Risk of endometrial cancer in asymptomatic postmenopausal patients with thickened endometrium: data from the FAME-Endo study: an observational register study.

PURPOSE: To evaluate the risk for endometrial cancer (EC) in a large series of asymptomatic patients with thickened endometrium at ultrasound examination based on previously published data of a theoretical cohort. METHODS: In a prospective register study, a total of 1024 women with thickened endometrium in ultrasound examination undergoing histological diagnosis by dilation, hysteroscopy and curettage were evaluated. 124 patients were excluded due to current medication with tamoxifen and/or presence of HNPCC leaving 900 patients for further analysis. RESULTS: Mean [standard deviation (SD)] age of patients was 65.6 (8.6) years. Mean (SD) endometrial thickness was 11.9 (5.8) mm. 32 and 6 cases of EC and complex endometrial hyperplasia with atypia were found, respectively. In the univariate analysis, a statistically significant association between endometrial thickness, current use of antihypertensive medication, number of deliveries, and the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05) with EC was found. A multivariate logistic regression model incorporating these parameters showed a statistically significant independent association of endometrial thickness, number of deliveries, and the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05), but not current use of antihypertensive medication, with EC. Using a cut-off of the endometrial thickness of > 11 mm, the risk for "EC alone" and "EC and complex endometrial hyperplasia with atypia combined" was found to be 6.7% and 7.9%, respectively. CONCLUSIONS: Our data compare favorably to a theoretical cohort suggesting a clinically reasonable cut-off of > 11 mm endometrial thickness to discriminate between "normal" and "pathological". The data regarding "risk for endometrial cancer" can be used for counseling affected women.

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.

One-stop clinical assessment of risk for endometrial hyperplasia (OSCAR-Endo): a fast-track protocol for evaluating endometrial pathologies.

PURPOSE: To evaluate a one-stop clinical assessment of risk for assessing endometrial pathologies (OSCAR-Endo), consisting of a fast-track protocol with hysteroscopy, dilation and curettage (D&C) with intraoperative frozen section analysis of the removed tissue in cases of hysteroscopic suspicion of malignancy. METHODS: In this prospective clinical trial, a total of 304 consecutive women with sonographically suspected endometrial hyperplasia and/or postmenopausal bleeding, underwent D&C with intraoperative frozen section analysis between May 2013 and September 2015. Based on the results of the hysteroscopy and/or frozen section, the OSCAR-Endo score was reported: negative, when no frozen section was regarded necessary or the frozen section yielded a negative result; equivocal, when the frozen section reported an equivocal result; positive, when frozen section reported either complex hyperplasia with atypia or cancer. RESULTS: Frozen sections were required by the surgeons in 59 (19.4%) of cases. When compared with the final histology after D&C, frozen section showed a sensitivity, specificity, PPV, NPV, and overall test accuracy of 91.3, 100, 100, 94.1, and 96.3% for predicting malignant disease, respectively. The OSCAR-Endo score showed a sensitivity, specificity, PPV, NPV, and overall test accuracy of 84, 100, 100, 98.6, and 98.7% for predicting malignant disease, respectively. CONCLUSION: The OSCAR-Endo protocol is easy to perform in daily clinical practice reaching an excellent test accuracy. It helps in immediate postoperative counseling of affected patients. Clinical Trial Registration http://www.clinicaltrials.gov ; NCT01961102.

Compartment syndrome after gynecologic laparoscopy: systematic review of the literature and establishment of normal values for postoperative serum creatine kinase and myoglobin levels.

