Abstract: INTRODUCTION: Hysteroscopy is a diagnostic procedure with a high accuracy in diagnosing endometrial cancer. Because of the increase of intrauterine pressure during distention media inflation, several retrospective studies postulated that it may result in cancer cell dissemination within the peritoneal cavity through the fallopian tubes. We therefore set to estimate whether hysteroscopy increases the risk for intraperitoneal cancer cell dissemination in patients with endometrial cancer and the risk of disease upstaging in patients with clinically early-stage disease. METHODS: We searched the PubMed, the ISI Web of Science, and the Cochrane Library through July 2009. Eligible trials were all controlled clinical trials in which patients were allocated to hysteroscopy (alone or after other diagnostic procedure, eg, dilation and curettage and biopsy) versus any other diagnostic procedure except hysteroscopy or no procedure before surgery for endometrial carcinoma. RESULTS: Nine trials were included in our analysis. One thousand fifteen patients with histologically proven endometrial carcinoma were allocated to hysteroscopy or no hysteroscopy before surgery. Hysteroscopy resulted in a significantly higher rate of malignant peritoneal cytology (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.13-2.79; P = 0.013) and significantly higher disease upstaging owing solely to the presence of malignant cells in the peritoneal cavity (OR, 2.61; 95% CI, 1.47-4.63; P = 0.001) compared with no hysteroscopy. When isotonic sodium chloride was used as distention medium, hysteroscopy resulted in a statistically significant higher rate of malignant peritoneal cytology (OR, 2.89; 95% CI, 1.48-5.64; P = 0.002), whereas a nonsignificant trend for higher malignant cells was observed in patients allocated to the hysteroscopy group (OR, 3.23; 95% CI, 0.94-11.09; P = 0.062) when inflated media pressure reached or exceeded 100 mm Hg. CONCLUSIONS: Hysteroscopy in patients with endometrial cancer hints a risk for cancer cell dissemination within the peritoneal cavity. Prospective and sufficiently powered trials are needed to clarify whether the risk of cancer cell spreading is correlated with worse prognosis.
Abstract: PURPOSE: To compare efficacy and tolerability of fulvestrant with aromatase inhibitors and tamoxifen that actually represent the standard of care in hormone-sensitive breast cancer. METHODS: Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, time to progression, clinical outcome and objective response. Secondary outcome was the tolerability profile of the drugs. RESULTS: Four trials were identified with 2125 eligible patients. There was no statistically significant difference between fulvestrant and other hormonal agents in terms of overall survival (pooled HR: 1.047, 95% CI: 0.688-1.592), time to progression (pooled HR: 0.994, 95% CI: 0.691-1.431), clinical benefit (pooled OR: 1.044, 95% CI: 0.828-1.315) or objective response rate (pooled OR: 0.949, 95% CI: 0.736-1.224). A higher incidence of joint disorders (pooled OR: 0.621, 95% CI: 0.424-0.909; P=0.014) was noted in patients receiving hormonal agents other than fulvestrant. CONCLUSION: Fulvestrant was similar to other hormonal agents with respect to efficacy measures, with good tolerability profile.
Abstract: OBJECTIVE: To investigate whether vaginal progesterone gel may result in similar or higher pregnancy rates compared with all other vaginal progesterone forms when used for luteal-phase support. DESIGN: Meta-analysis of randomized controlled trials using odds ratios (OR) and 95% confidence intervals (CI). PATIENT(S): Infertile women undergoing IVF or ICSI. INTERVENTION(S): Vaginal progesterone gel 90mg once or twice daily versus any other vaginal progesterone form for luteal phase support. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Seven randomized controlled trials, involving 2,447 patients, were included in the analysis. No difference was observed in the overall clinical pregnancy rate when comparing vaginal progesterone gel with any other vaginal progesterone form. Moreover, clinical pregnancy rates were similar in protocols using only GnRH agonists and when comparing vaginal gel with the traditional treatment of 200 mg x 3 vaginal progesterone capsules. CONCLUSION(S): This meta-analysis provides solid evidence that no significant difference exists between vaginal gel and all other vaginal progesterone forms in terms of clinical pregnancy rates.
