Christer Borgfeldt

Menopause-related symptoms: what are the background factors? A prospective population-based cohort study of Swedish women (The Women's Health in Lund Area study).

OBJECTIVE The purpose of this study was to analyze the influence of sociodemographic characteristics and environmental factors on self-reported menopause-related symptoms among middle-aged Swedish women. STUDY DESIGN Women who were born in the years 1935 to 1945 and who were living in the Lund area of southern Sweden were investigated. Each woman completed a generic questionnaire and underwent a personal interview that pertained to sociodemographic characteristics, lifestyle, and current health-related problems. With these background factors, the frequency and intensity of hot flushes and vaginal dryness were determined; risk factor analysis was evaluated with the use of the multiple regression models. RESULTS There were 6917 participants, with a response rate of 64%. A lower risk for hot flushes was related to older age, high education, and vigorous physical exercise. The major risk factors for vasomotor complaints were current weight gain, part-time employment, oophorectomy, unhealthy lifestyle, and concomitant health problems. Light smoking, late age of menopause, higher education, and excessive weight reduced the risk of vaginal dryness. However, older age, marriage, and chronic diseases negatively affected vaginal complaints. The background factors had less impact on symptoms in women who used hormone replacement therapy. CONCLUSION Sociodemographic characteristics, lifestyle, and concomitant health problems appear to be important modifiable determinants for menopause-related symptoms.

Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis

Background.  The aim was to evaluate whether patients with benign ovarian cysts, functional ovarian cysts, or endometriosis have an increased risk of developing gynecologic cancer.

Robot assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy with short and long term morbidity data.

OBJECTIVE To evaluate feasibility and morbidity of robot assisted laparoscopic radical hysterectomy. METHODS From December 2005 to September 2008 robot assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy was performed on 80 women. Using a prospective protocol, and an active investigation policy for defined adverse events, perioperative, short and long term data were obtained. RESULTS Time for surgery (skin to skin) reached 176 and 132 min after 9 and 34 procedures respectively. All tumours were radically removed. Median number of retrieved lymph nodes was 26 (range 15-55). All women had an early follow up (1-3 months) and 43 of eligible 46 women (93%) had a long term follow up (> or =12 months). In 33 of 80 women (41%) the peri/postoperative period was uneventful. The remainder had one or more mainly mild adverse events, most commonly from the vaginal cuff (n=17, 21%) or the lymphatic system (n=16, 20%). The proportion of uneventful cases increased significantly over time. Five women were resutured for dehiscence of the vaginal cuff, two women were reoperated for trocar site hernias and one woman had a ureter stricture that resolved following stent treatment. Eight women (14%) needed 60 days or more to resume spontaneous voiding. One 72-year old woman with disseminated endometrial cancer on autopsy died of pulmonary embolism 31 days after surgery. CONCLUSIONS Robot assisted laparoscopic radical hysterectomy is a feasible alternative to conventional laparoscopy and open surgery. Effort should be made to ensure proper closure of the vaginal cuff, trocar sites and to develop nerve sparing techniques.

Transvaginal ultrasonographic findings in the uterus and the endometrium: Low prevalence of leiomyoma in a random sample of women age 25-40 years

Background. In articles and textbooks the prevalence of uterine leiomyomas is said to be 20–25% in women over the age of 30. The aim of this study was to investigate the rate of uterine leiomyoma, the thickness and the texture of the endometrium, and the size of the uterus in a random sample of asymptomatic women 25–40 years old.

The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm.