PURPOSE: To evaluate published evidence in the literature on compartment syndrome (CS) in association with gynecologic surgery and to establish postoperative normal values for serum creatine kinase (CK) and myoglobin. METHODS: The present study consists of a case report of a patient with CS, a systematic review including 37 studies and 86 patients with CS, and a retrospective cohort study of 300 patients undergoing various types of laparoscopy for benign or malignant diseases in order to establish postoperative normal values. RESULTS: We report on a patient with early-stage ovarian cancer, who developed CS after laparoscopic surgery with massively elevated serum CK and myoglobin levels, i.e., 1109 U/L and 18151 µg/L, respectively. In our systematic review, median serum CK and myoglobin levels among women with CS were 19,223 (177-27,412) U/L and 1248 (285-1360) µg/L, respectively. In our cohort study, the median postoperative serum CK and myoglobin levels were 68 (14-1576) U/L and 45 (14-1040) µg/L, respectively. The 95th and 99th percentile of serum CK and myoglobin levels were 158 and 391.5 U/L, and 152.3 and 298.9 µg/L, respectively. CONCLUSION: Markedly elevated postoperative serum levels of CK and myoglobin levels might raise the suspicion for CS and could therefore aid in the rapid diagnosis of CS.

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.

Association of -463G/A MPO gene polymorphism and risk of cervical intraepithelial neoplasia.

PURPOSE: The MPO system plays an important role in the control of infections and the deletion of malignant cells. Nevertheless, alternations in the MPO system can lead to DNA damage and carcinogenesis. Polymorphisms in the MPO Gene have been associated with an increased expression of MPO and a higher risk for development of cancer. This study evaluates the association between -463G/A MPO gene polymorphism and the risk for CIN. METHODS: The MPO gene polymorphism (-463G/A) was investigated in 616 women with cervical intraepithelial neoplasia and in 206 healthy women. Association between MPO gene polymorphism and risk of cervical intraepithelial neoplasia were analyzed by univariate and multivariable models. RESULTS: No significant difference in genotype distribution of the MPO gene polymorphism was observed in women with CIN and controls (p = 0.4; OR 1.2, 95 % CI 0.8-1.6). A subgroup analysis only including women with CIN did not show an association between -463G/A MPO gene polymorphism and risk for high-grade CIN (CIN 2/3) (p = 0.09; OR 1.5, 95 % CI 0.9-2.3). CONCLUSIONS: The investigated MPO gene polymorphism is not associated with risk for the development of cervical intraepithelial neoplasia.

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.

Plasma fibrinogen levels in patients with benign and malignant ovarian tumors.

OBJECTIVE: Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors. METHODS: In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association. RESULTS: Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (p<0.001). Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels (485.5 [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL; p=0.03). In a multivariate model plasma fibrinogen was identified to be independently associated with the presence of BOT and EOC. In the subgroup of patients <50 years, plasma fibrinogen levels remained independently associated with malignant ovarian tumors in CA 125 positive and negative patients. CONCLUSION: Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in the subgroup of patients <50 years, in whom differential diagnosis of ovarian tumors is particularly challenging.

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.

Prophylactic long-acting granulocyte-colony stimulating factors (G-CSF) in gynecologic malignancies: an oncologic expert statement.

We reviewed the status of the use of the prophylactic long-acting granulocyte colony-stimulating factors (G-CSFs) pegfilgrastim and lipegfilgrastim in gynecologic malignancies. Long-acting G-CSFs should not be used in weekly regimens. Filgrastim is not indicated in patients with febrile and/or severe neutropenia after administration of long-acting G-CSF in the same cycle. One study has shown a moderate effect on febrile neutropenia of ciprofloxacin when co-administered with pegfilgrastim. There is broad evidence from meta-analyses that pegfilgrastim effectively reduces severe neutropenia. In parallel, its adverse effects have been studied extensively. All-cause mortality was significantly reduced by pegfilgrastim. The glycopegylated long-acting G-CSF, lipegfilgrastim has demonstrated antineutropenic efficacy similar to that of pegfilgrastimin in one breast cancer study. In another pivitol non-small cell lung cancer study, impaired survival was observed in the lipegfilgrastim group during the first 30 days of study. The European Medicines Agency claimed more profound safety data to be provided for lipegfilgrastim by 2017.

A novel training model for the loop electrosurgical excision procedure: an innovative replica helped workshop participants improve their LEEP.