Abstract: To address whether the use of bisphosphonates in the adjuvant setting of breast cancer might have any effect on the natural course of the disease, a meta-analysis was conducted of published and unpublished randomized controlled trials found in PubMed, the Cochrane Central Register of Controlled Trials, the ISI Web of Knowledge, and abstracts of major international conferences up to January 2009. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with any bisphosphonate versus non-use were considered eligible. Analysis included data from 13 eligible trials involving 6886 patients randomized to treatment with bisphosphonates (n = 3414) or either placebo or no treatment (n = 3472). Compared with no use, adjuvant breast cancer treatment with bisphosphonates did not reduce the overall number of deaths (odds ratio [OR], 0.708; 95% CI, 0.482-1.041; P = .079), bone metastases (OR, 0.925; 95% CI, 0.768-1.114; P = .413), overall disease recurrences (OR, 0.843; 95% CI, 0.602-1.181; P = .321), distant relapse (OR, 0.896; 95% CI, 0.674-1.192; P = .453), visceral recurrences (OR, 1.051; 95% CI, 0.686-1.609; P = .820), or local relapses (OR, 1.056; 95% CI, 0.750-1.487; P = .756). No significant heterogeneity was observed among the trials except for estimates of deaths and disease recurrences (P = .034 and P = .016, respectively). In subgroup analyses, use of zoledronic acid was associated with a statistically significant lower risk for disease recurrence (OR, 0.675; 95% CI, 0.479-0.952; P = .025). However, these results should be interpreted with caution because the statistical significance for this association was weak and might be attributed to chance from multi-test analyses. Use of zoledronic acid was not associated with any significant difference in death (OR, 0.642; 95% CI, 0.388-1.063) and bone metastasis rates (OR, 0.661; 95% CI, 0.379-1.151). Currently available evidence does not support the hypothesis that use of bisphosphonates in adjuvant treatment of early breast cancer will alter the natural course of the disease. Nonetheless, a nonsignificant trend seems to exist for better outcomes in patients undergoing bisphosphonate treatment. Until further evidence from new clinical trials becomes available, adjuvant bisphosphonates should not be recommended routinely.
Abstract: The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast-radiation therapy (WBRT). We conducted a systematic review and meta-analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674-1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506-1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278-7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396-3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058-5.715; p < 0.0001) compared with whole breast-radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast-radiation. Nevertheless the issue of loco-regional recurrence needs to be further addressed.
Abstract: OBJECTIVES: Recent data suggest that fractures might affect quality of life and survival in early breast cancer patients. Bisphosphonates are effective in treatment and prevention of cancer treatment-induced bone loss, but their value in the prevention of fractures is still investigational. Our aim was to evaluate the fracture rate in breast cancer patients receiving adjuvant bisphosphonates compared with those receiving no treatment or placebo. METHODS: Our study is a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library and major cancer scientific meetings searches. We identified 21 potentially eligible trials. Of these, 14 studies reported fracture data and were included in the analyses. Overall, 7461 early breast cancer patients were randomized, 3691 received bisphosphonates and 3770 received either placebo or no treatment. RESULTS: Adjuvant breast cancer treatment with bisphosphonates did not reduce the fracture rate compared to placebo or no use either in intent to treat analysis (12 trials, OR=0.99, 95% CI=0.73-1.34, p=0.932) and in comprehensive analysis (all 14 trials included, OR=0.84, 95% CI=0.65-1.09 p=0.197). Treatment with bisphosphonates was not beneficial in postmenopausal patients (7 trials, OR=0.82, 95% CI=0.55-1.20 p=0.298) and in patients receiving aromatase inhibitors (6 trials, OR=0.79, 95% CI=0.53-1.17 p=0.242). CONCLUSION: Our meta-analysis provides substantial evidence that bisphosphonates in the adjuvant setting among women with breast cancer do not decrease the number of fractures compared with placebo or no treatment.