OBJECTIVE The aim of the study was to evaluate the sentinel node (SLN) concept for lymphatic mapping in early stage cervical cancer. METHODS 105 women with early stage (1a1-2a) cervical cancer were scheduled for the sentinel node procedure in conjunction with a complete pelvic lymphadenectomy. The day before surgery, 1-1.5 mL 120MBq Tc(99) albumin nanocolloid was injected submucosally at four points around the tumor followed by a lymphoscintigram (LSG) to achieve an overview of the radiotracer uptake. RESULTS During surgery, the overall detection rate (gamma probe) of at least one SLN was 90% (94/105 women) whereas at least one SLN was identified in 94% (61/65 women) with a tumor <or=2 cm. Bilateral SLNs were identified in 62/105 (59%) of the women. Among 18 women with any metastatic lymph node 17 had a metastatic SLN (sensitivity 94%, 95% CI 73-100%). Among 61 women with a tumor <or=2 cm, all five women with any metastatic lymph node also had a metastatic SLN (sensitivity 100%). One woman with a 1.5-cm squamous epithelial carcinoma had metastatic positive SLNs on each side but also one metastatic bulky (>2 cm) node without radiotracer uptake. The negative predictive value for patients with cervical cancers <or=2 cm was 100%. CONCLUSIONS The SLN-technique seems to be an accurate method for identifying lymph node metastases in cervical cancer patients with tumors of 2 cm or smaller. In case of a unilateral SLN only, a complete lymphadenectomy should be performed on the radionegative side. All bulky nodes must be removed.

Cleaved Forms of the Urokinase Plasminogen Activator Receptor in Plasma Have Diagnostic Potential and Predict Postoperative Survival in Patients with Ovarian Cancer

Purpose: To evaluate the plasma level of different forms of soluble urokinase plasminogen activator receptor (suPAR) as discriminators between malignant, borderline, and benign ovarian tumors and as prognostic markers in patients with ovarian cancer. Experimental Design: The different suPAR forms were measured in preoperative plasma samples obtained from 335 patients with adnexal lesions using three different time-resolved fluoresence assays (TR-FIA): TR-FIA 1 measuring intact suPAR, suPAR(I-III), TR-FIA 2 measuring the total amount of suPAR(I-III) and the cleaved form, suPAR(II-III), and TR-FIA 3 measuring the liberated uPAR(I). Tumors were classified as benign (n = 211), borderline (possibly malignant; n = 30), and well (n = 19), moderately (n = 15), and poorly (n = 60) differentiated malignant. Results: All uPAR forms as well as CA125 were statistically significant in univariate analysis discriminating between benign, borderline, and invasive tumors. Restricting the analysis of invasive tumors to early stage (I and II) showed similar results. A combination of CA125 and suPAR(I-III) + suPAR(II-III) discriminated between malignant (all stages) and benign tumors [AUC, 0.94; 95% confidence interval (95% CI), 0.90-0.98] as well as borderline and benign tumors (AUC, 0.78; 95% CI, 0.67-0.89). All suPAR forms were markers for poor prognosis in univariate analyses, and high preoperative plasma level of uPAR(I) is an independent predictor of poor prognosis (hazard ratio, 1.84; 95% CI, 1.15-2.95; P = 0.011) in multivariate analyses including age and CA125. Conclusions: High concentration of plasma uPAR(I) is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The combination of plasma suPAR(I-III) + suPAR(II-III) and CA125 discriminates between malignant and benign tumors with an AUC of 0.94.

Reproducibility and accuracy of robot-assisted laparoscopic fertility sparing radical trachelectomy.

OBJECTIVE To assess the accuracy and reproducibility of robot-assisted laparoscopic abdominal fertility sparing radical trachelectomy in women with early stage cervical cancer. METHODS Relevant prospective clinical data from 13 consecutive women planned for robotic radical trachelectomy between 2007 and 2012 were compared with retrospective data from 12 consecutive women planned for vaginal radical trachelectomy between 2000 and 2007. The first follow up on all women included a similar vaginal ultrasonographic measurement of the remaining cervical length and the position of the cerclage, enabling a direct comparison. Peri- and postoperative clinical data were evaluated. RESULTS The remaining cervical length was equal between the robotic and vaginal procedures (mean 11 mm, range 8-13 mm; mean 11 mm, range 5-19 mm respectively, p=0.92). The distance from the cerclage to the inner cervical os was significantly shorter and less variable in the robot group (robot mean 2mm, range of 1-4mm, vaginal mean 4mm, range 2-7 mm, p=0.003). Rejection of the cerclage (n=3) and/or cervical stenosis (n=3) was diagnosed in four women, all of whom in the vaginal group, between one and 13 months after surgery. CONCLUSIONS Robotic trachelectomy is equally reproducible and accurate as the vaginal trachelectomy in terms of the remaining cervical length and results in a significantly more precise placement of the cerclage.

Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI‐1)

The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well‐differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI‐1) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts. The mRNA expressing cells in the in situ hybridization sections were evaluated and counted by two different observers. The number of mRNA expressing cells for uPA, uPAR and PAI‐1 were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI‐1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI‐1 genes in the solid tumors suggest a correlation with a more aggressive phenotype.

Low-dose hormone therapy and carbohydrate metabolism.

OBJECTIVE To evaluate the influence by two low doses of oral continuous-combined formulations of 17 beta-estradiol (E(2)) and norethisterone acetate (NETA) on carbohydrate metabolism in healthy postmenopausal women. DESIGN A double-blind, randomized, placebo-controlled trial. SETTING Volunteers at a university hospital. SUBJECT One hundred twenty healthy postmenopausal women. INTERVENTION(S) One hundred twenty women were randomized to three treatment arms: (1) E(2) 1 mg/NETA 0.25 mg group (n = 40); (2) E(2) 1 mg/NETA 0.5 mg group (n = 40); (3) placebo group (n = 40). A total of 102 women completed 12 months of treatment. An oral glucose tolerance test (OGTT) was performed at baseline and at 3, 6, and 12 months. MAIN OUTCOME MEASURE(S) Fasting glucose, fasting insulin, total area under the curve (AUC) and insulin/glucose index during OGTT. RESULT(S) Fasting levels of glucose and insulin declined significantly in the E(2)/NETA 0.5 mg group. At OGTT, the total AUC for insulin declined in both active arms. The curve for glucose increased significantly in the E(2)/NETA 0.25 mg group. A lower insulin/glucose index was observed during OGTT in both active regimens when compared with placebo. In the active treatment groups, a significant reduction of fasting glucose and/or fasting insulin was encountered in women with higher basal fasting levels (fasting glucose >4.2 mmol/L or log-fasting insulin >0.87). CONCLUSION(S) Oral low-dose E(2) 1 mg/NETA 0.5 mg regimen did not impair carbohydrate metabolism, but seemed to improve insulin sensitivity in healthy postmenopausal women.

High preoperative blood levels of HE4 predicts poor prognosis in patients with ovarian cancer

AbstractThe aim of this study was to assess the clinical value of preoperative blood levels of HE4 as a predictor of overall survival in patients with ovarian cancer and to validate previous data of HE4 and the ROMA algorithm including HE4 and CA125 in discriminating benign and malignant ovarian tumors.Experimental designThe preoperative plasma levels of HE4 and CA125 were analyzed with ELISA in 312 patients with adnexal lesions. Tumors were classified as benign (n= 206), borderline (i.e. low malignant potential tumors) (n= 25), and well (n= 14), moderately (n= 15), and poorly (n= 51) differentiated malignant.ResultsIn univariate Cox regression analyses high levels (dichotomized at the median) of HE4, CA125, increased age (continuous variable), advanced-stage of disease 2–4, histological grade 3 and non-optimal tumor debulking at primary surgery were all significantly associated with shorter overall survival. A multivariate Cox regression model including pre-operative available covariates HE4 and CA125 both dichotomized at median in addition to age as continuous variable showed that high levels of HE4 was an independent prognostic marker for worse prognosis HR 2.02 (95% CI 1.1-3.8). In postmenopausal women the ROMA algorithm gave the highest AUC of 0.94 (95% CI, 0.90-0.97) which was higher than the separate markers HE4 AUC 0.91 (95% CI 0.86-0.95) and CA125 AUC 0.91(95% CI 0.87-0.96).ConclusionsHigh concentration of plasma HE4 is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The algorithm ROMA discriminates in postmenopausal women between malignant and benign tumors with an AUC of 0.94.