We wanted to evaluate the feasibility and effect of a hands-on loop electrosurgical excision procedure (LEEP) 2.5-day intensive surgical skills workshop, using a novel training model on porcine tissue. Hands-on simulation-based training was conducted to emphasize colposcopy, local anesthesia, uterine cervix and vulva punch biopsy, LEEP, and complication management. Performance of 51 participants' technical skills was assessed before and after training completion. LEEP performance was significantly better after completion of the training (P < .001). Before and after training mean scores (SD) of 18.0 (3.5) and 23.4 (2.1) were assessed. Multivariate analysis revealed that the training effects were independent of previous surgical expertise. The LEEP workshop was feasible and effective and we recommend implementing hands-on LEEP training into gynecology training programs.

Neonatal simulation training decreases the incidence of chest compressions in term newborns.

AIM OF THE STUDY: To determine the effectiveness of a multidimensional neonatal simulation-based medical education training programme on direct and indirect patient outcome parameters. METHODS: This was a retrospective analytical study with a historical control group in a level II neonatal care unit (1,700 births per year). A multidimensional interdisciplinary training programme on neonatal resuscitation was implemented in 2015; pre-training (2012-2014) and post-training (2015-2019) eras were compared in terms of mortality (direct outcome) and the received intervention level immediately after birth (indirect outcome). Intervention levels were defined as follows: A) short-term non-invasive ventilation, B) prolonged non-invasive ventilation (>5 inflation breaths), C) chest compressions. RESULTS: Of 13,950 neonates born during the study period, 826 full-term newborns received one of the three intervention levels for adaptation after birth. A total of 284 (34.4%) patients received short-term non-invasive ventilation (A), 477 (57.8%) had prolonged ventilation (B), and 65 (7.9%) chest compressions (C), respectively. Comparing the pre- and post-training eras, there was no significant reduction in mortality, and no significant changes were found in groups A or B. However, the risk for chest compressions (group C) decreased significantly from 0.91% in the pre-training era to 0.20% in the post-training era (p < 0.001). CONCLUSION: Although there was no significant effect on neonatal mortality, regular interdisciplinary simulation training decreased the number of administered chest compressions immediately after birth. Further studies are needed to test indirect outcome-related parameters, such as frequency of chest compressions as a measure of effectiveness and impact of medical training.

TRICIN: A Phase II Trial on the Efficacy of Topical TRIchloroacetic Acid in Patients with Cervical Intraepithelial Neoplasia.

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN.

Genetic variations of interleukin-1 and -6 genes and risk of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the association between five interleukin-1 (IL-1) and -6 gene polymorphisms and risk of high grade cervical intraepithelial neoplasia (CIN 2-3). METHODS: This case-control study investigates five common IL-1 and IL-6 gene polymorphisms in 131 women with CIN 2-3 and 209 controls by pyrosequencing and polymerase chain reaction. Associations between gene polymorphisms and risk of CIN 2-3 are analysed by univariate and multivariable models. Their combined effect on the risk of CIN is evaluated by haplotype analysis. RESULTS: In a multivariable regression model IL1A -889 (odds ratio 0.3 [95% confidence interval 0.1-0.8], p=0.01) and smoking (4.0 [1.7-9.1], p=0.001) are independently associated with the risk of high grade CIN. Haplotype analysis does not reveal any high-risk combinations for the susceptibility of CIN. CONCLUSION: The single nucleotide polymorphism IL1A -889 is independently associated with risk of high grade CIN.

Expression of epidermal growth factor receptor and vascular endothelial growth factor in vaginal squamous cell cancer.

OBJECTIVE: Primary invasive squamous cell carcinoma of the vagina is a rare neoplasm. Investigations concerning the potential of new therapeutic targets are limited. STUDY DESIGN: A total of 34 patients with primary invasive squamous cell carcinoma of the vagina was identified, who were treated at our institution between 1994 and 2008. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression was assessed using immunohistochemistry from paraffin-embedded tissue blocks. RESULTS: EGFR was expressed in 33 of 34 (97.1%) and VEGF was expressed in 12 of 34 cases (35.3%). There was no statistically significant relationship between clinicopathologic parameters (clinical stage, grading, tumor size), patient survival, and EGFR and VEGF expression. CONCLUSION: VEGF was moderate and EGFR was frequently expressed in invasive squamous cell carcinoma of the vagina. In our sample size, immunohistochemical staining was not statistically significantly associated with prognosis.