Abstract: Numerous studies have demonstrated that angiogenesis and in particular VEGF over-expression play an essential role in the progression and metastatic potential of breast cancer. Bevacizumab is a humanized recombinant monoclonal antibody that specifically blocks the binding of VEGF to high-affinity receptors and it has been recently used for the treatment of metastatic breast cancer. We conducted a meta-analysis to synthesize available evidence for use of bevacizumab in metastatic breast cancer patients. Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, progression free survival (PFS) and objective response rate (ORR). Five trials were identified with 3,163 eligible patients. Combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in PFS (HR = 0.70, 95% CI 0.60-0.82, P = 9.3 x 10(-6)) and ORR (RR = 1.26, 95% CI 1.17-1.37, P = 9.96 x 10(-9)) compared with chemotherapy alone. Differences in objective response rates were substantial independently by the type of chemotherapy used, while PFS advantages were observed only for taxanes. The pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (HR = 0.90, 95% CI 0.80-1.03, P = 0.119). This meta-analysis shows that the addition of bevacizumab to chemotherapy offers meaningful improvement in PFS and ORR in patients with metastatic breast cancer. Bevacizumab treatment might be suggested for treatment of 1st line metastatic breast cancer, but more data are needed until statistical overall survival differences will be documented and firm guideline recommendation could be given.
Abstract: More than 3days' luteal endometrial advancement in IVF has been related with no pregnancies. This study assessed the effect of recombinant and urinary human chorionic gonadotrophin (recHCG and uHCG) when administered for final oocyte maturation on the advancement of endometrial histology. Thirty patients were randomized to receive either 250mug recHCG or 10,000IU uHCG in an antagonist/recombinant FSH protocol. Endometrial biopsy was performed on the day of oocyte retrieval. All specimens were evaluated according to Noyes' criteria by one pathologist blinded to the allocation treatment groups. Single blastocyst transfer was performed. Overall, 13 patients in recHCG group and 14 patients in uHCG group underwent endometrial biopsy. The mean days of histological endometrial advancement were comparable between the two groups: 2.03 versus 2.17days, respectively. Nevertheless more patients (69%, 9/13) had less than 3days' advanced endometrium in the recHCG arm as compared with 43% (6/14) patients in the uHCG group (OR 3.00, 95% CI 0.4-16.3). The delivery rate per patient was higher, although not significantly, in the recHCG group (38.5% versus 28.6%). Both recHCG and uHCG preparations induce advancement of endometrial maturation. Whether a subtle difference in endometrial maturation affects the reproductive outcome remains to be proven.
Abstract: In a prospective randomized controlled trial, 119 patients were randomized to receive either recombinant hCG (250 mug) or urinary-derived hCG (10,000 IU) for final oocyte maturation in an antagonist protocol with a fixed dose of recombinant FSH (187.5 IU) and predefined single blastocyst transfer. The delivery rate was improved in the recombinant hCG group compared with the urinary-derived hCG group (44.1 vs. 25.7, respectively); however, adequately powered randomized controlled trials are justified to ascertain whether this difference is true.
Abstract: BACKGROUND: Taxanes have been extensively tested in patients with advanced breast cancer, but it is unclear whether their weekly use might offer any benefits against standard every three weeks administration. We therefore performed a meta-analysis of randomized controlled trials that compared weekly and every three weeks taxanes regimens in advanced breast cancer. METHODS: The endpoints that we assessed were objective response rate, progression free survival (PFS) and overall survival. Efficacy data for paclitaxel and docetaxel were separately analyzed. Trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. RESULTS: Omicronbjective response rate was notably better when paclitaxel was used as every three weeks regimen (7 studies, 1772 patients, fixed effect model pooled RR 1.20 95%CI 1.08-1.32 p<0.001). No difference were found for PFS (6 studies, 1610 patients, random effect model HR 1.02, 95%CI 0.81-1.30 p=0.860); while OS was statistically higher among patients receiving weekly paclitaxel (5 studies, 1471 patients, fixed effect model pooled HR 0.78, 95%CI 0.67-0.89 p=0.001). No differences were observed for the weekly compared to the every three weeks use of docetaxel either for objective response, PFS and OS. Overall, the incidence of serious adverse events, neutropenia, neutropenic fever, and peripheral neuropathy were significantly lower in weekly taxanes schedules. The incidence of nail changes and epiphora were significantly lower in the every three weeks docetaxel regimens. CONCLUSIONS: Use of paclitaxel in weekly regimen give overall survival advantages compared with the standard every three weeks regimen. The observed survival benefit does not seem to stem from an increased potency of the drug with weekly regimens. The use of weekly paclitaxel regimens is therefore recommended for the treatment of locally advanced/metastatic breast cancer.
