Prognostic value of preoperative hyponatremia and thrombocytosis in patients with epithelial ovarian cancer.

BACKGROUND: Preoperative hyponatremia and thrombocytosis are associated with perioperative morbidity in patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate preoperative hyponatremia and thrombocytosis as prognostic parameters in patients with EOC. METHODS: In a retrospective cohort study, serum levels of sodium and thrombocyte counts were evaluated in 498 patients with EOC. Data were extracted from the prospectively maintained database. Results were correlated with clinicopathological parameters and patient survival. RESULTS: Mean (standard deviation) overall pretherapeutic serum sodium levels and thrombocyte counts in patients with EOC were 138.8 (2.9) mmol/l and 340.1 (122.6)â€¯× 103/µl, respectively. Hyponatremia (serum sodium levels ≤ 134 mmol/l) was found in 33 (6.7%) patients and thrombocytosis (thrombocytes ≥ 450/µl) in 88 (17.7%) patients. Serum sodium levels were associated with the presence or absence of residual tumor tissue after primary surgery. Thrombocyte counts were associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) tumor stage, presence/absence of residual tumor, histological grade and histological type. Patients with thrombocytosis presented with advanced tumor stage, a higher rate of postoperative residual tumor mass, higher tumor grade, and a higher rate of serous ovarian cancer. In a multivariate logistic regression analysis, only the established clinicopathological parameters but not serum sodium and thrombocyte count were independent predictors of patient overall survival. CONCLUSION: Preoperative hyponatremia and thrombocytosis are not useful as additional independent prognostic parameters in patients with EOC.

Prognostic Value of Serum Creatinine Levels in Patients with Epithelial Ovarian Cancer.

AIM: To evaluate preoperative serum creatinine level as a prognostic parameter in patients with primary epithelial ovarian cancer (EOC). PATIENTS AND METHODS: In a retrospective cohort study, serum levels of creatinine were evaluated in 498 patients with EOC. Data were extracted from our prospectively maintained database. Results were correlated with clinicopathological parameters and patient survival. RESULTS: The mean pre-therapeutic serum creatinine level in patients with EOC was 0.84±0.40 mg/dI. A serum creatinine level of 1.2 mg/dl or higher was found in 22 (4.4%) patients and associated with poor survival. In a multivariate logistic regression analysis, the serum creatinine level was a significant independent prognostic parameter of overall survival. CONCLUSION: The preoperative serum level of creatinine may be useful as an additional independent prognostic parameter in patients with EOC.

Paget's Disease of the Vulva Treated with Imiquimod: Case Report and Systematic Review of the Literature.

BACKGROUND: Extramammary Paget's disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular growth pattern. Adjuvant treatment with the immunomodulator imiquimod may be suitable to avoid repeated and mutilating surgery. CASE PRESENTATION: We present the case of a 73-year-old woman with EPDV, initially treated with surgical resection and re-resection for involved margins. Final histology revealed Paget's disease of the left vulva with 8 cm in the largest diameter and again involved margins. Subsequently, topical therapy with imiquimod 5% cream twice weekly was applied for 3 months. Vulvoscopy and local biopsies confirmed complete remission (CR). Based on a literature search using PubMed and the Cochrane Central Register of Controlled Trials, 21 reports on the therapeutic efficacy of imiquimod in 70 women with EPDV have been published. Pooled rates of CR and partial remission were 71% (50/70) and 16% (11/70), respectively. There were 4 cases of disease progression under imiquimod and the therapy was generally well tolerated with mild to moderate local reactions in >50% of cases. CONCLUSION: EPDV is a rare genital neoplasia and may be successfully treated with the topical immunomodulator imiquimod. Specifically, adjuvant imiquimod is a feasible and efficacious treatment option for women with involved resection margins after surgery.

Dynamic changes of tumor gene expression during repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with peritoneal cancer.

