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

The 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 design: The 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. Results: In 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). Conclusions: High 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

Ovarian tumors. Prevalence, malignancy risk and significance of the Plasminogen activation system.

The aims were to assess the prevalence of ovarian tumors in fertile asymptomatic women and to evaluate the risk of ovarian cancer in women with a history of benign ovarian tumors and endometriosis. In order to search for biomarkers in ovarian tumors, the plasminogen activating (PA) system was studied. A random sample of women 25-40 years old was invited to a transvaginal ultrasonography examination. Ovarian cysts were found in 7% (22/335). At follow-up three months later 18 of the 22 cysts had spontaneously disappeared. In a case-control study, The Swedish Hospital Discharge Register, The National Swedish Cancer Register, and the Fertility Register, were used to analyze the risk of developing ovarian cancer in women hospitalized with the diagnoses of ovarian cyst, functional ovarian cyst, or endometriosis. Young women (15 to 29 years old) discharged from hospital for ovarian cysts and functional cysts showed a doubled risk of developing ovarian cancer. Women with ovarian cysts who had undergone ovarian cyst resection or unilateral oophorectomy had a nine times higher risk of developing ovarian cancer. Women with endometriosis had a minor increased risk of ovarian malignancy. The risk of developing ovarian cancer was inversely related to parity and the mean age at diagnosis of ovarian cancer was lower in all three study groups as compared with the control groups. The gene expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and inhibitor (PAI-1) was increased in malignant as compared with benign tumors, and also increased in poorly as compared with well-differentiated malignant tumors. All three mRNA species were mainly found in the stroma in poorly differentiated tumors and metastases. Stromal expression may be induced by the tumor cells. The protein levels of uPA, uPAR, uPA:PAI-1 complex were higher in malignant than in benign ovarian tumors. Furthermore, the protein content of uPA, uPA:PAI-1 complex and also PAI-1 was higher in poorly than in well-differentiated tumors. In contrast, the level of uPAR was lower in poorly than in well-differentiated malignant tumors, and also lower in advanced than in early stages of the disease. This discrepancy may be the result of increased turn-over of uPAR in poorly differentiated tumors. High tumor tissue content of uPAR as well as low content of uPA was associated with longer postoperative survival

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. Methods. The Swedish Hospital Discharge Register was used to identify a cohort of women discharged from hospital with the diagnoses of ovarian cyst (n = 42 217), functional ovarian cyst (n = 17 998), or endometriosis (n = 28 163). To each case, three controls were matched. The National Swedish Cancer Register matched all incident cancers diagnosed among cases and controls. From the Fertility Register, the date of birth of children born to the cases and controls were obtained. Results. Women with endometriosis had an increased risk for ovarian cancer (OR 1.34; 95% CI 1.03-1.75), but no association was found between ovarian cysts or functional cysts and ovarian malignancy, including all ages. Young women (15-29 years old) discharged from hospital for ovarian cysts and functional cysts showed an increased risk of developing ovarian cancer later in life (OR 2.2; 95% CI 1.3-3.9 and OR 1.8; 95% CI 1.5-2.0), as well as women with ovarian cysts who had undergone ovarian cyst resection or unilateral oophorectomy (OR 8.8; 95% CI 5.2-15). The risk of developing ovarian cancer was inversely related to parity. Mean age at diagnosis was significantly lower in all three study groups. Conclusion. In this study women with endometriosis and young women who had undergone surgery with removal of an ovarian cyst had an increased risk of developing ovarian cancer

Increased HPV detection by the use of a pre-heating step on vaginal self-samples analysed by Aptima HPV assay