Abstract: We conducted a metaanalysis of randomized controlled trials to determine whether periodontal disease treatment with scaling and/or root planing during pregnancy may reduce preterm birth (PTB) or low birthweight (LBW) infant incidence. Treatment resulted in significantly lower PTB (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.35-0.86; P = .008) and borderline significantly lower LBW (OR, 0.48; 95% CI, 0.23-1.00; P = .049), whereas no difference was found for spontaneous abortion/stillbirth (OR, 0.73; 95% CI, 0.41-1.31; P = .292). Subgroup analysis suggested significant effect of treatment in the absence of history of PTB or LBW (OR, 0.48; 95% CI, 0.29-0.77; P = .003) and less severe periodontal disease as defined by probing depth (OR, 0.49; 95% CI, 0.28-0.87; P = .014) or bleeding on probing site (OR, 0.37; 95% CI, 0.14-0.95; P = .04). If ongoing large and well-designed randomized trials support our results, we might need to reassess current practice or at least be cautious prior to rejecting treatment of periodontal disease with scaling and/or root planing during pregnancy.
Abstract: PURPOSE: To estimate cancer screening coverage among a large sample of Greek individuals. METHODS: 7012 adults from 30 Hellenic areas were surveyed. Tests included: faecal occult blood test, sigmoidoscopy,chest X-ray, urine test, testicular examination,trans-rectal ultrasound, full blood count, skin examination,digital rectal examination, PSA, Pap test, mammography,clinical breast examination (CBE), self breast examination and breast ultrasound. RESULTS: Eighty-eight percent of males and 93% of females declared being interested in cancer screening; 37.8% of men and 37.9% of women had had a medical consultation for screening purpose in the previous 2 years. Less than 2%reported having received screening for colorectal cancer or skin malignancies. Screening for cervical cancer, mammography and CBE was reported by 39.6%, 22.8% and 27.9% of females respectively. Twenty percent of males reported screening for prostate cancer. CONCLUSION: The actual opportunistic screening approach presents important deficiencies with displaced priorities in test performance and a low proportion of individuals undergoing recommended tests.
Abstract: OBJECTIVE: To assess whether the proportion of primary care physicians implementing full body skin examination (FBSE) to screen for melanoma changed over time. METHODS: Meta-regression analyses of available data. Data Sources: MEDLINE, ISI, Cochrane Central Register of Controlled Trials. RESULTS: Fifteen studies surveying 10,336 physicians were included in the analyses. Overall, 15%-82% of them reported to perform FBSE to screen for melanoma. The proportion of physicians using FBSE screening tended to decrease by 1.72% per year (P =0.086). Corresponding annual changes in European, North American, and Australian settings were -0.68% (P =0.494), -2.02% (P =0.044), and +2.59% (P =0.010), respectively. Changes were not influenced by national guide-lines. CONCLUSIONS: Considering the increasing incidence of melanoma and other skin malignancies, as well as their relative potential consequences, the FBSE implementation time-trend we retrieved should be considered a worrisome phenomenon.