BACKGROUND: Intraperitoneal chemotherapy is used to treat peritoneal cancer. The pattern of gene expression changes of peritoneal cancer during intraperitoneal chemotherapy has not been studied before. Pressurized intraperitoneal aerosol chemotherapy is a new form of intraperitoneal chemotherapy using repeated applications and allowing repeated tumor sampling during chemotherapy. Here, we present the analysis of gene expression changes during pressurized intraperitoneal aerosol chemotherapy with doxorubicin and cisplatin using a 22-gene panel. METHODS: Total RNA was extracted from 152 PC samples obtained from 63 patients in up to six cycles of intraperitoneal chemotherapy. Quantitative real-time PCR was used to determine the gene expression levels. For select genes, immunohistochemistry was used to verify gene expression changes observed on the transcript level on the protein level. Observed (changes in) expression levels were correlated with clinical outcomes. RESULTS: Gene expression profiles differed significantly between peritoneal cancer and non- peritoneal cancer samples and between ascites-producing and non ascites-producing peritoneal cancers. Changes of gene expression patterns during repeated intraperitoneal chemotherapy cycles were prognostic of overall survival, suggesting a molecular tumor response of peritoneal cancer. Specifically, downregulation of the whole gene panel during intraperitoneal chemotherapy was associated with better treatment response and survival. CONCLUSIONS: In summary, molecular changes of peritoneal cancer during pressurized intraperitoneal aerosol chemotherapy can be documented and may be used to refine individual treatment and prognostic estimations.

Efficacy of Monsel Solution After Cervical Biopsy: A Randomized Trial.

OBJECTIVES: To estimate the efficacy and side effects of Monsel solution for hemostasis after cervical punch biopsy. METHODS: In a prospective, randomized trial, we compared application of Monsel solution versus a "wait and see" approach in women undergoing cervical punch biopsies in a 1:1 ratio. The primary end point was vaginal bleeding (VB) after 15 minutes measured by scoring a sanitary pad with a 5-level pictogram. Secondary end points were VB after 3, 6, and 24 hours (5-level pictogram), subjective estimation of overall VB during 24 hours, pain after 15 minutes and subjective estimation of overall pain after 24 hours, and overall satisfaction after 24 hours (11-level visual analogue scale). RESULTS: One hundred forty-five women were randomized between July 2015 and January 2016. Mean objective VB scores after 15 minutes in 75 women with Monsel solution were 1.2 ± 0.6 compared with 1.8 ± 1.0 in 70 women without Monsel solution (P < 0.001). The secondary end points VB after 3 and 6 hours, but not after 24 hours, were also in favor of Monsel solution (2.1 ± 1.1 vs 2.9 ± 1.2; P < 0.001; 1.6 ± 0.7 vs 2.2 ± 1.0; P < 0.001; 1.6 ± 0.9 vs 1.7 ± 0.9; P = 0.4, respectively). Subjective estimation of overall VB during 24 hours was lower for Monsel solution (23.2 ± 15.8 vs 35.9 ± 19.5; P < 0.001), but pain after 15 minutes, overall pain, and overall satisfaction were not significantly different between groups (19.2 ± 14.4 vs 17.9 ± 16.2; P = 0.3; 20.7 ± 15.8 vs 20.1 ± 18.0; P = 0.5; and 44.1 ± 21.5 vs 43.6 ± 23.2; P = 0.9, respectively). CONCLUSIONS: Application of Monsel solution significantly reduces bleeding for 6 hours after cervical biopsy but does not affect overall pain or overall satisfaction.

Spray Versus Forced Coagulation in Large Loop Excision of the Transformation Zone: A Randomized Trial.

OBJECTIVE: Large loop excision of the transformation zone (LLETZ) is the standard surgical treatment for cervical dysplasia. The optimal way to achieve local hemostasis in women undergoing LLETZ is unknown. MATERIALS AND METHODS: In a prospective, randomized trial, we compared spray coagulation and forced coagulation in women undergoing LLETZ in a 1:1 ratio. The primary endpoint was time to complete local hemostasis (TCLH). Secondary endpoints were blood loss (Δ hemoglobin before and after LLETZ), pain (numerical visual analog scale, 5-step graphical visual analog scale measured 2-3 hours after LLETZ), and perioperative/postoperative complications (intraoperative need for sutures, postoperative bleeding, infection, and unscheduled readmission). Analysis was by intention to treat. RESULTS: One hundred fifty-one women were enrolled and were eligible for analysis. Mean (SD) TCLH in 80 women with forced coagulation was 43.3 (38.5) and 28.9 (22.9) seconds in 71 women with spray coagulation (p < 0.001). The secondary endpoints blood loss (Δ hemoglobin, -0.8 [0.8] vs -0.7 [1.1]; p = 0.115), pain (numerical visual analog scale, 4.1 [0.9] vs 4.2 [0.9]; p = 0.283, graphical visual analog scale (1.9 [1.3] vs 1.8 [1.3]; p = 0.888), and perioperative/postoperative complications (6/71 [8%] vs 7/80 [9%]; p = 0.822) were comparable between the 2 arms. In a multivariate analysis, coagulation method (odds ratio = 0.18; 95% CI = 0.09-0.38; p < 0.001) and size of the cervix (odds ratio = 2.43; 95% CI = 1.16-5.15; p = 0.021) were independent predictors of TCLH. CONCLUSIONS: Spray coagulation is superior to forced coagulation in women undergoing LLETZ and should be used as the standard approach.

