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Invasive cervical cancer is characterized by basement membrane-invading lesions capable of metastasizing through the lymphatic and vascular systems. Treatment methods were reviewed by panelists at the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), and new opportunities for translational research were discussed. Reviews encompassed hysterectomy with or without lymph node dissection or cervical conization in cases with microinvasion and radical trachelectomy with or without lymph node dissection as fertility-sparing surgery. Chemoradiation is used to treat advanced cervical malignancies, and the risks and benefits of radiotherapy are significant. Pelvic exenteration is used to treat certain types of recurrences. Use of the Miami pouch for continent urinary diversion was highlighted. Gynecologic oncologists expect novel in vivo imaging techniques currently being developed to help guide therapy choices within the next decade. The most significant research priorities are large group-randomized trials involving fertility-sparing procedures and the management of microinvasive carcinoma (MICA); better identification of candidates for chemoradiation; and the development of innovative approaches to exenteration. Improving diagnostic technologies, refining the criteria by which therapies are chosen, and preserving fertility remain challenges in selecting the most appropriate treatment for invasive cervical cancer. Research advances in both diagnosis and treatment are expected to improve therapy and outcomes., (Copyright 2003 American Cancer Society.)

Background: Cancer cell growth is an energy-related process supported by an increased glucose metabolism. The objective of this study was to investigate the association of GLUT-1 with response to chemotherapy and outcome in patients with ovarian carcinoma., Methods: Histologic sections of formalin fixed, paraffin embedded specimens from 113 primary ovarian carcinomas were stained for GLUT-1 by using polyclonal GLUT-1 antibody (Dako Co., Carpinteria, CA) and the labeled streptavidin biotin procedure. Intensity of GLUT-1 staining was compared with disease free survival (DFS), chemotherapy response, and other clinicopathologic characteristics., Results: GLUT-1 cytoplasmic membrane staining was observed in 89 of 104 (85.6%) malignant tumors. Poorly differentiated tumors showed a trend to overexpress the GLUT-1 protein compared with the more differentiated counterparts (27.6% vs. 8.7%; P = 0.08). Patients who experienced a complete clinical response to chemotherapy were more frequently GLUT-1 positive than GLUT-1 negative (80% vs. 51.5%; P = 0.036). In multivariate analysis of advanced stage disease, residual tumor (P = 0.0001) and high GLUT-1 expression levels (P = 0.028) were the only independent variables that maintained a significant association with response to chemotherapy (P = 0.0001; chi-square = 38.13). In the subgroup of Stage III-IV (International Federation of Gynecology and Obstetrics patients showing a complete clinical response, GLUT-1 overexpression was associated with a shorter DFS. The median time to progression was 30 months in GLUT-1 strongly positive cases (> 50% of cancer cells positive) versus 60 months in GLUT-1 weakly positive cases (< or = 50% of cancer cells positive; P = 0.024)., Conclusions: GLUT-1 status is an independent prognostic factor of response to chemotherapy in advanced stage ovarian carcinoma. Moreover, patients overexpressing GLUT-1 show a significantly shorter DFS. These results suggest that the assessment of GLUT-1 status may provide clinically useful prognostic information in patients with ovarian carcinoma., (Copyright 2001 American Cancer Society.)

Background: Several studies have shown that nitric oxide (NO)-releasing agents can kill tumor cells. Unfortunately, currently available NO delivery molecules do not target tumor cells preferentially. To exploit the overexpression of glucose transport proteins and the high level of glucose transport characteristics of tumor cells, glucose was conjugated to S-nitroso-N-acetyl-penicillamine (2-gluSNAP) and evaluated for cytotoxicity in human ovarian carcinoma cells., Methods: The cytotoxicity of 2-gluSNAP and SNAP was assessed by clonogenic cell survival assays performed in A2780S (cisplatin sensitive) and A2780cP (cisplatin-resistant) ovarian carcinoma cells in vitro. Immunoblotting and immunohistochemistry were used to assess the expression of Glut-1 hexose transport protein in the cell lines as well as in paraffin blocks from 28 surgical specimens of epithelial ovarian carcinoma. Apoptosis was assessed by an end-labeling assay., Results: The ovarian carcinoma cell lines consistently were more sensitive to 2-gluSNAP than SNAP alone. The median effective doses (MEDs) for 2-gluSNAP and SNAP in the A2780s cell line were 0.0042 microM and 20.4 microM, respectively. Therefore, 2-GluSNAP was nearly 5000-fold more potent than the NO-donating moiety (SNAP) alone. In the A2780cP cells, the MED for 2-gluSNAP (0.38 microM) was 250-fold lower than that for SNAP alone (100 microM). Immunoblotting and immunohistochemistry studies showed overexpression of Glut-1 in the cell lines and in 23 of 28 epithelial ovarian carcinoma specimens., Conclusions: The novel glyco-NO conjugate 2-gluSNAP exhibits a much greater cytotoxicity than the parent NO donor without the hexose moiety. These agents have the potential to target tumor cells preferentially, that overexpress Glut-1. This transporter is expressed highly in epithelial ovarian carcinoma., (Copyright 2000 American Cancer Society.)