The prognostic role of human papillomavirus in patients with vaginal cancer.

OBJECTIVE: The objective of the study was to evaluate the association between human papillomavirus (HPV) infection and clinical-pathological parameters in primary squamous cell carcinoma of the vagina and assess the value of HPV infection as a prognostic parameter. METHODS: In our retrospective study, we identified 37 consecutive patients with primary invasive squamous cell carcinoma of the vagina; 35 patients were eligible for further investigations. Human papillomavirus detection was assessed by in situ hybridization assays from paraffin-embedded tissue blocks. Human papillomavirus detection was correlated with clinical-pathological parameters by χ² and Fisher exact tests. Univariate log-rank tests and multivariate Cox regression models were used to evaluate the association between HPV infection and patient survival. RESULTS: Human papillomavirus DNA was detected in 18 (51.4%) of 35 cases. Human papillomavirus status did no influence clinical-pathological parameters, such as clinical stage (P=0.9), grade (P=0.9), and tumor size (P=0.18). Prognosis did not significantly differ between HPV-positive and HPV-negative tumors in the entire cohort; however, patients with unfavorable tumor stage (International Federation of Gynecology and Obstetrics stage≥III) and HPV positivity had improved disease-free (P=0.004) and overall survival (P=0.023). CONCLUSIONS: Human papillomavirus infection was frequently detected in squamous cell carcinoma of the vagina, and its presence may serve as a prognostic indicator in advanced stages.

Vascular endothelial growth factor gene polymorphisms and risk of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the association between 3 vascular endothelial growth factor (VEGF) gene polymorphisms and susceptibility of cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: This prospectively collected case-control study investigates three common VEGF gene polymorphisms (ie, VEGF -460 [rs833061], VEGF +405 [rs2010963], and VEGF +936 [rs3025039]) in 203 women with CIN and 209 healthy women by DNA pyrosequencing. Associations between polymorphisms and CIN risk are evaluated with univariate and multivariable models and haplotype analysis. RESULTS: In a multivariable regression model, the variant VEGF +405C allele was associated (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.1], P = 0.02) with increased susceptibility of CIN independent of number of sexual partners (OR, 2.2; 95% CI, 1.1-4.6; P = 0.03) and smoking (OR, 3.3; 95% CI, 1.6-6.6; P = 0.001). The haplotype VEGF -460C - +405C - +936C was associated with an OR of 5.2 (95% CI, 1.2-52.7) for the susceptibility of CIN. CONCLUSIONS: The presence of the variant VEGF +405C allele and the haplotype VEGF -460C - +405C - +936C are independently associated with higher susceptibility of CIN.

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.

The inflammation-based Glasgow Prognostic Score predicts survival in patients with cervical cancer.

OBJECTIVES: The Glasgow Prognostic Score (GPS) is known to reflect the degree of tumor-associated cachexia and inflammation and is associated with survival in various malignancies. We investigated the value of the GPS in patients with cervical cancer. METHODS: We included 244 consecutive patients with cervical cancer in our study. The pretherapeutic GPS was calculated as follows: patients with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, and patients with 1 or no abnormal value were allocated a score of 1 or 0, respectively. The association between GPS and survival was evaluated by univariate log-rank tests and multivariate Cox regression models. The GPS was correlated with clinicopathologic parameters as shown by performing chi2 tests. RESULTS: In univariate analyses, GPS (P < 0.001, P < 0.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001, P < 0.001), and lymph node involvement (P < 0.001, P < 0.001), but not patients' age (P = 0.2, P = 0.07), histological grade (P = 0.08, P = 0.1), and histological type (P = 0.8, P = 0.9), were associated with disease-free and overall survival, respectively. In a multivariate analysis GPS (P = 0.03, P = 0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003, P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P = 0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with disease-free and overall survival, respectively. The GPS was associated with FIGO stage (P < 0.001) and histological grade (P = 0.02). CONCLUSIONS: The GPS can be used as an inflammation-based predictor for survival in patients with cervical cancer.