Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

BACKGROUND: For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. METHODS: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. RESULTS: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. CONCLUSIONS: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer.

BACKGROUND: In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first 12 months (P < .0001) and then began to stabilize. CONCLUSIONS: Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck.

Analysis of Sciellin (SCEL) as a candidate gene in esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to investigate whether a candidate gene, Sciellin (SCEL), mapping to the chromosome 13q21-q31 is mutated in esophageal cancer. MATERIALS AND METHODS: The coding region and intron-exon junctions of SCEL were sequenced in 13 esophageal squamous cell cancers and matching normal esophageal samples to detect mutations. RESULTS: Three single nucleotide polymorphisms were detected in SCEL of which two were silent mutations (L640L and H654H) and one missense mutation (R366K). CONCLUSION: Single nucleotide polymorphisms were detected in both matching tumor and normal esophageal tissues but no disease-associated mutations suggesting that SCEL is not a major factor in esophageal squamous cell carcinogenesis.

Evidence-based clinical practice guidelines on some important aspects of the care of critically ill surgical patients Part II: Surgical intensive care units, implementation of guidelines

The first part of the critical care guidelines of the Philippine College of Surgeons (PCS) and supported by Glaxo Wellcome Philippines, Inc. dealt with resuscitation fluids, blood transfusion, assessment of volume resuscitation, nutritional support and cardiovascular support. The second part deals with the last 2 aspects identified by the Technical Working Group (TWG) namely: surgical intensive care units and implementation of guidelines. The literature search, limited to english publications. Used both electronic and manual methods. Three electronic databases were used: 1) The Cochrane Library, Issue 4, 2000; 2) National Library of Medicine - Medline (PubMed, no time limit): and HERDIN (Health Research and Development Information Network) Version 1, 1997 of DOST-PCHRD. Manual searching of the reference lists of review articles and some important meta-analyses and randomized controlled trials (RCTs) was also done. The search terms used were: 1) Cochrane library: surgical intensive care, guidelines implementation, 2) Medline: surgical intensive care, 3) HERDIN: intensive care. Titles of all articles were printed and all members of the TWG went over the list and checked the titles of articles whose abstracts they felt should be read. The abstracts of all checked articles were printed. The printed abstracts were given to the members, who then decided which articles were to be included for full text retrieval. The full texts were obtained from the University of the Philippines Manila Library, and were appraised using standard forms. (Author)