Hyperthermic intraperitoneal chemotherapy for women with granulosa cell tumors of the ovary: a systematic review of the literature.

Background: Adult and juvenile granulosa cell tumors of the ovary are rare functional sex-cord-stromal ovarian neoplasms characterized by low malignant potential and late relapse. Evidence-based management options for primary and recurrent juvenile (JGCT) and adult (AGCT) granulosa cell tumors are limited and treatment options have not been standardized. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be an option to treat these women effectively. Methods: Systematic literature review using PubMed and the Cochrane Central Register of Controlled Trials. Results: No reports of HIPEC among women with a first diagnosis of AGCT were identified. We identified 5 reports on the safety and therapeutic efficacy of CRS and HIPEC in 19 patients with recurrent AGCT and one patient with JGCT. The pooled rate of complete cytoreduction was 95 % (18/19) with 16 % (3/19) severe morbidity and no procedure-related mortality. The median time of follow-up was 30 (range, 3 to 72) months, during which 6/19 (31 %) patients experienced a recurrence and two patients (10 %) died of the disease. Conclusion: CRS and HIPEC are a safe and potentially effective treatment option for selected women with recurrent AGCT limited to the abdomen.

Quality of websites of obstetrics and gynecology departments: a cross-sectional study.

BACKGROUND: The internet has become an easily accessible and widely used source of healthcare information. There are, however, no standardized or commonly accepted criteria for the quality of Obstetrics and Gynecology websites. In this study, we aimed to evaluate the quality of websites of Obstetrics and Gynecology departments in German-speaking countries and to compare websites nationally and internationally. METHODS: We scored 672 websites from Germany (n = 566), Austria (n = 57), and Switzerland (n = 49) using the objective criteria: Google search rank (2 items), technical aspects (11 items), navigation (8 items), and content (6 items) for a 26 point score. Scores were compared nationally and internationally. Multivariable regression models assessed good quality scores (≥50% of maximum) as the dependent variables and country, academic affiliation, being member of a healthcare consortium, confessional affiliation, and content management system (CMS) use as independent variables. RESULTS: The mean score of websites was 13.8 ± 3.3. 4.2% were rated as good (≥75% of maximum), 61.8% as fair (≥50% of maximum). German (14.0 ± 3.2) and Swiss (13.8 ± 4.0) websites scored significantly higher compared to Austrian websites (11.6 ± 2.5) (P < 0.001 and P = 0.005, respectively). Within Germany, academic had higher scores than non-academic departments (14.9 ± 3.2 vs. 13.7 ± 3.1, P < 0.001). Single institutions had higher scores compared to healthcare consortium institutions (14.1 ± 3.2 vs. 13.2 ± 2.6, P = 0.003). Departments in Northern and Southern states had higher scores compared to Eastern states (14.4 ± 3.2 and 14.2 ± 3.2 vs. 13.0 ± 3.0, P < 0.001). In multivariate regression models, all subscores (all: P < 0.001) independently predicted a website's reaching a good quality score, with navigation subscore as strongest predictor. Affiliations were predictors for some good individual subscores, but not for others. High content subscore was associated with good Google search rank, technical aspects, and navigation subscores. CONCLUSIONS: The quality of websites of Obstetrics and Gynecology departments varies widely. We found marked differences depending on country, affiliation, and region.

Decline of semen quality during IVF is not associated with subjective male stress.

