Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors.

OBJECTIVE: Peripheral blood mononuclear cell (PBMC) dysfunction occurs following major abdominal surgery and correlates with an increased rate of septic complications. Studies have shown that dehydroepiandrosterone (DHEA) restores cell-mediated immune responses after trauma-hemorrhage in mice. Nonetheless, it remains unknown whether DHEA has any salutary effects on depressed PBMC function in surgical patients. DESIGN: Laboratory experiment. SETTING: University laboratory. PATIENTS: Fifteen patients undergoing major abdominal surgery. INTERVENTIONS: Blood samples were obtained preoperatively and 2 hrs postoperatively. MEASUREMENTS AND MAIN RESULTS: PBMCs were cultured with 33% plasma in the presence or absence of DHEA (10(-10) M, 10(-8) M physiologic concentration, 10(-6) M, 10(-5) M). In an additional set of samples, the estrogen receptor antagonist tamoxifen (10(-6) M) was added. The release of proinflammatory cytokines (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) was measured in the supernatants by enzyme-linked immunosorbent assay. Abdominal surgery resulted in depressed interleukin-1beta and tumor necrosis factor-alpha release by PBMC. Addition of DHEA to the culture medium, however, significantly improved the release of interleukin-1beta and tumor necrosis factor-alpha and stimulated the interleukin-6 release capacity of PBMC. This effect was most pronounced for a concentration of 10(-5)M DHEA. The immunomodulatory effect of DHEA on PBMC cytokine release was completely blocked by tamoxifen. In contrast, the modulatory effect of DHEA was enhanced by the addition of postoperative plasma. CONCLUSIONS: DHEA stimulates proinflammatory cytokine release capacities of human PBMCs following major abdominal surgery. The estrogen receptor appears to be involved in mediating the immunomodulatory effect of DHEA. Thus, DHEA might be a useful adjunct for preventing immunosuppression in surgical patients.

Effect of preoperative radiochemotherapy on lymph node retrieval after resection of rectal cancer.

HYPOTHESIS: Preoperative radiochemotherapy for advanced rectal cancer results in fewer lymph nodes detected in the tumor-bearing specimen. DESIGN: Nonrandomized control trial with analysis of a prospective perioperative database. SETTING: Department of Surgery of a large-volume university hospital. PATIENTS: All patients who underwent conventional open surgery to cure rectal cancer between January 1, 1996, and March 31, 2001. INTERVENTIONS: During the study period 184 patients (81%, control group) underwent surgery without receiving preoperative radiochemotherapy. Forty-two patients (19%, study group) who had advanced rectal cancer (modified Dukes stages B [tumors that have penetrated the muscle layer of the bowel wall or have gone through the bowel] or C [tumors that have spread to the lymph nodes in the same region]) received preoperative radiochemotherapy (2 cycles of fluorouracil, 4500 rad) during this period. Most patients underwent anterior rectal resection in both groups (77.7% of those who did not receive preoperative radiochemotherapy and 71.8% of those who did), the remaining patients were treated with abdominoperineal resection. RESULTS: A mean (SEM) of 19 (1) lymph nodes per specimen were detected in the control patients, while significantly fewer lymph nodes were detected in study patients (13 [1]; P<.05). The rate of inadequate lymph node staging (pNx) increased from 7% in the control group to 12% in the study group (P =.06). Pathological lymph node staging disclosed that significantly more study patients who received preoperative radiochemotherapy had modified Dukes stage A (tumors that are found only in the inner wall or rectum) cancer when compared with the control group (17% vs 0%, respectively; P<.05). CONCLUSIONS: Preoperative radiochemotherapy for advanced rectal cancer results in a significant decrease of lymph nodes detected within the tumor-bearing specimen. Preoperative radiochemotherapy induces significant downstaging with fewer positive lymph nodes and more patients presenting with Dukes stage A rectal cancer. Great care must be taken to remove an adequate number of lymph nodes and more sophisticated pathological techniques of lymph node detection are required since the tumors of ever-increasing numbers of patients are inadequately classified.