Background: We recently reported a sensitivity of 85.5% to detect high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer by the use of self-collected vaginal samples analysed by the Aptima mRNA HPV assay (AHPV). Objectives: To increase detection of HPV among self-samples. Study design: We used a pre-heating step at 90 °C for 1 h on our previously AHPV-negative self-samples (N = 20) among women with AHPV-positive cervical samples. We also analysed AHPV results before and after the heating among a series of self-samples from women who had not attended cervical screening for > 7 years (N = 173). Results: After heating, 55% (11/20) of the self-samples became AHPV-positive. By updating our original series 93.1% (121/130, 95% CI: 87.3–96.8) of the self-samples were AHPV-positive among women with AHPV-positive cervical samples, and among women with histologically confirmed cervical intraepithelial neoplasia or worse (CIN2+) now 95.3% (61/64, 95% CI: 86.9–99.0) of the self-samples were AHPV-positive. Among the 11 AHPV-positive self-samples we detected high-risk HPV types in 10 of the samples (HPV16 3 cases, HPV18 1, HPV31 1, HPV33 1, HPV 45 1, HPV51 2, HPV 56 and 58 1, HPV42 and 90 1 [low risk]) by multiplex PCR and Luminex assay. Among the self-samples from the non-attenders 16% (27/170) and 5.3% (8/152) were AHPV-positive after and before the heating step, respectively (P = 0.0022). Concerning validity of AHPV-results, 99% (170/172) were valid after the heating step compared to 88% (152/172) before the heating step (P < 0.0001). Conclusions: A pre-heating step on vaginal self-samples increased HPV detection by the AHPV assay

Fertility-sparing surgery and outcome in fertile women with ovarian borderline tumors and epithelial invasive ovarian cancer.

Objective: The aim was to evaluate the outcome of fertility-sparing treatment in ovarian borderline tumors and early invasive ovarian cancer. Materials and methods: All women diagnosed with an ovarian borderline tumor or early invasive ovarian cancer who were treated with fertility-sparing surgery at the University Hospital in Lund between 1988 and 2002 were identified and included in the study (n = 23). Results: During the follow-up period of a median 92 months, range 11-185 months, no relapse was found in the patients with Stage 1a tumors, including both borderline tumors (n = 12) and invasive well-differentiated (n = 9) and moderately differentiated (n = 1) ovarian cancers. One patient with poorly differentiated ovarian cancer Stage 1c was 13 weeks' pregnant at the time of the primary operation. Although, unilateral oophorectomy was performed she insisted on continuing the pregnancy. At 37 weeks she had a cesarean section and the ovarian cancer was disseminated. Chemotherapy was given but she died less than a year later. None of the other patients received chemotherapy. In total, 30 children were born to 15 patients. Prophylactic removal of the remaining ovary hysterectomy was accepted in only in six of the women after fulfilling their desire to have more children. Conclusions: Young women with Stage 1a epithelial ovarian cancer and borderline tumors do not have to give up their fertility in order to receive successful and safe treatment of their disease. However, several of these patients do not accept the recommendation of prophylactic oophorectomy of the contralateral ovary and hysterectomy after completion of childbearing. (C) 2006 Elsevier Ireland Ltd. All rights reserved

Background factors influencing somatic and psychological symptoms in middle-age women with different hormonal status A population-based study of Swedish women.

Objective: To analyse the influence of socio-demographic characteristics and environmental factors on self-reported somatic and psychological symptoms among middle-aged Swedish women. Methods: A total of 6917 women living in the Lund area of southern Sweden were participates of this study. They completed a generic questionnaire pertaining to socio-demographic characteristics, lifestyle factors and current health related problems. According to hormonal status, the participants were subdivided into three groups, i.e. premenopause, postmenopause and perior postmenopausal women with hormone replacement therapy (HRT). Results: By using multiple logistic regression models, a high risk for somatic symptoms was independently associated with unemployment, no exercise, unmarried, high body weight and diseases affecting the cardiovascular system as well as a history of cancer. Psychological symptoms were independently associated with higher educational level, unemployment, no exercise, unmarried, heavy smoking habits (>= 15 cig/day), weight gain and a history of cancer. In addition, the background factors seemed to have less impact on symptoms among women who used HRT. Conclusion: Socio-demographic characteristics, lifestyle factors and concurrent health problems appear to have influences on the frequency and the number of somatic and psychological symptoms in middle-age women. Hormone replacement therapy seems to be able to counteract negative impacts caused by un-healthy lifestyle and other health problems