The aim of the present study was to assess if semen quality declines during in vitro fertilization (IVF) and whether or not this phenomenon is triggered by chronic male stress. In order to test this hypothesis, we first investigated a retrospective cohort of 155 male IVF patients (testing cohort). Subsequently, we started a prospective cohort study in men undergoing their first IVF and assessed semen quality and subjective male chronic stress using a validated tool, i.e. the Fertility Problem Inventory (FPI) questionnaire. The association between stress and sperm quality decline measured 4-6 weeks before the start of IVF (T1) and at the day of oocyte retrieval (T2) was the primary outcome. Live birth rate, first trimester abortion and rate of poor responders were secondary outcomes. In the testing cohort, mean progressive motility, but not mean sperm density significantly declined. There were 78/154 (51%) men who showed a decline in semen density and 50/154 (32%) men who showed a decline in progressive motility. In the validation cohort, progressive motility declined, whereas, sperm density increased from T1 to T2. Of 78 men, 27 men had increased stress (FPI-score > 146). Sperm density and progressive motility were not significantly different in men with and without stress. However, in the presence of male stress, couples had a higher rate of poor responders, miscarriages and a lower rate of live births. Subjective stress is not associated with a decline in semen quality observed during IVF but may be associated with adverse pregnancy outcome.

Objective Structured Assessment of Technical Skills (OSATS) evaluation of theoretical versus hands-on training of vaginal breech delivery management: a randomized trial.

OBJECTIVE: To compare the skills of performing a vaginal breech (VB) delivery after hands-on training versus demonstration. STUDY DESIGN: We randomized medical students to a 30-min demonstration (group 1) or a 30-min hands-on (group 2) training session using a standardized VB management algorithm on a pelvic training model. Subjects were tested with a 25 item Objective Structured Assessment of Technical Skills (OSATS) scoring system immediately after training and 72 h thereafter. OSATS scores were the primary outcome. Performance time (PT), self assessment (SA), confidence (CON), and global rating scale (GRS) were the secondary outcomes. Statistics were performed using the Mann-Whitney U-test, chi-square test, and multiple linear regression analysis. RESULTS: 172 subjects were randomized. OSATS scores (primary outcome) were significantly higher in group 2 (n=88) compared to group 1 (n=84) (21.18±2.29 vs. 20.19±2.37, respectively; p=0.006). The secondary outcomes GRS (10.31±2.28 vs. 9.17±2.21; p=0.001), PT (214.60±57.97 s vs. 246.98±59.34 s; p<0.0001), and CON (3.14±0.89 vs. 2.85±0.90; p=0.04) were also significantly different between groups, favoring group 2. After 72 h, primary and secondary outcomes were not significantly different between groups. In a multiple linear regression analysis, group assignment (odds ratio [OR] 1.60; 95% confidence interval [CI] 1.14-2.05; p<0.0001) and gender (OR 2.91; 95% CI 2.45-3.38; p<0.0001) independently influenced OSATS scores. CONCLUSION: Hands-on training leads to a significant improvement of VB management in a pelvic training model, but this effect was only seen in the short term.

Objective structured assessment of technical skills evaluation of theoretical compared with hands-on training of shoulder dystocia management: a randomized controlled trial.

OBJECTIVE: To compare the skills of performing a shoulder dystocia management algorithm after hands-on training compared with demonstration. METHODS: We randomized medical students to a 30-minute hands-on (group 1) and a 30-minute demonstration (group 2) training session teaching a standardized shoulder dystocia management scheme on a pelvic training model. Participants were tested with a 22-item Objective Structured Assessment of Technical Skills scoring system after training and 72 hours thereafter. Objective Structured Assessment of Technical Skills scores were the primary outcome. Performance time, self-assessment, confidence, and global rating scale were the secondary outcomes. Statistics were performed using Mann-Whitney U test, χ test, and multiple linear regression analysis. RESULTS: Two hundred three participants were randomized. Objective Structured Assessment of Technical Skills scores were significantly higher in group 1 (n=103) compared with group 2 (n=100) (17.95±3.14 compared with 15.67±3.18, respectively; P<.001). The secondary outcomes global rating scale (GRS; 10.94±2.71 compared with 8.57±2.61, respectively; P<.001), self-assessment (3.15±0.94 compared with 2.72±1.01; P=.002), and confidence (3.72±0.98 compared with 3.34±0.90, respectively; P=.005), but not performance time (3:19±0:48 minutes compared with 3:31±1:05 minutes; P=.1), were also significantly different, favoring group 1. After 72 hours, Objective Structured Assessment of Technical Skills scores were still significantly higher in group 1 (n=67) compared with group 2 (n=60) (18.17±2.76 compared with 14.98±3.03, respectively; P<.001) as were GRS (10.80±2.62 compared with 8.15±2.59; P<.001) and self assessment (SA; 3.44±0.87 compared with 2.95±0.94; P=.003). In a multiple linear regression analysis, group assignment (group 1 compared with 2; P<.001) and sex (P=.002) independently influenced Objective Structured Assessment of Technical Skills scores. CONCLUSION: Hands-on training helps to achieve a significant improvement of shoulder dystocia management on a pelvic training model. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01618565. LEVEL OF EVIDENCE: I.