Abstract: Central venous catheters (CVCs) are commonly used for the administration of intravenous chemotherapy in outpatient setting. Nevertheless, outbreaks of catheter-associated bloodstream infections had been reported from oncology centers. We describe a large outbreak of CVCs-associated Klebsiella oxytoca bloodstream infection, occurring in an oncology chemotherapy outpatient unit of northern Greece between October 2006 and May 2007. The outbreak involved approximately 10% of the patients with CVCs who were receiving home-based chemotherapy, and it represents the second larger outbreak of CVCs-associated BSIs due to Klebsiella oxytoca in oncology outpatient centers. We retrospectively analyzed the chain of investigations and prophylactic/diagnostic measures taken to eradicate the infection: (1) patients' chart audit, (2) estimation of the infection among asymptomatic patients, (3) implementation of the level of awareness of medical and paramedical personnel, (4) collection of samples from environment, medications and infusion materials, (5) critical appraisal of chemotherapeutical schemes and (6) cooperation with peripheral institutions. The isolation of Klebsiella oxytoca in a chemotherapy solution (infusional 5-FU in dextrose 5% solution within a 48 h pump) from a peripheral General Hospital and the prompt transmission of the data to the chemotherapy center played a key role for the management of the infection cluster. This is the first report that evidenced the detection of Klebsiella oxytoca within a chemotherapeutical preparation. Data transmission from peripheral hospitals to the central institution resulted in an important feedback that allowed a better estimation of the infection cluster and more tailored actions for the eradication of the infection.
Abstract: Ovulation induction remains a milestone in the treatment of women with anovulatory infertility. Clomiphene citrate (CC) is considered the first line treatment for induction of ovulation in women with polycystic ovary syndrome (PCOS), while it may be used for ovulation induction in unexplained infertility. Aromatase inhibitors (AI) have been introduced as a new treatment option that could challenge CC for ovulation induction. A systematic review of the literature was conducted in order to highlight the efficacy and safety of AI in female infertility. Current data from randomized and non-randomized trials suggest that AI may have a role in ovulation induction regimens in PCOS patients, as well as for ovarian stimulation, since they achieve comparable clinical pregnancy rates to CC. Furthermore, when combined with gonadotrophins, AI improve the ovarian response of poor responders and reduce the gonadotrophin dose required. However, the current review is based on small trials with a limited number of patients. If solid data from future large adequately powered randomized trials support current evidence regarding efficacy and safety, AI might offer a new treatment choice for infertile women.
Abstract: Recurrent miscarriage is the loss of two or more consecutive pregnancies and affects 1% of couples trying to conceive. It has proven to be frustrating for both patient and clinician. The majority of investigations and treatments offered remain controversial. However, practice must be evidence based and unproven investigations and treatments should be abandoned. Psychological support is of paramount importance since a significant number of women attending RM clinics have high levels of anxiety or are clinically depressed. Setting up a RM clinic is important to provide a dedicated service to couples with RM so as to avoid unnecessary and potentially harmful treatments, and also to recruit patients in trials that will delineate causes and efficacy of treatments.
Abstract: BACKGROUND: Many systemic nonhormonal regimens have been evaluated across several hundreds of randomized trials in advanced breast cancer. We aimed to quantify the relative merits of these regimens in prolonging survival. METHODS: We performed a systematic review of all trials that compared different regimens involving chemotherapy and/or targeted therapy in advanced breast cancer (1973-2007). Regimens were categorized a priori into different treatment types. We performed multiple-treatments meta-analysis and calculated hazard ratios for each treatment category relative to monotherapy with old agents (ie, regimens not including anthracyclines, anthracenediones, vinorelbine, gemcitabine, capecitabine, taxanes, marimastat, thalidomide, trastuzumab, lapatinib, or bevacizumab). RESULTS: We identified 370 eligible randomized trials (54,189 patients), of which 172 (31,552 patients) compared different types of treatment. Survival data from 148 comparisons pertaining to 128 of the 172 trials (26,031 patients, 22 different types of treatment) were available for inclusion in the multiple-treatments meta-analysis. Compared with single-agent chemotherapy with old nonanthracycline drugs, anthracycline regimens achieved 22%-33% relative risk reductions in mortality (ie, hazard ratio [HR] for standard-dose anthracycline-based combination: 0.67, 95% credibility interval [CrI] 0.57-0.78). Several newer regimens achieved further benefits (eg, HR [95% CrI] 0.67 [0.55-0.81] for single-drug taxane, 0.64 [0.53-0.78] for combination of anthracyclines with taxane, 0.49 [0.37-0.67] for taxane-based combination with capecitabine or gemcitabine), and similar benefits were seen with several regimens including molecular targeted treatments. Most regimens had very similar efficacy profiles (<5% difference in HR) as first- and subsequent-line therapies. CONCLUSIONS: Stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer. Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles.
