Flow cytometric analysis of lymph node metastases in advanced ovarian cancer: clinical and biologic significance.

OBJECTIVE: This study was undertaken to evaluate the deoxyribonucleic acid content and S-phase fraction in advanced epithelial ovarian carcinomas to determine whether lymph node metastases are biologically distinct from peritoneal sites of metastases. STUDY DESIGN: Thirty-five patients with stage III or IV epithelial ovarian cancer who had undergone complete pelvic and paraaortic lymphadenectomy had representative samples from the primary ovarian tumor, peritoneal metastases, and lymph node metastases analyzed by flow cytometry for deoxyribonucleic acid nuclear content and S-phase fraction. RESULTS: Diploid cell lines are found in metastatic lymph nodes (52%) significantly more frequently than in peritoneal metastases (25%, p < 0.02) or in primary ovarian tumors (26%, p < 0.001). The ploidy category frequency distribution of peritoneal metastases mirrors that found in the primary tumor, and both are significantly different from the ploidy category frequency distribution found in metastatic lymph nodes. Heterogeneity among sites is common, being identified in 54% of patients. Peritoneal metastases are more likely to be concordant with the primary tumor (69%) than are lymph node metastases (39%, p < 0.001). Mean S-phase fraction did not differ overall by site but was significantly different between diploid and aneuploid samples by site. Diploid lymph node metastases were found to have the lowest mean S-phase fraction (7.2% +/- 3.3%), and aneuploid lymph node metastases had the highest mean S-phase fraction (22.3% +/- 10.2%). Diploidy of the primary tumor is a positive predictor of long-term survival. Tumoral heterogeneity and lymph node metastases are not related to survival in this group of patients who underwent therapeutic pelvic and aortic lymphadenectomy. CONCLUSIONS: A high proportion of tumor deposits found in metastatic lymph nodes are diploid with a low S-phase fraction. Therapeutic pelvic and aortic lymph node dissection removes disease that, on the basis of flow cytometric characteristics, may be predicted to be resistant to chemotherapy and radiation therapy.

Laparoscopic radical hysterectomy (type III) with aortic and pelvic lymphadenectomy.

OBJECTIVE: The purpose of this study was to incorporate a wide range of operative laparoscopic techniques to complete a type III radical hysterectomy with aortic and pelvic lymphadenectomy. STUDY DESIGN: A type III radical hysterectomy with bilateral aortic and pelvic lymph node dissection was separated into eight component parts: (1) right and left aortic lymphadenectomy, (2) right and left pelvic lymphadenectomy, (3) development of the paravesical and pararectal spaces, (4) ureteral dissection, (5) ligation and dissection of the uterine artery, (6) development of the vesicouterine and rectovaginal spaces, (7) resection of the parametria, and (8) resection of the upper vagina. The adequacy of the component parts was determined and documented on video. RESULTS: Complete aortic and pelvic lymphadenectomy and a type III radical hysterectomy were performed by operative laparoscopy. Argon beam coagulation and countertraction facilitated pelvic and aortic lymph node dissection, including removal of nodal tissue lateral to the iliac vessels. Ureteral dissection with resection of the cervicovesical fascia ("the tunnel") was completed with right-angle dissectors, vascular clips, and argon-beam coagulation. Resection of the cardinal and ureterosacral ligaments was successful by use of Endo-GIA stapling instruments (United States Surgical Corporation, Norwalk, Ct.). CONCLUSION: A complete pelvic and aortic lymphadenectomy and type III radical hysterectomy were performed laparoscopically. This approach could potentially decrease morbidity historically associated with radical hysterectomy and lymphadenectomy performed either abdominally or vaginally. Only prospective randomized trails will allow for the evaluation of potential benefits associated with this surgical technique.

Laparoscopic bilateral pelvic and paraaortic lymph node sampling: an evolving technique.

OBJECTIVE: Reports describing laparoscopic lymph node sampling in patients with gynecologic malignancies have yet to describe a method to sample left-sided aortic lymph nodes that has been successful in a large series of patients. We submit our experience with evolving techniques that allow for excellent visualization and resection of both left and right aortic and pelvic lymph nodes. STUDY DESIGN: Forty patients with gynecologic malignancies underwent laparoscopy for surgical staging. Thirty-five of the patients were completely staged laparoscopically with minimal blood loss. The average number of lymph nodes sampled was 27.7 (range 14 to 35). RESULTS: Five patients required laparotomy, two to control bleeding, two to remove unsuspected intraabdominal disease, and one because of equipment failure. Four patients were rehospitalized within 30 days of surgery, two with small bowel obstructions resulting from herniation of the intestine through 12 mm trocar sites and two others with deep vein thromboses. CONCLUSION: These preliminary results demonstrate an ability to complete surgical staging in patients with gynecologic malignancies by means of specific endoscopic techniques. However, there remains a need for continued evaluation of these techniques and the associated morbidities.

Selected pulmonary biochemical and hematological changes produced by prolonged hypoxia in the rat.

Rats were exposed to 12% O2 (1 atm) for 48 hr, then 10% O2 for the duration of the exposures. Significant elevations in enzymes of the glutathione peroxidase system were found in the lungs of rats killed 3.5, 7.5, and 12.5 days of exposure compared to air-breathing controls. Superoxide dismutase was also elevated after hypoxia but nonsignificantly. Animals killed 12.5 days after exposures exhibited 75% (P less than 0.05) more thiobarbituric acid reactive products in their lungs compared to controls. These results along with significant increases of lung lipid peroxidation and in an augmentation of protective antiperoxidative lung defense capabilities. Hypoxia also resulted in enzyme elevations of lung phosphofructokinase and pyruvate kinase, which may indicate an adaptive increase in lung glycolytic capabilities which would be helpful in maintaining lung tissue energy requirements during hypoxia. In addition, it was confirmed that red blood cell count, hemoglobin and hematocrit values increased after prolonged hypoxia. The results of this study might also reflect enzyme elevation/induction due to cellular reparative-proliferative processes following hypoxia.

Oxygen toxicity: augmentation of antioxidant defense mechanisms in rat lung.

In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung "antioxidant" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.