Two multidrug-resistance (ABCB1) gene polymorphisms as prognostic parameters in women with ovarian cancer.

BACKGROUND: The transport protein P-glycoprotein, which is encoded by the multidrug-resistance ABCB1 gene, is crucially involved in the export of taxanes and other cytotoxic substances out of the cell. Treatment response to paclitaxel has been shown to correlate with ABCB1 gene polymorphisms. Data regarding the prognostic value of ABCB1 gene polymorphisms in ovarian cancer patients is conflicting. MATERIALS AND METHODS: The present study evaluates the association of two common ABCB1 gene polymorphisms, namely G2677T/A in exon 21 (rs2032582) and C3435T in exon 26 (rs1045642), and survival in 106 Caucasian women with ovarian cancer. RESULTS: The two ABCB1 gene polymorphisms (G2677T/A and C3435T) were associated neither with disease-free (p=0.8 and p=0.9, respectively) nor with overall survival (p=0.9 and p=0.9, respectively). Tumor stage (p=0.01; p=0.01) and residual tumor mass (p=0.005; p=0.01), but not tumor grade and age at diagnosis were associated with disease-free and overall survival, respectively, in a multivariate analysis. Haplotype analysis did not reveal any association between the combined effect of the two gene polymorphisms and survival. CONCLUSION: In the present study, ABCB1 G2677T/A and ABCB1 C3435T gene polymorphisms were not found to be associated with prognosis in Caucasian women with ovarian cancer.

Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals.

OBJECTIVE: To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). DESIGN: Prospective cohort study. SETTING: Academic research institution. PATIENT(S): Five hormone-naïve FtM transsexuals before and after HT. INTERVENTION(S): Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. MAIN OUTCOME MEASURE(S): Differential regulation of specific genes and gene expression signatures. RESULT(S): We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer-associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. CONCLUSION(S): Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer-related gene expression signatures.

OCT-4 expression in follicular and luteal phase endometrium: a pilot study.

BACKGROUND: The stem cell marker Octamer-4 (OCT-4) is expressed in human endometrium. Menstrual cycle-dependency of OCT-4 expression has not been investigated to date. METHODS: In a prospective, single center cohort study of 98 women undergoing hysteroscopy during the follicular (n = 49) and the luteal (n = 40) phases of the menstrual cycle, we obtained endometrial samples. Specimens were investigated for OCT-4 expression on the mRNA and protein levels using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Expression of OCT-4 was correlated to menstrual cycle phase. RESULTS: Of 89 women sampled, 49 were in the follicular phase and 40 were in the luteal phase. OCT-4 mRNA was detected in all samples. Increased OCT-4 mRNA levels in the follicular and luteal phases was found in 35/49 (71%) and 27/40 (68%) of women, respectively (p = 0.9). Increased expression of OCT-4 protein was identified in 56/89 (63%) samples. Increased expression of OCT-4 protein in the follicular and luteal phases was found in 33/49 (67%) and 23/40 (58%) of women, respectively (p = 0.5). CONCLUSIONS: On the mRNA and protein levels, OCT-4 is not differentially expressed during the menstrual cycle. Endometrial OCT-4 is not involved in or modulated by hormone-induced cyclical changes of the endometrium.

