Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors.

The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.

Adenovirus gene transfer vectors inhibit growth of lymphatic tumor metastases independent of a therapeutic transgene.

Adenovirus (Ad) gene transfer vectors traffic to regional lymph nodes (RLNs) after footpad injections in mice, resulting in localized production of interferon gamma (IFN-gamma). With this background, we evaluated the hypothesis that Ad vector administration may inhibit RLN tumor metastasis independent of the transgene in the expression cassette. Tumors of MM48, a cell line with a propensity toward lymphogenous metastasis, were established in the footpads of syngeneic C3H mice, and E1(-)E3(-) Ad vectors encoding no transgene (AdNull) or encoding an irrelevant transgene (AdCD; Escherichia coli cytosine deaminase with no 5-fluorocytosine administration) were administered (10(10) particles) in a peritumoral location. Both vectors suppressed the growth of tumor in the regional (popliteal) lymph node. This effect was localized to the regional, but not distant, lymph nodes (p < 0.05). Heat inactivation of the vector or decreasing the dose of the vector to 10(9) particles did not suppress RLN growth of the tumor when compared with 10(10) particles of active AdNull (p < 0.05 and p < 0.01, respectively). The ability of an E1(-)E4(-) vector expressing beta-galactosidase (AdRSVbetagal.11) to suppress RLN tumor growth showed that the E4 region of the Ad vector was not responsible for the effect. Blocking either IFN-gamma or natural killer (NK) cells with systemic antibody treatment in immunocompetent mice allowed rapid growth of RLN metastases despite Ad vector administration, and Ad vector injection into the footpads of tumor-free mice induced the accumulation of NK cells in the RLN. These data demonstrate that, in a metastatic murine tumor model, a low dose (10(10) particles) of replication-deficient Ad vectors inhibits RLN metastases independent of a therapeutic transgene, an effect that is mediated, at least in part, by IFN-gamma and NK cells.

Lobectomy improves ventilatory function in selected patients with severe COPD.

BACKGROUND: Patients often undergo limited resection instead of lobectomy for non-small cell lung cancer because of a low preoperative forced expiratory volume in 1 second (FEV1). Our goal is to define criteria that will preoperatively identify a group of patients who will not lose further function after lobectomy. METHODS: Patients who underwent lobectomy with a preoperative FEV1 of less than 80% of predicted were retrospectively identified. Data collected included preoperative and postoperative pulmonary function tests, age, sex, the lobe resected, and preoperative ventilation-perfusion scan result. RESULTS: Thirty-two patients were included in this study. The median preoperative FEV1 was 60% of predicted (1.65 L) and the mean change in FEV1 was a loss of 7.8% after lobectomy. The patients were divided into two groups. Group 1 (n = 13) had a preoperative FEV1 of less than or equal to 60% of predicted (median, 49%; 1.35 L) combined with an FEV1 to forced vital capacity ratio of less than or equal to 0.6. Group 2 (n = 19) includes all other patients (median preoperative FEV1, 69% of predicted; 1.87 L). The mean changes in FEV1 after lobectomy were +3.7% and -15.7% for groups 1 and 2, respectively (p < 0.005). A chronic obstructive pulmonary disease index was defined and then calculated for each patient. The relationship between this index and the change in FEV1 after lobectomy for all 32 patients appears linear (r = -0.43; p = 0.015). CONCLUSIONS: Patients with a very low preoperative FEV1 and FEV1 to forced vital capacity ratio are less likely to lose ventilatory function after lobectomy and may actually improve it.

A comparison of thromboembolic prophylaxis in gynecologic oncology patients.

The objective of this study was to compare two methods of thromboembolic prophylaxis: sequential compression devices alone (SCDs) vs. SCDs with subcutaneous low-dose unfractionated heparin (UH). A retrospective cohort study was conducted of 168 patients who had undergone surgery for suspected gynecological malignancies. These patients were examined for associated risk factors, method of prophylaxis, and incidence of clinically significant thromboembolic events. Of these patients, 94 (56%) received perioperative and postoperative sequential compression devices alone, while 74 (44%) received both SCDs and subcutaneous low-dose UH. The postoperative course of these patients, while in the hospital and after discharge, was followed for clinically evident thromboembolic complications. Univariate and multivariate analyses were performed. The two groups were comparable in terms of most risk factors, including age, stage, height, weight, body surface area, estimated blood loss, total anesthesia time, and nodal disease. Six of 94 patients (6.4%) in the SCDs group suffered from venous thromboembolism, while four of 74 patients (5.4%) who received both SCDs and low-dose UH had a thromboembolic event (chi2 P = 0.79). There was no difference in postoperative changes in platelet counts between the two groups. Heparin added additional cost, 105 extra minutes of nursing time per patient per admission, and additional pain for the patient. In conclusion, the addition of subcutaneous low-dose unfractionated heparin to SCDs for prophylaxis against deep venous thrombosis in women undergoing surgery for gynecologic malignancies does not improve the outcome. Adding heparin was more expensive, time consuming, and painful. Heparin should not be used with SCDs unless an additional benefit can be demonstrated in a randomized controlled trial.