Abstract: A meta-analysis of four trials showed significant advantage in pregnancy and delivery rates with aromatase inhibitors compared with CC in women with PCOS. A recent randomized trial demonstrated no clear benefit.
Abstract: Treatment of unexplained infertility is empiric and different regimens or protocols have been used so far. Clomiphene can be used alone or combined with gonadotrophins. Aromatase inhibitors may offer an alternative for first-line treatment. To compare the efficacy of aromatase inhibitors versus climiphene, we conducted a systematic review and meta-analysis for randomized controlled trials comparing the above regimens to estimate live pregnancy rates in women with unexplained infertility. Trials were located through PubMed and Cochrane Library searches. Methodological quality of included trials has been assessed. Then, 2 x 2 tables were constructed, and pooled odds ratios (ORs) were calculated. Ten arms (273 patients) were included in the meta-analysis. ORs were homogeneous between studies (heterogeneity chi2 = 2.33, P = 0.676). No difference was observed for live pregnancies (pooled OR 0.87, 95% CI, 0.46-1.65, P = 0.666) for aromatase inhibitors versus clomiphene citrate; however, the definition of live pregnancy by the authors was clear only in one trial. Data regarding secondary outcomes were omitted, and methodogical quality of eligible trials did not reach high scores. Evidence from randomized data regarding the use of aromatase inhibitors is fragmented and weak. Aromatase inhibitors may have a role in the treatment of women with unexplained infertility desiring pregnancy. However, meticulous reporting and study design should be a priority in this field and large, registered, and properly designed randomized trials are essential to test whether aromatase inhibitors can be introduced as a first-line treatment in carefully selected subgroups of women with unexplained infertility.
Abstract: BACKGROUND AND AIMS: Colorectal cancer is a major cause of cancer death in European countries and differences in screening implementation may in part explain USA vs European survival differences. Despite the evidence, no study has evaluated the population colorectal cancer screening (CCS) coverage in any European country. We aimed to index the current CCS practices among a large sample of Greek healthy adults. MATERIALS AND METHODS: The study was designed as a cross-sectional survey. Screening practice habits of 5,259 healthy adults, aged 50-80, were surveyed. Both overall and screening practices of stool occult blood test (SOBT), digital rectal examination (DRE), and colonoscopy or sigmoidoscopy (COL/SIG) were analyzed. RESULTS: Of the population analyzed, 90.1% declared that they were interested in cancer prevention activities. Overall SOBT practice rate within the last 2 years was 4.77%. When only screening procedures were analyzed, this percentage shrank to 1.73%. Overall and screening COL/SIG rates within the last 10 years were 8.76 and 1.74%, respectively. The respective proportions of individuals who underwent DRE were 14.54 and 5.2%. Evidence-based screening practices were influenced by age, family history of colorectal cancer, profession, and educational level; however, SOBT and colonoscopy/sigmoidoscopy did not overcome 4.1 and 4.6% in any subpopulation analyzed. CONCLUSION: The level of CCS coverage among the examined sample of Greek adults was discouraging. Surveys among other European countries are encouraged.