Repeat surgery in patients with cervical cancer stage FIGO IA1: a series of 156 cases and a review of the literature.

BACKGROUND: Many physicians advocate repeat surgery after cervical conization with a diagnosis of cervical cancer stage FIGO IA1. In a multicenter trial, whether repeat surgery is a necessary therapeutic procedure in the treatment of cervical cancer stage FIGO IA1 was evaluated and a literature review performed. PATIENTS AND METHODS: From 1997 to 2006, 156 patients with squamous cell cervical cancer, stage FIGO IA1, were primarily treated with conization in three different institutions; 102 of these patients underwent repeat surgery, comprising the study group for the present trial. RESULTS: In the conization specimen, 22 patients had clear resection margins, none of whom had residual dysplasia in the repeat conization/hysterectomy specimen. Sixty-four patients had cervical intraepithelial neoplasia (CIN) I-III at the conization resection margin; of these, 29, 9, 24, and 2 patients had no sign of residual dysplasia, CIN I, CIN II/III, or multifocal cervical cancer FIGO IA1 in the repeat conization/hysterectomy specimen, respectively. Sixteen patients had invasive cancer at the resection margin of the conization specimen; no sign of dysplasia, CIN I, CIN II/III, or residual cervical cancer were found in the repeat conization/hysterectomy specimen in 4, 1, 5, and 6 cases, respectively. In a multivariate analysis, risk factors for residual CIN II/III or multifocal invasive carcinoma in patients with CIN at the resection margin were advanced patient age and presence of multifocal invasive cervical cancer, but not depth of invasion, lymphovascular space involvement (LVSI), nor positive endocervical curettage. CONCLUSION: The risk of residual dysplasia after conization of FIGO IA1 cervical cancer with clear margins is minimal. A considerable number of patients with locally resected FIGO IA1 cervical cancer, who had CIN I-III at the resection margin, showed signs of residual high-grade CIN or multifocal cervical cancer. The need for repeat surgery when signs of invasive carcinoma are present at the resection margins after conization is clear.

Side effects of phytoestrogens: a meta-analysis of randomized trials.

BACKGROUND: Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown. METHODS: Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials. RESULTS: We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively (P=.2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=.003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups. CONCLUSIONS: Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.

Serum C-reactive protein in the differential diagnosis of ovarian masses.

OBJECTIVE: A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer. STUDY DESIGN: In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n=44, epithelial ovarian cancer [EOC]: n=198) ovarian masses. Results were correlated to clinical data. RESULTS: Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6)mg/dL, 0.5 (0.5, 0.9)mg/dL, and 1.36 (0.5, 4.9)mg/dL, respectively (p<0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p<0.001), residual tumor mass (p<0.001), and patients' age (p=0.04), but not with tumor grade (p=0.2) and histologic type (p=0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients' age, serum CRP independently predicted the presence of malignant ovarian masses (p<0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8-7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively. CONCLUSION: Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients' age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.

Intrauterine fetal death and delivery complications associated with coagulopathy: a retrospective analysis of 104 cases.

OBJECTIVE: To assess the prevalence of delivery complications associated with coagulopathy in women with intrauterine fetal death (IUFD). METHODS: This is a retrospective cohort study of women with IUFD at >24 weeks gestation or a birth weight of >500 g between 1994 and 2007. Clinical data were assessed by chart review. RESULTS: One hundred four women were diagnosed with IUFD. The mean time between diagnosis of IUFD and delivery was 28.8 (+/-17.4) hours. Twelve of 104 (11.5%) women had a delivery complication associated with coagulopathy, defined as need for blood transfusion. In 8 of these 12 women, coagulopathy was associated with a preexisting preeclampsia/hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, uterine rupture after induction, or an acute clinical problem at presentation to the clinic. In 4 of 104 (4%) women, there was no attributable cause of coagulopathy other than IUFD. In these women, there was a statistically significant difference of laboratory parameters of coagulation at the time of diagnosis of IUFD compared with women who did not subsequently develop coagulopathy; platelet count 93.3 +/- 96.4 vs. 229.3 +/- 68.1 G/L, p < 0.001; prothrombin time (PT) 97.0 +/- 43.9 vs. 123.3 +/- 21.1 %, p = 0.02; activated partial thromboplastin time (aPTT) 42.9 +/- 34.0 vs. 31.5 +/- 4.3 sec, p = 0.01; thrombin time (TT) 22.8 +/- 16.5 vs. 14.1 +/- 13.3 sec, p = 0.02), plasma fibrinogen 219.0 +/- 117.5 vs. 472.9 +/- 122.8 mg/dL, p < 0.001), and antithrombin III 70.5 +/- 21.9 vs. 101.5 +/- 17.0 %, p = 0.01. CONCLUSIONS: Delivery complications associated with coagulopathy occur in 11% of women with IUFD and are associated with preexisting preeclampsia/HELLP, uterine rupture, or an acute clinical problem in most cases. In 4% of women with IUFD, coagulopathy develops without an apparent cause.