Background: Data analysis of the recent National Survey of Ovarian Carcinoma revealed significant differences in patterns of care among various physician specialists. The goal of this study was to determine if different care patterns led to differences in patient survival., Methods: Data were collected from 25 consecutive patients with ovarian cancer diagnosed in 1983 and 1988 from 1230 hospitals with cancer programs across the United States., Results: A total of 12,316 patients from 904 hospitals were registered, of whom 20.8% were cared for by gynecologic oncologists (GYO), 45.0% by obstetrician-gynecologists (OBG), and 21.1% by general surgeons (GS). GYO preferred the upper-lower midline incision in 44.1% of patients, whereas both OBG and GS chose the low midline approach in 44-45%. GYO performed more hysterectomies, oophorectomies, omentectomies, and lymph node and peritoneal biopsies than did other specialists. Although the rates of surgery of the small intestine were comparable between GYO and GS, the latter performed significantly more colostomies and resections of the large intestine. The optimal debulking rates were: GYO, 42-45%; OBG, 40-44%; and GS 25%. There was no significant survival difference between patients cared for by GYO and those cared for by OBG for all stage divisions. However, with the exception of patients with Stage I disease, patients cared for by GS had significantly reduced survival than did those cared for by GYO and OBG (P < 0.004)., Conclusion: Efforts must be made to ensure that more patients with ovarian cancer are cared for by physicians in the appropriate specialties.

Background: The Commission on Cancer of the American College of Surgeons recently completed a national survey of patients with ovarian cancer. From the large database, the prognostic value of current International Federation of Gynecology and Obstetrics (FIGO) staging system for ovarian carcinoma was re-examined., Methods: Data was collected from 25 consecutive ovarian carcinomas diagnosed in 1983 and 1988 at 904 hospitals with cancer programs. Among a total of 12,316 cases, 5156 patients had long-term survival data., Results: The overall 5-year survivals were 88.9 +/- 0.9%; 57.1 +/- 2.4%; 23.8 +/- 1.3%; and 11.6 +/- 0.9% for Stages I, II, III, and IV, respectively. Pairwise survival comparisons using Lee-Desu statistic confirmed the prognostic value of current staging system (P < 0.00001). When survival data was substratified further to substage division, the 5-year survivals were: IA, 92.1 +/- 0.9%; IB, 84.9 +/- 3.4%; IC, 82.4 +/- 2.0%; IIA, 69.0 +/- 4.3%; IIB, 56.4 +/- 3.6%; IIC, 51.4 +/- 4.5%; IIIA, 39.3 +/- 2.8%; IIIB, 25.5 +/- 2.6%; IIIC, 17.1 +/- 1.4%; and IV, 11.6 +/- 0.9%. As the disease process becomes more advanced, patients' survival reduces proportionally. However, the survival reduction is relatively small between IB-IC and IIB-IIC divisions. Survival comparisons revealed significant prognostic value for most substage divisions (P = 0.03-0.0002) except for IB-IC and IIB-IIC combinations (P > 0.33). Further analyses revealed no significant differences between IB-IC and IIB-IIC patients in several prognostic parameters such as age, histologic grade, cell type, and amount of residual disease., Conclusions: These data support the current FIGO staging system. However, Substages IB-IC and IIB-IIC should be combined to respective single substages.

Most patients with ovarian cancer currently are treated primarily with surgery and chemotherapy. Drug selection usually is not based on individualized in vitro sensitivity studies but on reported response rates of clinical trials. Attempts to include in vitro chemosensitivity testing into the management of ovarian cancer have been disappointing to clinicians. Tumor cells from fresh human ovarian cancer do not grow well under artificial in vitro growth conditions. The selection of cells that happen to proliferate in vitro (e.g., human tumor clonogenic assay) has resulted in low plating efficiencies (0.001-0.1% of plated cells). The vigorous mechanical and enzymatic tumor disaggregation, done to obtain a single-cell suspension, further reduces the number of cells that grow in vitro, resulting in low overall evaluability rates of 40-70% for the human tumor clonogenic assay. At the University of Miami, a new in vitro chemosensitivity assay was developed that detected the decrease in total tumor cell viability by measuring intracellular adenosine triphosphate as a function of in vitro drug response. Preliminary data on 31 tumor tissues from patients, which was evaluated with this method, showed a sensitivity of 92% and a specificity of 100%. Since these initial studies, data were gathered on more than 150 fresh gynecologic tumor specimens to evaluate single drugs and drug combinations at five concentrations (range, 10-500% of reported peak plasma concentrations). The evaluability rate for ovarian tumors was more than 90%. Some tumors showed almost complete cell kill at the lowest drug concentration; others had only a limited response at the highest level. Drug-response patterns also were variable for combined drug exposure. These findings underscore the heterogeneity of drug response in morphologically similar tumors and the importance of characterizing individual chemosensitivity profiles for patients before drug treatment.