Abstract: The effect of combined vitamin C and E supplementation during pregnancy on the prevention of preeclampsia and major adverse infant outcomes has been reviewed. We searched MEDLINE and the Central Library of Controlled Trials of the Cochrane Library through August 2006 for relevant clinical trials. Interstudy heterogeneity was evaluated using the chi(2) statistic (Q statistic) test. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a fixed or random-effects model as appropriate. Four trials that collectively randomized 4680 pregnant women to either the combination of vitamin C and vitamin E or placebo were included in the analysis. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia, 11% versus 11.4%, RR 0.97 (95% CI 0.82-1.13), fetal or neonatal loss, 2.6% versus 2.3%, RR 1.10 (95% CI 0.78-1.57), or small for gestational age (SGA) infant, 20.6% versus 20%, RR 0.94 (95% CI 0.74-1.19). Although there was a higher risk for preterm birth in the vitamin group, 19.5% versus 18%, RR 1.07 (95% CI 0.96-1.20), this finding was not significant. Combined vitamin C and E supplementation during pregnancy does not reduce the risk of preeclampsia, fetal or neonatal loss, small for gestational age infant, or preterm birth. Such supplementation should be discouraged unless solid supporting data from randomized trials become available. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that many methods have been used to prevent preeclampsia, state that increased oxidative stress has been postulated and many trials have used antioxidants to prevent the disease, and explain that MEDLINE analysis of the literature questions the use of vitamin C and E supplements.
Abstract: We examined the interpretation of research findings and public availability of transparent information on data and processing for 46 articles of microarray studies that had addressed major cancer outcomes. Unsupervised and supervised methods selected molecular signatures with a median of 675 and 50 genes, respectively, but only a median of eight genes or groups thereof were further discussed. Across 479 genes or groups thereof discussed in all 46 studies, 65% reflected specific comments (reflecting external relevant data from other studies or other lines of reasoning relevant to the gene of interest), and 59% of the comments were referenced. Among specific comments, supportive ones outnumbered comments against the research findings by nine to one (270 versus 29). Discussion was similarly selective in early studies and in studies published in 2006. Even in 2006 only 10 of 15 studies had publicly deposited data. Only three studies had scanned images, raw and processed data available. Processing details varied. Public transparency and unbiased interpretation of findings can be improved in microarray research.
Abstract: Genital Chlamydia trachomatis infection is the principal cause of bacterial sexually transmitted disease in industrialized countries. A wide spectrum of pathologic conditions has been associated with the disease ranging from urethritis, cervicitis, to pelvic inflammatory disease, ectopic pregnancy, tubal infertility and cervical neoplasia. Screening for genital Chlamydia infection may prevent its serious complications. The need of a comprehensive European screening policy has been recently underlined by PACMeR's scientific committee. Anyhow invitational screening programs are only at the beginning. Chlamydia trachomatis control ''orphan'' and women's health at risk. Until organized programs are developed, implementation of opportunistic screening is mandatory. Since the infection is more commonly observed among juvenile females proper testing of the young women is recommended. As asymptomatic young women in reproductive age are more eager to visit gynaecologists for periodical gynaecological examination and councelling (cervical cytology, breast examination, contraception and family planning), gynaecologist represents the only specialist able to provide early diagnosis of Chlamydia trachomatis. Gynaecologists are called to play a new role in public healthcare, being ''gatekeepers'' for the early detection of the disease, emphasizing their crucial part in young women's health.
Abstract: Heavy menstrual bleeding (HMB) occurs in a considerable percentage of the general population and is one of the main causes due to which a patient is referred to health services. Despite the efforts for pharmaceutical interventions, the symptom usually persists, therefore operative techniques are needed to control the bleeding. Today, apart from the choice of hysterectomy, other less aggressive techniques have been invented. The first results of the Greek Study Group on Gynecological Endoscopy regarding the use of the Thermachoice device are hereby presented. One hundred patients suffering HMB were treated with the Thermachoice device following a standard protocol designed by the Study Group. The follow-up meetings with the patients were held at 3, 6, 12, 24, and 36 months. It seems that the overall effectiveness rate (96%) is satisfactory and it is similar to the overall effectiveness rate reported in other relevant studies upon the Thermachoice device.
