lymphocyte subpopulations and analysis was performed using flow cytometry. Simultaneous estimations of plasma alpha-1 proteinase inhibitor (alpha-1-PI), alpha-2-macroglobulin (alpha-2-M), alpha-2-pregnancy-associated glycoprotein (alpha-2-PAG) and plasma suppressive activity (PSA) on stimulated allogeneic lymphocytes were performed before operation and on postoperative days 1, 3, 7, 17 and 21. Circulating numbers of all lymphocyte subpopulations fell significantly following surgery, except for B lymphocytes which did not change. The magnitude, and duration of the reduction in cell numbers and the subpopulation affected was significantly related to the degree of surgical trauma, and returned to pre-operative values by postoperative day 7. Changes in alpha-1-PI, alpha-2-M, alpha-2-PAG and PSA were also significantly related to the degree of surgical trauma, and these plasma changes persisted longer than the cellular disturbances. Surgical operations induce a reversible depression of cellular immunity which precedes plasma suppressive activity in its return to pre-operative levels. Immunostimulating agents such as interferon and the interleukins deserve evaluation as prophylactic agents pre-operatively.
The nm23 gene was identified in murine melanoma cells, in which its expression is associated with the cells' metastatic potential. Expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry. We measured nm23 mRNA in 71 patients with primary breast cancer and found variable levels of nm23 expression. The nm23 gene was expressed at higher levels in well-differentiated tumors (P less than .02). There was a significant inverse relationship between nm23 expression and nodal status (P less than .02). Expression of nm23 was positively associated with longer disease-free survival and overall survival, and the relationships were significant (P less than .002 and P less than .003, respectively). This study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype.
It is suggested that routine level 6 prophylactic dissections should be risk-stratified. Larger tumours (T3, T4), patients aged 45 years and older or 15 years and younger, male patients, patients with bilateral or multifocal tumours, and patients with known involved lateral lymph nodes could all be candidates for routine unilateral level 6 dissection. The operation should be limited to surgeons who have the available expertise and experience.
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