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients.

OBJECTIVE: To systematically monitor the frequency and risk factors of adverse events (AEs) in a reproductive surgery endoscopy unit. DESIGN: Prospective cohort study. SETTING: Academic research institution. PATIENT(S): All consecutive surgical patients of a reproductive surgery unit from December 2005 to March 2007. INTERVENTION(S): Monitoring for predefined AEs by trained observers. MAIN OUTCOME MEASURE(S): Number of preventable and not preventable AEs, medical errors, and system problems. Univariate analysis and multivariate logistic regression were used to identify risk factors of AEs. RESULT(S): Seven hundred ninety-six women were included. We identified 60 AEs in 45 patients (risk 6%; 95% confidence interval [CI] 1%-11%). Adverse events were postoperative fever (n = 1), wound breakdown (n = 1), intraoperative or postoperative administration of packed erythrocytes (n = 6), surgical revision (n = 7), unplanned readmission (n = 5), transfer to intensive care unit (n = 1), conversion (n = 8), intraoperative organ injury (n = 9), blood loss >500 mL (n = 3), surgery canceled (n = 15), and other AEs (n = 4). Six patients (risk 0.8%; 95% CI 0-2%) had multiple AEs. One (0.01%) and 11 (1.4%) AEs were deemed due to medical errors and system problems, respectively. Twelve and 48 AEs were deemed preventable and not preventable, respectively. In a univariate and multivariate analysis, only duration of surgery (odds ratio 3.78; 95% CI 1.95-7.33) was significantly associated with having an AE. CONCLUSION(S): Clinical outcome monitoring is a useful tool for assessing the outcome quality of reproductive surgery by identifying potentially preventable AEs and associated risk factors.

Endocervical cytobrush for the detection of cervical dysplasia before large loop excision of the transformation zone (LLETZ).

BACKGROUND: We aimed to identify the number of histologically verified cervical intraepithelial neoplasia (CIN)/cervical cancer lesions detected by endocervical cytobrush (EC) which have been missed by repeat PAP smear and colposcopy before large loop excision of the transformation zone (LLETZ). PATIENTS AND METHODS: A retrospective cohort study of 1,676 consecutive patients in a colposcopy clinic undergoing repeat PAP smear, colposcopy, biopsy, and subsequent LLETZ. RESULTS: Data were available for 1,421 patients. EC identified 31/1,367 (2.2%) cases of CIN and/or cervical cancer missed by repeat PAP smear and colposcopy. Compared to repeat PAP smear and colposcopy, the combination of repeat PAP smear, colposcopy and EC increased the positive predictive value (PPV) (89.6% vs. 98.9%, p=0.07), but this difference was not statistically significant. Sensitivity (93.1% vs. 93.9%; p=0.8), specificity (27.7% vs. 27.7%; p=1.0), and negative predictive value (NPV) (11.9% vs. 13.1%, p=0.9) were also not significantly different. The number needed to screen (NNS) for identifying one additional case of CIN and/or invasive cancer by EC was 45. In a multivariate analysis, presence of CIN/cervical cancer in the LLETZ specimen and human papilloma virus infection, but not age, visibility of the transformation zone or presence of an endovcervical lesion were independently associated with the likelihood of CIN and/or invasive cancer detected by EC. CONCLUSION: Adding EC to repeat PAP smear and colposcopy identifies 2.2% more cases of CIN and/or cervical cancer, but does not significantly increase the sensitivity, specificity, PPV or NPV of repeat PAP smear and colposcopy.