Abstract: The term hysteroscopy is used to determine the procedure during which an endoscopic view of the endometrial cavity is achieved with the help of a type of endoscopic device called "the hysteroscope." Hysteroscopy is used to assist the diagnosis for a series of female pathology. Apart from its diagnostic value, hysteroscopy can also be used for operative procedures including ablation and resection. Both diagnostic and operative hysteroscopy have been used for a number of years and various studies have been published to describe their success and complication rates throughout this period. Diagnostic hysteroscopy is relatively safe, whereas complications occur more frequently when operative hysteroscopy is used. These complications include uterine perforation, hemorrhage, fluid overload, gas embolization, and hyponatremia. The rate in the appearance of these complications is dependent on the type of the hysteroscopic procedure, the distending medium, and the experience of the hysteroscopist. To avoid any problems concerning the application of hysteroscopic procedures, it is important to take the necessary precautions both preoperatively and intraoperatively. For example, the preoperative use of thinning agents of the endometrium and the reduction of the operating time, or the avoidance of cutting too deeply into the myometrium, are some of the parameters to be considered when hysteroscopy is in argument.
Abstract: Several chemotherapy and hormonal therapy regimens have been used in advanced endometrial cancer. In this review we have systematically evaluated the available data from randomized trials on survival. We searched MEDLINE, EMBASE and the Cochrane Library (last search April 2005) for randomized controlled trials evaluating various chemotherapy or hormonal therapy regimens in locally advanced or metastatic endometrial cancer. We focused on survival outcomes and examined trial characteristics pertaining to quality and potential biases. Across 17 eligible trials (2964 patients randomized), only 4 regimens were involved in more than one trial, and only two trials had used the same comparison of regimens. A statistically significant effect in survival was seen only in one recent trial, but it was borderline (P = 0.032) and amounted to only 3 months difference in median survival. Three more trials reported some survival benefits, but these were seen only after specific adjustments, and the difference was against the experimental arm in one of these three trials. Only four trials (24%) apparently analyzed all randomized patients and none of the trials were blinded. Median survival was seemingly longer in more recent compared with older trials, but this effect was driven by the inclusion of significantly fewer patients with poor performance status in more recent trials (P < 0.001). Overall, randomized evidence on systemic treatment in advanced endometrial cancer is fragmented and survival benefits for specific regimens are questionable.
Abstract: BACKGROUND: Aromatase inhibitors and inactivators have been extensively tested in patients with advanced breast cancer, but it is unclear whether they offer any survival benefits compared with standard hormonal treatment with tamoxifen or progestagens. We performed a meta-analysis of randomized controlled trials that compared several generations of aromatase inhibitors and inactivators with standard hormonal treatment in patients with advanced breast cancer. METHODS: The endpoint that we assessed was survival. Trials were located through searches of PubMed and Cochrane Library (last update March 2006). Relative hazards (RHs) were summarized across trials through fixed- and random-effects analyses, and heterogeneity was assessed with the Q and I2 statistics. All statistical tests were two-sided. RESULTS: Twenty-five different comparisons, with a total of 8504 patients, were included in the meta-analysis. We found statistically significant survival benefits with third-generation aromatase inhibitors and inactivators (vorozole, letrozole, examestane, and anastrazole) (RH = 0.87, 95% confidence interval [CI] = 0.82 to 0.93; P<.001) but not with first-generation (aminoglutethimide) or second-generation (formestane and fadrozole) agents. The difference in the summary effects between these two groups of trials was statistically significant (P = .04). The survival benefit with third-generation agents in first-line trials, in which these agents were compared with tamoxifen (11% RH reduction, 95% CI = 1% to 19%; P = .03), was identical to their benefit in second- and subsequent-line trials in which these agents were compared with other treatments (14% RH reduction, 95% CI = 6% to 21%; P<.001). CONCLUSIONS: Inhibition of the aromatase system, in particular with third-generation aromatase inhibitors and inactivators, appears to be associated with statistically significant improved survival of patients with advanced breast cancer compared with standard hormonal treatments.
