Impact of uterine manipulator on oncological outcome in endometrial cancer surgery

Background: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. Objective: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. Study Design: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. Results: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27–4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I–II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57–0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07–2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). Conclusion: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I–II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results

Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer

Purpose: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. Patients and Methods: patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m2/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. Results: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P = .025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P < .001), nausea or vomiting (P = .003), and fever without documented infection (P = .007), and less hospitalization for febrile neutropenia than did CMFP (P = .001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P < .0001). Overall, quality of life was similar for both treatments (P greater than or equal to .07). Conclusion: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP. (C) 1999 by American Society of Clinical Oncology

Drugs Against Protozoan Parasites: Target Selection, Structural Biology and Medicinal Chemistry, Copper Mountain, CO, USA, 9-13 April 2005

The International meeting on Drugs against protozoan parasites is organized regularly every three years. This time the Congress, organized by Margaret A.Phillips, Pradipsinh K.Rathod and William N.Hunter, has been held in Copper Mountain Resort and is part of the Keystone symposia series. It was appropriately structured as a multidisciplinary approach to the problem of Drug discovery and development against neglected diseases. Top-ranking scientist from the different areas of functional genomics, structural biology, medicinal chemistry and clinical development had the opportunity to meet and actively discuss of the most important issues related to the field of Malaria, African trypanosomiasis and Leishmaniasis such as new drug targets identification, lacking of “shuttle funding” from lead discovery identification to clinical phases evaluation, funding opportunities from the pharmaceutical companies and govern involvement. The crucial issue of intellectual property and effective cost of the final treatment was discussed. A discrete portfolio of candidate drug, with respect to the past, is at the moment entering the clinical phase III, but most of the new chemical entities are still at the lead level or phase I and II. Among the recent compounds on the market Cancidas, Chlorproguanildapsone, (Lapdap™), Artesunate(CDA) Pediatri, in Phase I, II and III Artekin ™ (dihydroartemisinin-piperaquine), Coartem™ (MMV). The sessions dedicated to the clinical trials and details on the phase I-III were missed, and many problems to the practical approach to the clinical phase evaluation were raised